Hi friends,

Well, once again, a very quiet news week (as it should be, these last few weeks of August are the right time to check out) and I’ll be taking next week off from the newsletter :)

For today, no news worth sharing, so I am digging into a condition that affects an enormous number of women and has become one of the more active conversations around using GLP-1s as a supporting tool. I wanted to understand whether this is actually treating the root cause, and why it seems to help some people and not others.

🚫 Is insulin the root of PMOS?

For years I have been hearing about this condition from friends, usually some version of it took forever to get diagnosed and nobody can explain it to me.

It is not something I have. Looking into it, the numbers are wild: it affects about one in eight women, more than 170 million worldwide, most of them from their late teens into their forties, and the WHO estimates roughly 70 percent do not know they have it.

It also just got a new name, because the old one was pointing at the wrong thing. In May, polycystic ovary syndrome was reclassified as polyendocrine metabolic ovarian syndrome, or PMOS, since the condition is not really about cysts. Shocking that we were not paying closer attention to women’s health…

Diagnosis requires two of three things: irregular or absent ovulation, high androgens (the hormones behind acne, unwanted hair growth and thinning hair), and a particular ovarian appearance on ultrasound.

Why it keeps coming up in the GLP-1 conversation

Insulin resistance shows up in roughly 70 to 80 percent of cases. Excess insulin pushes the ovaries to overproduce androgens, and those androgens drive the irregular cycles, the skin and hair changes, and the stubborn weight.

Most of what women are offered treats the end of that chain. GLP-1s act on the insulin, nearer the start of it.

So is insulin the root?

No, but it is a huge driver, and it is the part we can now do something about.

Here is the thing that surprised me. With type 2 diabetes, insulin resistance is often driven by carrying extra weight, which is why losing weight can improve it so dramatically. PMOS does not work that way. Lean women with PMOS have insulin resistance too, to a degree comparable with heavier women, driven by differences in insulin signaling rather than by body fat.

It is also not a clean starting point. Insulin drives androgen production, and androgens feed back and worsen insulin resistance. It is a loop, and researchers rarely see one side of it without the other already present, which makes the order genuinely hard to establish.

So a GLP-1 interrupts the loop at one point. It does not switch it off, and it does not fix whatever started it.

TLDR: it works on a real mechanism, further upstream than most existing options, and still downstream of the actual cause.

What is actually available to treat PMOS?

Nothing. Which is exactly why a LOT of eyes are on GLP-1s to help

There are no FDA-approved medications for this condition. Every drug prescribed for it is already off-label. The international guideline, written by a global network led out of Monash, puts combined oral contraceptives first-line for irregular cycles and high androgens, and metformin primarily for the metabolic side. Spironolactone gets used off-label for acne and hair growth. Letrozole gets used to induce ovulation. The same guideline grades the overall evidence base in this condition as low to moderate quality.

So: one in eight women, no approved treatment, and a first-line option that manages symptoms without touching the metabolic driver.

That is the context for what is happening now. I wrote about a version of this a few weeks ago with addiction. Where the existing options are thin and the need is enormous, a drug showing a real signal gets adopted well ahead of the evidence. The difference here is that the mechanism is not speculative. It is insulin, and these drugs work on insulin.

Which does not make it settled

No GLP-1 is approved for PMOS. There is no dedicated randomized trial of tirzepatide in this population at all. What exists is off-label prescribing built on the mechanism and a set of small studies, which is informed improvisation rather than established care.

And every randomized trial in this population enrolled women with obesity. Not overweight, obesity, with average BMIs in the mid-thirties. The meta-analysis of randomized trials is titled for women living with obesity. The study showing 80 percent of responsive patients had cycles normalize enrolled women with a mean BMI of 34.4 who had not responded to a lifestyle program.

There is no trial of a GLP-1 in leaner women with PMOS.

There is also a reason to pause before handing this to everyone with the diagnosis. Eric Ravussin at Pennington, one of the researchers in the ongoing argument about muscle loss on these drugs, names low BMI specifically as a group warranting caution. Across trials, 12 to 40 percent of weight lost on semaglutide is lean tissue, with some reductions in hip and spine bone density. With weight to lose, that tradeoff usually favors treatment. Without it, the arithmetic changes, and nobody has run that study…yet

And then there’s the coverage wrinkle…

If a woman with PMOS also meets the obesity criteria, she gets the drug on-label for obesity and the hormonal improvements come along with it. If she has the identical condition at a lower weight, prescribing for PMOS is off-label, and insurers routinely deny it.

Same woman, same disease, different paperwork.

Mihail Zilbermint, who directs endocrine hospitalists at Johns Hopkins Community Physicians, calls the condition complex precisely because it presents so differently person to person.

A big thing to know linked to another headline…when PMOS improves, cycles often come back and ovulation restarts. For many women that is the entire point.

It is also, almost certainly, a meaningful contributor to the Ozempic babies phenomenon (covered in a post a few weeks back). If a GLP-1 is fixing what was broken, fertility may return before anything else about the plan does.

Have a topic you want me to dig into next month? I’d love to hear it.

See you all after Labor Day!

Helaine

Important reminder: I am not a doctor. This is one person’s reporting and experience, not medical advice. Talk to yours before you change anything.

Who am I? Helaine Knapp is the founder of CityRow, a fitness company she built and scaled for a decade before selling in 2024. She is also the author of Making Waves, host of the Step Into Next podcast, and an executive advisor and coach working with founders and leadership teams navigating growth and transition. She has been on her own GLP-1 journey for nearly two years and is building something for everyone navigating this one.

helaineknapp.com · Substack

Making sense of the chaos, together.

Hi friends,

It is the middle of August and the news cycle feels like the middle of August. Two things I read this week, and then something I have been sitting with personally for a while, which turns out a lot of my friends (and the internet) are sitting with too.

📚 Two Things I Read This Week

1. Yale researchers found that semaglutide activates the brain’s hunger neurons rather than quieting them, and in mice engineered without those neurons the drug could not sustain weight loss. The hunger circuitry is not what the drug defeats. It is part of how the drug works. Which means feeling hungry is not good evidence that your dose is too low. Published in PNAS, in mice, which the authors say plainly.

2. A separate Yale team asked whether starting a GLP-1 helps people with type 2 diabetes get off insulin. They compared people who started a GLP-1 against people who started one of two other classes of diabetes drug, SGLT-2 inhibitors or DPP-4 inhibitors, across 9,000 matched pairs over three years. All three groups came off insulin at about the same rate. The GLP-1 was not the differentiator. The lead author’s conclusion was that nobody has a protocol for stopping insulin at all.

🚫 Myth I want to bust: the maintenance conversation

You don’t have to go far to get dozens of different answers to the same question - how are people approaching maintenance after weight loss on GLP-1s?

Some people stay at the highest dose they reached. Some drop down a level. Some taper off completely. Some microdose. Some stretch the interval out. And then there’s infinite combinations of the prior.

When I wrote about coming off these drugs in April, the thing that came through was that stopping is not one decision, it is a set of them made over months. Maintenance is not what happens afterward. It is the same calculation asked at a different time. What dose, how often, for how long, what happens if I go lower or off completely?

When I ran a survey earlier this year, this came up unprompted more than once. One woman wrote that she wanted “more guidance on how to lower dosage for maintenance.” Another described exactly the situation perfectly: she assumed she could come off and be fine, learned she needed to stay on for maintenance, then her provider’s prices went, in her words, crazy expensive, and she has been flip-flopping between providers ever since without clearly knowing what her dose should be. She finished with: “I hate having to go to the doctor every single time I need to do something like this. It’s a waste of my time. And the money grab.”

Let’s start with the money, because it shapes the advice

Every business in this category is running a lifetime value calculation on you. Not in a sinister way, that is just what businesses do. But when the evidence is thin, LTV fills the gap, and it is worth knowing which direction it pushes.

Start with the manufacturer. Under Lilly’s self-pay program, Zepbound runs $299 at 2.5 mg, $399 at 5 mg, and $449 for everything from 7.5 up, provided you refill within 45 days. So the price climbs off the bottom and then flattens. Nobody at Lilly or the prescriber for it wants you sitting on 2.5 or 5, which are the cheapest rungs, and the whole titration structure moves you past them. Once you are at 7.5 or above you are in the tier they want, and from there what is being monetized is not your dose. It is your continuity.

The dose-escalating incentive sits one layer down, with the med spas and telehealth platforms that resell this. Their pricing climbs with every step, and the industry writes about it openly. One professional guide describes the maintenance phase as the backbone of a recurring-revenue weight loss program, sold alongside a protocol kit. A customer who steps down is a smaller customer. A customer who comes off is a churned one.

Which is why the automatic titration schedules bother me. Plenty of platforms move people up on a calendar rather than a conversation, and I have watched it happen to friends. The unspoken assumption is that higher is the destination and you are just working your way there.

But that assumption does not hold for everyone. One woman wrote that she lost 62 pounds in 41 weeks on 2.5 mg, the starting dose, and is no longer pre-diabetic or hypertensive. She would go lower if a lower dose existed. She describes herself as a super-responder and says she knows there are others, because she has read their posts. Her argument is the best one in this whole piece: the studies give averages and generalizations, and they do not speak to the individual.

For some people the lowest dose is enough to take the edge off and get where they were going. Nothing in the business model is set up to notice that.

Compounders sometimes want the opposite answer, because splitting doses is how you sell a cheaper product to someone priced out of the brand. So the loudest advocates for going lower have a position too.

Insurers, for now, until true long-term incentives are aligned for health and longevity, want you off it entirely, and people often ask how that reaches them, since most of us never speak to our insurer. It arrives as friction. Prior authorization on a dose change. Reauthorization paperwork every year. Quantity limits. And plan documents that change quietly in the fall, which is how 19 percent of employers who now cover these drugs for diabetes only used to cover them for weight loss and stopped. There is also a wrinkle worth knowing: Zepbound’s label names 5, 10 and 15 mg as maintenance doses, because those were the arms in the original trial. The 7.5 and 12.5 doses exist as titration steps. Some insurers read that literally.

None of these parties is neutral. The evidence is thin enough that all of them can sound reasonable, which means you will probably have to advocate for yourself here.

Now the one real trial on maintenance

SURMOUNT-MAINTAIN published online in The Lancet on May 12 and in print on June 6, after the initial results were presented at the European Congress on Obesity. It is the first randomized trial to test this question directly, and it landed after the last time I wrote about any of this.

441 people took tirzepatide for 60 weeks up to their maximum tolerated dose of 10 or 15 mg. Then 378 were randomized for another 52 weeks to stay there, drop to 5 mg, or switch to placebo. Sixty-five percent of participants were women.

At week 112, change from starting weight:

• Stayed at max dose: down 21.9 percent

• Dropped to 5 mg: down 16.6 percent

• Placebo: down 9.9 percent

Read quickly, that says dropping down costs you a few points and is basically fine. Then look at the individual level. Among people who had reached a weight plateau, the share who held onto at least 80 percent of what they had lost was 77.5 percent of those who stayed at their max dose, 42.4 percent of those who dropped to 5 mg, and 10.4 percent on placebo.

That is the number I keep thinking about. The averages are four points apart. The odds of it working for you personally are nearly cut in half.

Deborah Horn at UTHealth Houston, who led the trial, said it addresses the number one question she gets from patients who have responded well: do I need to stay on this dose, could I go lower and keep it off, could I stop.

TLDR: staying works for about three in four. Dropping to 5 mg works for about two in five. Stopping works for one in ten. The mean hides all of that.

Which is more than we had, and still not enough

Three months ago there was no randomized answer at all. Now there is one, for one drug, testing one step-down.

It did not study cycling, splitting pens, any step-down other than 5 mg, or anyone maintaining at 2.5, 7.5 or 12.5. It ran at 20 US sites in a mostly white population, and did not look at anyone on hormone therapy.

On stretching the interval, which I dug into back in May, there is now one piece of human evidence. Researchers at Scripps published a case series in Obesity in February on patients who moved to less frequent dosing at below-maximum doses after hitting a plateau. Those patients generally held their weight and their metabolic markers. Retrospective and small, so a signal rather than an answer. The line that stayed with me is the authors’ own: no evidence-based protocol exists for stepping down, and patients are already rationing and experimenting on their own.

And there is now a third path that did not exist as a real option a year ago. In a trial reported in May, adults who switched from high-dose injections to the oral pill kept most of their earlier weight loss over a year. That reframes the whole question. Maintenance might not be a dose decision at all. It might be a format decision.

One thing if you take semaglutide rather than tirzepatide: the cardiovascular benefit was demonstrated at 2.4 mg, and going below that has never been studied for heart outcomes. Someone dropping their dose to afford it may be giving up the reason they were prescribed it.

What doctors without a product say

The Obesity Medicine Association’s Access and Policy Working Group: there is little to no peer-reviewed evidence supporting the safety or effectiveness of microdosed regimens for obesity.

Disha Narang, who directs obesity medicine at Endeavor Health in Chicago, holds both halves: understanding long-term dosing and cost stewardship is essential, and the early data on stepping down is not enough to change practice broadly. She reported no relevant conflicts.

Susan Wolver at VCU Health adds the detail that changes the downside math: weight regained is primarily fat rather than lean mass. Going backward does not return you to where you started. (key point on why protein + strength training is so critical!)

TLDR: lowering your dose is a reasonable individual experiment. Nobody should be calling it standard care yet.

What people are actually doing

The most detailed conversation on this is not in a journal. It is in comment threads.

One woman described cycling, lowering her dose for a few weeks then raising it for a few weeks on repeat, because at a lower dose her inflammation comes back after a couple of months. Her ask was simple and nobody has answered it: she wants data on whether microdosing works for people in maintenance.

Another described dividing a 15 mg dose into three 5 mg doses taken Monday, Wednesday and Friday, to reduce side effects rather than to save money.

And a correction from those threads that is more precise than most published coverage: microdosing, split dosing and divided dosing are three different things, and people use them interchangeably. The vocabulary came from influencers, not from medicine.

Where I have landed

I take 7.5 mg of tirzepatide and I have been there, unchanged, for about two years. Nobody has ever asked me about it. Personally, I never followed up with the doctor who first prescribed it, and I get my prescription through One Medical now, where it has never come up as a question about what’s next…

For now, I am staying at 7.5 because it is working and nobody is pushing me either way. If that changes, I will make sure I understand the incentives of whoever I'm talking to before I make any decisions.

See you next week.

Helaine

____

Important reminder: I am not a doctor. This is reporting and experience, not medical advice. Talk to yours before you change anything.

Making sense of the chaos, together.

Hi friends,

Happy Tuesday and welcome back to breaking down all the things.

What’s inside: what one bank’s $250 million says about your own coverage, and whether these drugs quietly turn down your drive.

📚 Three Things I Read This Week

1. Penn Engineering ran AI over 400,000 Reddit posts from 70,000 GLP-1 users, published in Nature Health. Forty-four percent reported a side effect. The two that stood out: irregular cycles, and temperature problems like chills and hot flashes. About 4 percent reported menstrual irregularities, which would be higher in a female-only sample.

2. Bank of America spends over $250 million a year on GLP-1s for 211,000 employees. That is 13 percent of its entire employee health budget, up from zero five years ago.

3. An NBER paper tracked Danish workers on Ozempic: 17.3 percent less long-term sick leave over four years. No change in employment or earnings. Fewer sick days, same paycheck.

💰 What the money is doing

As linked above, Bank of America made news last week for spending over $250 million a year on GLP-1s for its 211,000 employees. It is real money, and it is also a recruiting tool: 29 percent of employees say they would change jobs for GLP-1 coverage. Employees still pay their premium and copay.

It made news because almost no one else is doing it.

The headline number says coverage is stable. It is not.

• 36 percent of employers cover GLP-1s for both diabetes and weight loss, unchanged from 2025.

• That number is flat because employers are dropping coverage at about the same rate others add it. Nineteen percent of employers who now cover diabetes only used to cover weight loss and stopped.

• Of the employers not covering weight loss, 62 percent will not consider adding it and 83 percent have carved it out of their plans.

• Cigna dropped it in its own employee plan in July. nHCA dropped it in January. About 11 percent of large employers have dropped or plan to drop it this year or next.

• The reason is cost. GLP-1s went from 6.9 percent of employer health claims in 2023 to 11.4 percent in 2026.

If your plan covers your prescription today, that is not a promise about next year. Open enrollment is in the fall. Pull your 2027 plan documents when they land and read the pharmacy section before you re-enroll.

📊 And at the drugmakers

Both reported earnings last week and told the same story from opposite sides. Lilly’s revenue rose 48 percent on a 60 percent jump in volume, even as what it collects per prescription fell. Novo now reaches 46.5 million people with its obesity and diabetes drugs, with US injectable Wegovy sales down 22 percent on lower prices while volumes rose. More people, less money per person. Your employer’s bill still goes up, because it is paying for more people, not a higher price each.

One thing worth marking on your calendar: Novo has said that effective January 1, 2027, it will cut the US list price of Wegovy injection and tablets, and Ozempic, to $675. That is roughly half the current Wegovy list price.

🔬 One study worth knowing about

Penn, Yale and UT Southwestern pooled 19 randomized trials covering 13,117 people and ranked GLP-1s across seven measures at once: weight, waist, HbA1c, blood pressure, triglycerides, HDL and LDL. Senior author Yong Chen’s takeaway is that there may be no single best GLP-1, and it depends on your goals.

The catch: it only included mono-agonists, so semaglutide, liraglutide and orforglipron. Tirzepatide was excluded, meaning it says nothing about Zepbound or Mounjaro. And the ranking system is one the authors built for this paper, not a validated tool. Guidance has not changed. But if you are on one of these for cholesterol or blood pressure as much as for weight, which drug you take may matter more than assumed.

🚫 Myth I want to bust: GLP-1s flatten your drive

At breakfast last week a friend asked whether, side effect wise, I felt like I had less drive.

I laughed. I said absolutely not. I am one of the most driven people I know.

Then I thought about it for the rest of the day.

The clinical word is anhedonia, a reduced ability to feel pleasure. Not low mood, and not a smaller appetite. People describe losing interest in hobbies, sex, socializing. Online it gets called Ozempic personality, which is not a clinical anything. I touched on it in throughout an article I wrote May. Here is what has been measured since.

How common is it? Nobody knows. It was never measured in the trials and is not on the label for Ozempic, Wegovy, Mounjaro or Zepbound. Clinicians tracking it say it is uncommon and that far more patients report the opposite. One physician described a patient saying it felt like the lights had dimmed, but she could not say why.

The mechanism is plausible. GLP-1 receptors sit in the brain’s reward circuitry, and those structures do not sort desire into categories. Turn down the one that wants food and you may be turning down the one that wants everything.

The one trial that tested it found the opposite. JAMA Psychiatry, April 29. Seventy-two people with depression and a BMI of 25 or higher, 14 mg oral semaglutide or placebo, 16 weeks, measuring how hard someone will work for a reward. The semaglutide group worked harder, not less.

But it did not measure the thing people are describing. Ciara McCabe at Reading made the point that matters: the study is small and contains no anhedonia assessment at all. It measured motivation, which is related but different. Two authors disclosed pharmaceutical industry ties. No trial has ever measured emotional blunting on a GLP-1 with a validated anhedonia instrument.

On sexual desire, the data runs both ways. A Kinsey survey found 18 percent said desire increased and 16 percent said it decreased. I am not leaning on it: single adults only, dating-framed, self-reported once. The FDA’s adverse event database logged 182 GLP-1 sexual adverse events between 2003 and 2024, a weak signal, mostly men.

And the two things I keep having to say. Every study here is semaglutide. There is no randomized data on tirzepatide or retatrutide and drive or anhedonia. The literature on women is close to nonexistent: the strongest published evidence on GLP-1s and female sexual function is a case report about one 71-year-old woman.

💬 What I’m thinking about

Roughly 30 million Americans now take a GLP-1 for weight loss. Two years ago it was about 8 million. The anecdotes are arriving far faster than the studies, and that is not a knock on the anecdotes. When millions of people start reporting the same thing, something is happening.

I believe the people who say the lights dimmed. I also believe the trial that found the opposite. Both can be true, because this drug does not do the same thing to everyone.

So I laughed at breakfast, then I checked, and the answer is that I am sure some people are really feeling this many, myself included aren’t - that’s common with side effects and I look forward to real studies (with a good amount of women), that tell us more.

Until next week,

Helaine

P.S. Forward this to the friend who asked you something you brushed off and then thought about all day.

Important reminder: I am not a doctor. This is reporting and experience, not medical advice. Talk to yours before you change anything.

Making sense of the chaos, together.

Hi friends,

Happy Tuesday and welcome back to breaking down all the things.

What’s inside: some early pregnancy data worth having, and a full accounting of what GLP-1s do and do not do to addiction.

🤰 Some early data on GLP-1s and early pregnancy

A study led by researchers at the Harvard T.H. Chan School of Public Health, published in Annals of Internal Medicine on June 9, looked at 3,572 pregnancies in women aged 16 to 55 who had filled a GLP-1 prescription in the 90 days before their last menstrual period. It compared the women who continued into the first trimester against the women who stopped, and found no association with pregnancy loss, abnormal fetal growth, or major congenital malformation.

Guidance has not changed. You still stop before trying to conceive, roughly a month out for tirzepatide and about two for semaglutide.

This connects to the fertility question I covered in my July 7th article on the theory of "ozempic babies". These are not fertility drugs, but weight loss can restart ovulation that had stalled, and people get pregnant without planning to. So the situation that comes up is finding out you are pregnant while still on the drug. The early data is trending toward that being okay.

Two limits. The authors said some estimates were imprecise, particularly for the rarer outcomes, and called for more research. And this is claims data covering GLP-1s as a class, so it cannot separate semaglutide from tirzepatide.

📚 Three Things I Read This Week

1. Sanjay Gupta interviewed Dhruv Khullar on Chasing Life on Friday, building on Khullar’s New Yorker reporting on GLP-1s and addiction. Go to 16:09, where they get into what the drugs might be dampening that you did not want dampened. Khullar is bullish on these molecules and says it anyway.

2. BBC Science Focus published the clearest mechanism explainer I have found. The core finding: in rodents, dopamine does not spike after alcohol if you give a GLP-1 first. Lorenzo Leggio at NIH also notes dopamine is not the only route, and that people who drink to relieve stress rather than for pleasure may be responding to something else.

🚫 Myth bust: Ozempic cures addiction

The conversation about GLP-1s and addiction has been going on a long time. I covered it briefly in the May piece on ancillary benefits, "What are these drugs really doing besides the weight loss?", and enough has moved since then that it deserves an update.

Start with what is not in dispute. There is a signal. People on these drugs report drinking less, smoking less, wanting things less. Researchers took it seriously, and there is now a real body of work, which is more than you can say for most things in this space!

The open questions are the good ones. Is the drug acting on addiction itself, or is this a halo effect, where people who are eating less and losing weight and generally in health mode also happen to drink less? How big is the effect? And should these be prescribed for addiction on their own, in people who are not on them for weight or diabetes?

The answer depends on which substance you are asking about. And worth noting that every human trial has been done with semaglutide. Not tirzepatide, not retatrutide.

Alcohol. The only one with serious randomized evidence. A 2022 trial of exenatide, an older GLP-1 from 2005, found nothing overall, though a subgroup with obesity improved. A 2023 trial of dulaglutide, another earlier one, found a 29 percent higher likelihood of reducing intake, in a study that was not about alcohol. A 2025 semaglutide trial in JAMA Psychiatry with 48 people found less craving, fewer heavy drinking days, and less alcohol consumed in a lab session. In April, The Lancet published 108 adults with obesity seeking treatment for alcohol use disorder: 26 weeks, semaglutide against placebo, therapy in both arms, heavy drinking days down 41 percent on the drug against 26 percent on placebo. And on July 29, a Colorado team published 50 heavy drinkers on oral semaglutide for eight weeks who cut their drinks per drinking day in half.

TLDR: This one is real. Semaglutide reduces heavy drinking. Every trial was short, most were small, and nearly all of them were in people who also had obesity.

Nicotine. Thin. An exenatide trial with a nicotine patch produced a risk ratio for quitting of 1.70 with a confidence interval running from 0.96 to 3.27, which means it could be nothing. Dulaglutide did not improve abstinence. In the semaglutide trial, cigarettes per day did not move.

TLDR: Good theory, no proof. If you quit smoking on a GLP-1, the drug may not be why.

Opioids, cocaine, cannabis, meth. No completed randomized human trials. What exists is one large observational study in The BMJ from March, following 606,434 US veterans with type 2 diabetes for up to three years, which found lower rates of new substance use disorders across the board. Hazard ratios of 0.75 for opioids sound dramatic. The absolute difference was about 6.6 fewer cases per 1,000 people over three years. The researchers wrote that their findings do not support prescribing GLP-1s to prevent or treat substance use disorders. Also, VA data, so overwhelmingly men, which sits oddly next to the fact that women are roughly two-thirds of real-world GLP-1 users.

TLDR: One big study, no trials, and the researchers themselves said do not prescribe on this.

Gambling, shopping, scrolling. Nothing. Not a small trial, not a mixed trial. Anecdote plus a plausible reward-circuit story, which is the combination that produces confident wrong headlines.

TLDR: Zero evidence. This is the part of the headline that is fully made up.

Back to the halo. This is what the randomized trials are for. A placebo group is also losing motivation to drink for all the ordinary reasons, so if the drug group drinks less than the placebo group, the halo is not the explanation. Two details make the case stronger. The JAMA Psychiatry trial used 0.25 and 0.5 milligrams for nine weeks, doses and a timeline too low and too short for meaningful weight loss, and still moved drinking. And it measured alcohol consumed in a lab session, which is not a lifestyle outcome. Rodents, who are not in health mode, show the same dopamine effect. So the drug is doing something directly.

How much it is doing is a separate question, and the meta-analyses disagree. Pool only the randomized trials and the alcohol effect is not statistically significant. Pool trials plus observational studies and you get a large result with a heterogeneity score of 87.5 percent, meaning the studies are not measuring the same thing. The real answer is somewhere in between and nobody can tell you where yet.

Two more things. Almost every positive trial studied people who also had obesity or diabetes. Klara Klein at UNC, senior author on the JAMA Psychiatry trial, said there is every reason to be enthusiastic, but these have not been tested in people who do not have overweight, obesity, or type 2 diabetes. That is the standalone question, still unanswered. And nobody has followed anyone after stopping. The longest trial ran six months.

So, the precise version. In people with obesity and alcohol use disorder, semaglutide reduced heavy drinking in short trials, and the effect looks real and not just a halo. Everywhere else there is a mechanism, a mountain of anecdote, and roughly thirty trials still running. The newest and best-designed alcohol trial found people on semaglutide were no more likely to quit drinking than people on placebo. They drank less. They did not stop.

None of this is FDA approved for addiction. Every prescription written for it today is off-label.

💬 What I’m thinking about

The FDA has not approved a new medication for alcohol use disorder since 2006. There are three approved medications for opioid use disorder, total. By one NIH estimate, 98 percent of people with alcohol use disorder never receive any of them.

That is context enough for why so many want this to work so badly.

Until next week,

Helaine

P.S. Forward this to the person who has been quietly wondering whether the drink they stopped wanting was the drug or a coincidence.

Important reminder: I am not a doctor. This is reporting and experience, not medical advice. Talk to yours before you change anything.

Making sense of the chaos, together.

___

I’m Helaine Knapp. I’ve been on a GLP-1 for almost two years and I’m still figuring it out alongside you. I built CityRow before this, sold it in 2024, and started writing because the information in this space is moving faster than anyone can track and women deserve a calmer voice in it. I’m also a coach, advisor, the author of Making Waves and host of the Step Into Next podcast.

Substack is where I write the longer essays. The newsletter, on Beehiiv, is where I land in your inbox every Tuesday morning with what’s actually worth knowing, every week. Get on the list here.

Hi friends,

Happy Tuesday and welcome back to breaking down all the things.

What’s inside: the peptide vote that made me read the same sentences three times, a look at how some stricter countries are handling the same question, and the real story behind fiber taking over your feed.

💉 The peptide vote, and the evidence behind it

Last week an FDA advisory committee voted to recommend six peptides for the compounding list: BPC-157, KPV, TB-500, MOTS-c, Semax, and Epitalon. Only one, a sleep peptide, got voted down. The catch is that the panel voted against the FDA’s own scientists, who had reviewed the research and recommended against all seven. The vote is non-binding, and any real change runs through a rulemaking process into 2027, so nothing is legal or available tomorrow. But if the FDA follows the advice, which it usually does, compounding pharmacies could legally make and sell these. (the evidence rundown, and the argument in NYT Opinion)

Here is the part I keep sitting with. Ahead of the vote, Health Secretary Robert F. Kennedy Jr.’s office named eight new members to the committee, six of them with ties to the peptide business. And Julia Belluz made the point in her Times essay that lands hardest for me: the companies could run real trials and seek approval, and the fact that they have not reads like a quiet admission the products probably will not hold up.

Where I land, personally. As stated before, I am not there yet. A GLP-1 was my game-changer, so I understand what it feels like when something finally answers a need you could not solve any other way. If a peptide is that for someone, the thing that changes their life, I am not going to sit here and judge it, even without FDA approval. I am just personally not at the point where I would put something into my body based on this little human evidence. And that is the whole issue: how thin the evidence is.

Every one of the articulations below comes from the FDA's own scientific review, the documents its staff posted before the vote, reported by the New York Times and confirmed in STAT, TIME, and NPR. I checked them against multiple sources to be sure I was being fair.

• TB-500 was originally a veterinary drug for making racehorses and racing greyhounds run faster. The reviewers found one mouse study saying it healed wounds, one cell study saying it did nothing, and zero studies in humans. I am not a greyhound, so I will pass.

• For KPV, the FDA could not find any published data on whether it is safe or works in real patients. The one human-adjacent test was run on cadaver skin, where it barely absorbed. When your best data is a cadaver, I have questions.

• MOTS-c is being considered for obesity and osteoporosis on the strength of some animal and cell studies, no published human research, and almost no safety data. Weighed for obesity with not one human trial. Cool, cool.

• Epitalon is extracted from the pineal glands of cattle and sold as an anti-aging, live-forever compound, on the strength of a few mouse studies and one in monkeys. The FDA’s own note added that long-term use could, in theory, promote cancer. Cow-gland extract, might grow tumors, marketed as longevity. I guess some monkeys are close enough to humans?

In fairness, the other side. Of the six, BPC-157 has the most human evidence, and it is still tiny: a Phase 2 ulcerative colitis trial in Croatia reportedly showed real benefit, but the full data was never published for anyone to check, and a registered safety trial was quietly abandoned. Fewer than about 40 humans have ever been studied, with no placebo-controlled trials. The most honest defense is not that these clearly work. It is that nobody runs the big trials because these peptides cannot be patented, so there is no money in proving them. That is a real point. It also does not change what a person weighing an injection today has to go on, which is almost nothing.

A gut-check across the border. On food and chemicals, let’s be honest, the US is rarely the strict one. Europe pulled dyes and additives we still allow years before we did. So it is worth asking how the countries we usually trail are handling peptides. The answer: they are holding the line. The EU has not approved any of these, no European doctor can prescribe them, and there is no move there to open a compounding pathway. Australia went further and banned BPC-157 and TB-500 for human use outright. Japan and Singapore prohibit most unapproved peptides. The places looser than us are Russia, where one of these is sold as a nasal spray, and countries like Thailand and Mexico with thin oversight, plus China, which makes the world’s gray-market supply.

If you want the calm, evidence-first version in audio, NPR’s Short Wave did a good one this week, “Does the science of peptides live up to the hype?” (listen)

🌾 Is fibermaxxing a thing, or just this year’s protein?

If 2025 was the year of protein, 2026 is definitely the year of fiber. “Fibermaxxing” went viral on TikTok, the McDonald’s and PepsiCo CEOs both named fiber the top food trend of the year, and SunChips Fiber and Smartfood Fiber Pop are hitting shelves. The trade press saw it coming back in 2024, when one headline called it fiber’s moment in the Ozempic age. So the question is fair: is this real, or is fiber just the next nutrient we are all about to over-track?

Here is the honest answer, and it starts with a question I could not stop chewing on. We keep hearing we should hit 25 to 38 grams of fiber a day. But be honest with me, has anyone ever hit that?

For modern, industrialized humans, basically no. Americans average around 15 to 17 grams a day, roughly half the target, and that number has barely moved in decades. Only about 5 percent clear the bar. So we have been quietly failing this goal for as long as anyone has measured it. Fibermaxxing did not discover a new problem. It slapped a fun name on a very old one.

But someone did hit those numbers, and that is where the target comes from. It is not an invented wellness figure. It is a fraction of what humans used to eat. Paleolithic diets are estimated at 50 to 100-plus grams of fiber a day. The studied rural communities where heart disease and colon cancer were once rare ate around 100. The 25-to-38 target is a modest floor pegged to how people ate before the food supply changed.

Which is where my own hunch was wrong. I assumed people 40 years ago, eating worse in plenty of other ways, were getting less fiber than we are. Not really. The big fiber collapse was not the last few decades. It was the industrialization of food, refined flour, stripped grains, packaged everything, which mostly happened earlier and then held. Since then it has been a low, flat plateau. Your parents and grandparents in 1985 were getting about the same sad 15 grams you are. The modern junk did not lower our fiber this decade. It lowered it a century ago and never gave it back.

So how did the Blue Zones and the Mediterranean diets we all romanticize get to 100? They ate beans, every day. Beans are the cornerstone of every long-life diet on earth, black beans in Costa Rica, lentils and chickpeas around the Mediterranean, soy in Okinawa, and people there eat roughly four times as many as we do. Add minimally processed whole grains like barley and steel-cut oats, tubers like the Okinawan sweet potato, and piles of greens, and you land at 50 to 100 grams without thinking about it. Fiber was never the goal. It was the byproduct of eating almost entirely whole plants. We have to reverse-engineer 30 grams with chia puddings precisely because our default food quietly deleted it.

Then why the obsession now, if our intake has not budged? Three things converged. GLP-1s made everyone curious about the hormone their own gut makes, and fiber is the natural lever for it: your gut bacteria ferment fiber into short-chain fatty acids, which nudge your intestinal cells to release your own GLP-1. That is real, and it is also a whisper next to the drug’s shout, so no, fiber is not nature’s Ozempic. Second, gut-health science rebranded fiber from boring roughage into food for your microbiome. And third, the wellness pendulum swung off protein and needed somewhere to land.

So, is fibermaxxing a thing? The gap is real and old, the target is legit, and paying attention is long overdue. But “maxxing” to 40 or 50 grams overnight mostly buys you a rough afternoon. The move is not extreme, it is boring and ancient: hit the normal number from real food, lean on beans and oats and greens, and if you are on a GLP-1, it matters even more, for staying full and staying regular. The longest-lived people on earth were fibermaxxing before it had a hashtag. They just called it dinner.

Until next week,

Helaine

P.S. If one line in here was useful, forward it to the person who needs it!

Important reminder: I am not a doctor. This is one person’s reporting and experience, not medical advice. Talk to yours before you change anything.

Who am I? Helaine Knapp is the founder of CityRow, a fitness company she built and scaled for a decade before selling in 2024. She is also the author of Making Waves, host of the Step Into Next podcast, and an executive advisor and coach working with founders and leadership teams navigating growth and transition. She has been on her own GLP-1 journey for nearly two years and is building something for everyone navigating this one.

helaineknapp.com · Substack

Making sense of the chaos, together.

Hi friends,

Happy Tuesday and welcome back to cutting through the chaos, together.

What’s inside: The Medicare moment and what I told my grandma when she asked if she should consider a GLP-1. Plus what you actually need to know about mixing GLP-1s and cannabis.

📊 A risky experiment with older bodies

The conversation shifted this week. Scientific American framed what’s happening right now as an experiment, and not designed on purpose.

Medicare GLP-1 Bridge started July 1 at $50 a month. As mentioned many times, that’s genuine access for millions of older adults. But here’s the thing: these drugs have been in wide use for weight loss for roughly five years in younger populations. We have almost no long-term data on what happens when you’re seventy, and you take one of these drugs for five, ten, or twenty years. We’re learning that in real time, in millions of bodies at once.

That matters because the side effects that feel manageable at forty-five might hit differently at seventy-five. Nausea, constipation, fatigue, these land harder in older bodies, and they can compound other medications. Not saying don’t take them, just saying the clinical trial for aging is happening now.

The other signal is vision. Rutgers researchers found that people taking GLP-1s have a higher risk of ischemic optic neuropathy, which is a sudden blockage of blood flow to the optic nerve. The absolute risk is still low. But the finding clusters in men and women aged 50 to 65. What matters clinically: if you’re on these drugs and you suddenly see flashing lights, or a dark spot appears in your vision, that’s a “get to an eye doctor today” situation, not something to wait out.

Both conversations are pointing at the same thing: we’re expanding access to these drugs into populations and timescales we haven’t studied yet. From all that I’ve read, there are quite significant benefits, and the macro trends point in the positive direction. It’s not a reason to stop, but it is a reason to pay attention.

🚫 Myth bust (The relationship between GLP-1s and cannabis)

What actually happens when you take GLP-1s and use cannabis at the same time?

The simple version people expect: THC stimulates appetite, GLP-1s suppress it, so they cancel out?

Meh? Kinda, not really.

THC and GLP-1s do work on overlapping appetite pathways, but that doesn’t mean they neutralize each other. People who use both report that the GLP-1’s appetite suppression often still dominates. The appetite signal from cannabis doesn’t erase the fullness signal from the drug. Instead, what people report is confusion, sometimes you get the munchies, sometimes you don’t, sometimes you want to eat but can’t.

But the real complexity is timing and form. This is where the method of consumption actually changes the interaction.

If you smoke: THC hits your bloodstream through the lungs and peaks within minutes. It’s relatively fast and relatively short. The GLP-1 is still working on your stomach (slowing it down), but the appetite effect is bounded.

If you eat an edible: THC is absorbed through digestion, and because GLP-1s slow gastric emptying, that absorption is unpredictable. An edible might hit in an hour or take several hours. It lasts longer than smoked cannabis. You’re looking at a prolonged appetite stimulation on top of a drug working against it all week. Some people report the unpredictability alone is enough to avoid it.

If you use a tincture: You’re in between. Absorbed through the mouth faster than an edible, slower than smoke. Longer lasting than a joint, shorter than an edible.

There’s another conversation happening that’s separate from appetite. Some people are using cannabis specifically to manage nausea from the GLP-1 itself, which is a side effect early on for some users. They’re not chasing the munchies. They’re chasing relief.

The medical piece worth flagging: both GLP-1s and heavy cannabis use slow gastric emptying. Used together, especially with edibles or tinctures, you’re stacking two mechanisms that delay your stomach’s ability to move food forward. This raises the risk of gastroparesis, a condition where the stomach stops emptying food properly, causing severe nausea, vomiting, abdominal pain, and malnutrition.

For most occasional cannabis users on a GLP-1, this isn’t the main concern. The real risk is for heavy, chronic users. After years of daily cannabis use, some people develop Cannabinoid Hyperemesis Syndrome (CHS), a distinct condition characterized by cyclical episodes of severe vomiting and abdominal pain (with the oddly specific symptom of relief from hot showers). CHS is well-documented in the medical literature. If you’re on a GLP-1 and using cannabis daily, especially edibles, you’re essentially doubling down on gastric-emptying delay. This isn’t theoretical. It’s a conversation worth having with your prescriber before it becomes a problem, particularly if you’re a heavy user.

The honest part: none of this is studied in people actually taking GLP-1s. There’s one small randomized trial showing cannabis lowered circulating GLP-1 concentrations in the blood and raised ghrelin (the hunger hormone), with oral cannabis showing a bigger effect than smoked or vaporized. But that’s not the same as what happens in a person on a GLP-1 medication using cannabis at home.

What exists is what people are reporting: conversations on forums, experiences shared one to one. And those conversations are saying: it’s complicated, form matters, and your mileage varies wildly depending on how often you use it and why.

💬 What I’m thinking about

The aging question sits with me. My 90 year old grandma was getting curious about it. I’m gave her a hard no, but she can talk to her doctor… and I appreciated her interest in what I’m writing about. All joking aside, when slightly older people ask if they should consider one, I pause. Older bodies require more data and we’re moving this drug faster than most data can keep up.

Until next week,

Helaine

P.S. Forward this to someone who asked you about cannabis and their GLP-1 and you didn’t know what to say.

I am not a doctor. This is reporting and experience, not medical advice. Talk to yours before you change anything.

Hi friends,

Happy Tuesday and welcome back to your weekly breakdown of all things GLP-1’s and how to cut through the chaos.

What’s inside: a quiet-but-real news week, my two cents on the essay everyone is arguing about, and the thing I find most interesting about these drugs and sugar, which starts with the fact that they were built for something else entirely.

📊 The news, fast

• GLP-1 use hit a new high. One in nine U.S. adults now takes a GLP-1 for weight loss, up from one in 12 a year ago and one in 33 in 2024, according to new Gallup data out this week. Over the same stretch, the national obesity rate slipped from its 2022 peak of 39.9% to 36.4%. The curve is steep, and it is still climbing. (Gallup)

• The generics countdown started. The FDA accepted Sandoz’s applications for a generic tirzepatide autoinjector covering all of Mounjaro’s uses. It is the first real step toward a cheaper version of one of the two big drugs (though realistically, Lilly’s U.S. patents run to 2036, so barring a court challenge or settlement, do not expect a generic on shelves before the mid-2030s). (Fierce Pharma)

• Meanwhile, the coverage whiplash continues. A Boston Globe piece this week laid out how commercial and state plans are pulling back: Blue Cross Blue Shield of Massachusetts and Point32Health dropped weight-loss coverage in January, the state commission covering roughly half a million public employees dropped it July 1, and Medicaid there ended weight-loss-only coverage this month, all while the cost-effectiveness data says the drugs are worth it. So even as Medicare opens a door and CVS reopens one, a lot of under-65 plans are quietly closing them. (Boston Globe)

💬 A word on the essay everyone is arguing about

The New York Times ran a first-person essay this week by Caroline Calloway about taking Ozempic, and it is doing what it was built to do: getting a reaction. It is provocative, it is pretty polarizing, and I get why. (the essay)

Here is what I keep coming back to. For a long time this conversation has had two very different ends: silence on one side, spectacle on the other, with a lot of talk about overuse mixed in. This essay lives at the spectacle end. What almost never gets airtime is the middle, where most people really are, and the reason is simple: spectacle is what gets clicks and views and gets rewarded, and the quiet middle does not.

A while back I wrote about the woman who spoke to CNBC about being on Wegovy and would not give her last name. Set her next to an essay this loud, and you can see the whole spectrum at once: silence to spectacle, with an enormous, voiceless middle in between.

Most people are somewhere in the middle. Curious. Watching how it fits into their life, or noticing that it already has. Not sure yet whether they want to say so out loud, because for all the noise, this is still a quietly taboo thing for a lot of people, and the loudest voices in the conversation are the least representative of it.

That is the part worth holding onto. If you are in the quiet middle, intrigued and unsure and not ready to announce anything, that is not a failure to have a hot take. That is where most of us are. (For the longer version of how stigma shapes all of this, my earlier piece is here.)

🍬 Do GLP-1s change the way you crave sugar?

Start here, because it reframes everything: these were diabetes drugs first. GLP-1s were built to manage blood sugar, and the appetite and weight effects were the surprise that showed up after. (Stanford Medicine) So the relationship between these drugs and sugar is not a side plot. It is the origin story.

Which is why the myth I want to bust is a good one: that these drugs “change your taste buds.” Sort of, but not where you think. In a study of more than 400 people on semaglutide or tirzepatide, about one in five said food tasted sweeter or saltier than before, so taste perception really can shift for some. (Diabetes, Obesity and Metabolism, via Healio) But that is the smaller part of the story. The bigger, better-documented effect is in the brain, not on the tongue. A peer-reviewed trial found tirzepatide significantly cut people’s preference for foods high in fat and in simple sugar, and deep-brain recordings in one patient showed it quieting the nucleus accumbens, the brain’s reward hub, though that effect faded over months. (tirzepatide trial, deep-brain recordings) Semaglutide points the same direction in its own research. (review) So the honest version is this: they change what you crave more than what you taste.

Here is the wrinkle I did not expect, and it matches my own experience exactly. These drugs do not make you want more sugar. What they do is make sugar the last craving standing. They quiet the pull toward fatty, savory, heavy food first and hardest, so when almost everything else goes quiet, the small wish for something sweet is what is left. I have never been a candy-over-cookies person, but lately a couple of Swedish Fish sound weirdly appealing on a day when most other cravings barely register. It is the last guest at the party.

The science backs up the feeling. Reviews note that while semaglutide cuts intake of high-fat, energy-dense food, animal studies suggest it may not reduce, and might even nudge up, consumption of low-to-moderate sweetness. (review) And in that same taste study, the people who found sweetness more intense also reported more fullness and less appetite, which means a couple of bites of something sweet can register more strongly and satisfy faster than a whole serving used to. (Diabetes, Obesity and Metabolism, via Healio) So it is not more sugar. It is less of everything else, a sharper hit from a little, and a few bites here and there instead of the whole bowl.

Turns out I am not alone, and the food industry noticed. Better-for-you candy is having a real moment, with low-sugar, higher-fiber takes on the classics showing up everywhere, Swedish-fish styles included. The little treat is not going away. It is just getting reformulated.

One thing to hold onto: like most of what these drugs do, the craving-quieting can fade over time, which is part of why the habits you build while the noise is down end up mattering as much as the drug itself.

Until next week,

Helaine

P.S. If one line in here was useful, forward it to the person who would find this interesting!

Important reminder: I am not a doctor. This is one person’s reporting and experience, not medical advice. Talk to yours before you change anything.

Who am I? Helaine Knapp is the founder of CityRow, a fitness company she built and scaled for a decade before selling in 2024. She is also the author of Making Waves, host of the Step Into Next podcast, and an executive advisor and coach working with founders and leadership teams navigating growth and transition. She has been on her own GLP-1 journey for nearly two years and is building something for everyone navigating this one.

helaineknapp.com · Substack

Making sense of the chaos, together.

Hi friends,

Happy Tuesday and welcome back to breaking down all the things.

Quick note: this is my first week moving the newsletter fully onto Substack. Thank you for rolling across platforms with me, and for being on this early part of the journey!

What’s inside: three coverage moves from the past week that quietly change who can get these drugs, the peptide craze that everyone suddenly wants to talk about (me included), and the truth behind “Ozempic babies.”

📊 The news, fast

• CVS reversed itself on Zepbound. Effective October 1, CVS Caremark is putting Zepbound back on its commercial formularies as a preferred option and adding Foundayo. If you were one of the roughly 200,000 people pushed off Zepbound and onto Wegovy last summer, it is on its way back. (Managed Healthcare Executive)

• The Medicare GLP-1 Bridge went live July 1. The big moment is finally here! Eligible Part D members can now get Wegovy or Zepbound for $50 a month. BUT, the catches are the real story: you have to clear BMI rules and prior authorization, there is no formal appeals process, and that $50 does not count toward your deductible or your $2,100 out-of-pocket cap. It runs through 2027, and what happens after depends on a program that keeps getting delayed. (the details, via AARP and KFF)

• The compounding decision did not land. The window everyone expected to close and that I mentioned last week got pushed to July 30. So the cheapest route millions of people rely on is still in limbo, not gone. (FDA notice )

💉 Let’s talk about peptides

Every week it feels like there is more talk about peptides, and while GLP-1’s are a peptide, most questions / edge conversations are on the whole batch of others. So let me be upfront about where I stand.

I am not taking them. I have dug into them, and after digging in, I am still not taking them. But I am paying close attention, because this is clearly becoming its own craze, and it lives right next door to everything we cover here. (Worth saying out loud: GLP-1s are peptides too. The difference is that they went through the trials. Most of these have not.)

The short version of the craze: once people got comfortable injecting one thing, the ceiling came off. BPC-157 (a lab-made peptide based on a protein fragment found in the stomach), TB-500, and a long list of others are being sold online and injected at home, marketed to heal your tendons, calm your gut, sharpen your brain, slow aging, all of it. The claims are enormous. The human studies are close to nonexistent.

That is not me being dismissive. It is the state of the evidence. A few places worth your time if you want to see for yourself:

• Eric Topol’s The Peptide Craze is the clearest single overview of what we do and do not know. It is from July 2025, so it is a little dated, but I went looking, and nothing major has changed on the science since.

• STAT and Undark ran a careful investigation into BPC-157, the most hyped one of the bunch, and found that almost all the data traces back to animal studies from a single research group. (STAT, Undark)

• A 2026 peer-reviewed review put it plainly: after more than thirty years of research, there is still no approved formulation, no validated dose, and no completed phase II trial.

Why I am raising this now: the FDA holds a public meeting on July 23 and 24 to weigh whether several of these peptides, BPC-157 among them, should be allowed back into compounding. That is the moment the gray market has been waiting for. A “yes” would not mean “FDA approved,” but it would change the whole conversation, and I will be watching it closely.

Where I personally land, for whatever it is worth: I am fascinated by a few of these, and I am wide open to changing my mind the moment real studies show up. What I will not personally do right now is inject something that is not FDA approved. And some of them I am simply cautious about. Particularly anything in the growth-promoting family gives me pause, because growth is not selective. It grows the good stuff and the bad stuff, and researchers flag that same worry in the literature. That is not a small thing to wave away.

I may go deep on this one on Substack soon, because the volume of questions tells me it is time. If there is a specific peptide question you want answered, hit reply and tell me.

🚫 The myth I want to bust: “Ozempic is a fertility drug”

You have seen the “Ozempic babies” headlines. Here is the precise version, in three parts.

One: it does not make you fertile. That is the headline, and it is wrong. Nothing about these drugs acts on your reproductive system. They are not a fertility treatment, full stop.

Two: it causes weight loss, and weight loss can restart ovulation. This is the real mechanism, and it is why the surprise pregnancies are real. For women whose cycles had stalled, especially with PCOS, dropping a meaningful amount of weight can bring ovulation back and settle the hormones that were out of balance. Doctors have watched the same thing happen for years after major weight loss from surgery. So the pregnancies trace to the weight loss, not to the drug doing anything fertility related. (National Geographic)

Three: your oral birth control may be less reliable, and here is why. These drugs slow down how fast your stomach empties, which can mean you absorb less of a pill you swallow. That is a concern for oral contraceptives specifically, so anything non-oral (an IUD, an implant, the patch, the ring) sidesteps it. Worth knowing which drug matters most here: tirzepatide (Zepbound, Mounjaro) carries a label warning to use a backup method for four weeks after you start and after each dose increase, while semaglutide (Ozempic, Wegovy) does not. (the difference, explained)

None of this makes it a fertility drug. It is weight loss doing what weight loss does, plus an absorption quirk worth knowing about. The “Ozempic baby” headline exists because it gets the click, not because the science says the drug makes you fertile. One thing that is true across the board, though: these drugs are not considered safe in pregnancy, so the guidance is to stop well before trying to conceive.

If you are on one of these and taking the pill, that is the sentence to forward to a friend.

💭 The reframe I keep thinking about

For most, the strangest part of the experience on a GLP-1 is not the dropping number on the scale. It is the quiet. After nearly two years on this, the thing I still notice most is that the constant negotiation with food simply stopped. So many of us describe the exact same relief. My friend Derek Flanzraich wrote a piece this week that put words to the macro meaning of that quiet better than anything I have read, and I want to share it with you and why it landed so well for me.

The frame Derek lands, and the one I loved: these are not really weight-loss drugs, they are identity drugs.

The piece clicked for me through the connection to the work by James Clear. I have read his Atomic Habits at least four times, and his whole idea is that every small action is a vote for the person you are becoming. What Derek adds is where the food noise fits in. He describes it not as weak willpower but as a running argument between what you say you want and what you keep doing. If you are someone who wants to skip dessert but never quite does, your brain notices the gap and quietly writes a story: you are someone who cannot follow through. What the drug does, in his telling, is turn that argument down enough that skipping dessert stops being a battle. Skip it once and it is nothing. Skip it enough times, without white-knuckling it, and you quietly become someone who skips dessert. The drug did not cast the vote. It cleared enough room that you could. As Derek puts it, the medication is the catalyst, not the system, and the habits are the part that lasts.

This is why I keep coming back to his piece. The relief people describe on these drugs is real, and it usually gets waved off as “the appetite thing.” Derek makes the better case, that the quiet is what finally creates space to build habits that stick. And that reframes coming off them too: build the habits while the noise is down, and you may not need the drug forever. Derek’s piece is here, and his newsletter, 5HT, is worth your inbox.

Until next week,

Helaine

P.S. If one line in here was useful, forward it to the person who needs it!

Important reminder: I am not a doctor. This is one person’s reporting and experience, not medical advice. Talk to yours before you change anything.

Who am I? Helaine Knapp is the founder of CityRow, a fitness company she built and scaled for a decade before selling in 2024. She is also the author of Making Waves, host of the Step Into Next podcast, and an executive advisor and coach working with founders and leadership teams navigating growth and transition. She has been on her own GLP-1 journey for nearly two years and is building something for everyone navigating this one.

helaineknapp.com · Substack

Making sense of the chaos, together.

I write about this space wearing two hats. As a consumer, what I want first is simple: to cut through the clutter, to make sense of the wall of marketing and counter-marketing being thrown at all of us about these drugs. Then, as a builder, I want something else, to step back and synthesize, to take the scattered pieces of this thing and ask what they add up to: what it does to the industry, and what the future looks like, midterm and long. Being at the front of a changing tide rather than pulled under it comes down to reading the macro early and reading it right.

Plenty of people are mapping the secondary and tertiary effects of GLP-1s, and I think the lens is generally fine, but also too general. As mine sharpens, what comes into focus is not the drugs, it is the people and how they connect with the tool, and from there the infrastructure, the support, and the whole shape of the category follow. So this piece steps back to ask the question underneath the noise: what does consumption, and our relationship with these drugs, actually look like in the future world where we’ve solved both affordability and accessibility?

The trade that got faked out

In 2023, the smart money shorted snacks.

The logic looked clean. A drug had arrived that turns off hunger, the people taking it were buying less food, and if you ran that forward, the packaged-food giants were facing structural decline. The stocks sold off on it. Headlines wrote the obituary for the potato chip.

The mechanism was real. The most careful study we have, out of Cornell, found that within six months of starting a GLP-1 a household cuts grocery spending by about 5 percent, more than 8 percent in higher-income homes, with fast food and coffee down around 8 percent. The cuts land hardest exactly where you would expect, on the ultra-processed, calorie-dense, craving-driven food.

So why did the trade get faked out? Because of one detail the short missed. The spending cut holds for the people who stay on the drug. It reverses for the people who quit. In the Cornell data, roughly a third of users stopped during the study window, and their food spending climbed right back to where it started. The recovery everyone pointed to as proof the bears were wrong was not the drug failing to change behavior. It was a third of the users walking away from the drug.

That is the whole game hiding in a footnote. The snack short was never wrong about appetite. It was wrong, or early, about adherence. Its entire profit and loss rides on a single question: when these drugs are cheap and everywhere, do people stay on them?

Here is the part I keep coming back to. If everyone stays on, the snack short is eventually right, and the demand destruction is permanent. If everyone cycles on and off, the short is wrong, and what food companies face is not a decline but a choppy, fluctuating demand pattern they have to learn to ride. The trade is not a bet on the drug. It is a bet on human behavior. And human behavior here does not have one answer. It has five.

The wave is already here

This did not creep up on us. It went mainstream earlier this year the way things do now, through people we recognize, when public figures led by Serena Williams started talking openly about being on a GLP-1. Fronting a Super Bowl campaign for the telehealth company Ro, Williams framed it as biology over willpower, science over vanity, and that did more to normalize these drugs than any clinical trial could.

But culture is not a market. Supply and price are. The first oral GLP-1 for weight loss, the Wegovy pill, launched on January 5 and became one of the strongest drug launches in US history by volume: three million prescriptions in just over five months, more than 80 percent of them to people who had never been on a GLP-1 before. It is not stealing patients from the injection, it is pulling in millions who were never in the room. Eli Lilly’s Foundayo followed in the spring, a non-peptide small molecule cheap enough to manufacture at scale, which is what makes durable mass pricing real. Copays are already reaching twenty-five dollars, the pipeline behind them runs deep, and a drug that was a niche is on its way to a third of the country. Which makes now the right time to think beyond pipeline and cost, to a future state (likely not that far out), when everyone has easy, cheap access. Then, the interesting question is not whether it works, but who all these people are, and what their relationship with the drug becomes.

Not one future. One question.

I see two lazy takes about where this goes.

The first is that cheap and oral turns GLP-1s into a casual lifestyle product. On for a wedding, off for the summer, treated like a juice cleanse with a prescription.

The second is the opposite, that it turns everyone into a statin patient, quietly medicated for life, the way an earlier generation absorbed cholesterol pills into the daily routine and stopped thinking about it.

Both are real outcomes. Neither is the outcome, because they describe different people. And the thing that sorts those people is not willpower, and it is not even how their body handles the drug. It is a simpler question, the one I think the whole market is about to organize itself around: what is this drug to you? What job does it do in your life? Because that role, far more than your dose, or how long you have been on, or how loudly you talk about it, is what predicts how you behave and what you will buy.

One thing does sit upstream of the question, and it is worth acknowledging: whether your body can take the drug at all. Some people cannot. The side effects end it before any of the rest applies, and they become a type of their own. It also creates a selection effect nobody prices in: the people you see using these drugs gracefully are disproportionately the ones who tolerate them well. Everyone who got hammered washed out before the story started.

Everything else, the dose, the secrecy, whether you are on right now or between rounds, is a layer, not a type. A person can run loud or quiet, full dose or a sliver, and still be the exact same kind of customer. So answer the one question, what is the drug to you, and you do not get a future. You get five personas that will crave different infrastructure to support their new relationship with a drug that affects multiple areas of their life.

The five personas

Picture the next decade as a room with five people in it. They can be on the identical molecule and be completely different customers, because each one has hired the drug to do a different job.

The Lifeline. To this person the drug is medicine. They came to it through a doctor, for something that genuinely matters to their long-term health: diabetes, a heart or metabolic risk, weight that had crossed from cosmetic into clinical. It is treatment, not a tweak. For the Lifeline this is simply a medicine they will take for the long haul, the way a person takes a blood-pressure pill, because their health is measurably better with it than without it.

The Staple. To this person the drug is a staple. Maybe they started for a proactive-medical reason or to lose weight, felt the benefits ripple out beyond the scale, and now it is just part of how they live, folded in like a daily vitamin. Whether they take a full dose or a sliver, whether they announce it at dinner or never bring it up, does not change what they are: someone who tried it, liked the life it gave them, and is not giving that up. It is mostly elective, so today they pay out of pocket or work to get it covered, and they will keep finding a way, because to them this is not treatment, it is just better living.

The Cycler. To this person the drug is a tool. They are not treating a condition, they are reaching for a goal. They use it in deliberate stretches, hit the target, step off, and pick it back up when they decide to. They are the one holding the on-off switch. The open question hanging over the Cycler, the one the science still has not answered, is whether deliberate on-and-off use holds the result over years. They are running that experiment in real time.

The Longevity Optimizer. To this person the drug is an upgrade. Not heavy, not sick, they run a GLP-1 for what sits underneath: the metabolic markers, the inflammation, the long bet on healthspan. One input in a stack they are forever tuning. They are the newest face in the room and the least studied in this particular use, which is worth a note rather than an alarm. For the Optimizer this was never about sickness, or even weight. It is engineering wellness.

The Locked Out. To this person the drug is a closed door, and it is not their fault. For some, the body refused it and the side effects made it unlivable. For others, the door was money, the coverage that lapsed or the price that spiked, and they came off a cliff they never chose to jump from. Either way the benefits are real and sitting right there, just out of reach. This is the most sympathetic person in the set, and the one the next few years are built to rescue: as the pill gets cheap and reliable and the gentler molecules arrive, the door that was shut starts to open. The Locked Out is not a failure. They are a waiting list the future will hopefully clear.

The caveat

A reminder: I am by no means a doctor. Everything above is speculation and hypothesis, built from how I see this space and from listening, closely, to a lot of people living it. And for the record, I am card-carrying Staple community myself, so read all of this as one person’s view, not a verdict.

When I say tens of millions may stay on these for life, that is me hypothesizing a path, not calling a certainty, and it is a path none of us has watched all the way down. Statins earned their permanent spot in the daily pillbox over more than thirty years of evidence; lifelong GLP-1 use, in young and basically healthy people mostly chasing a number, is about three years old. The ancillary benefits piling up in the research, the heart, the kidneys, maybe more, look real and encouraging. But no problems so far is not a track record when the so-far is this short. Call my posture toward the statinification story conviction with an asterisk, and the asterisk reads: pure hypothesis.

Why the personas are the whole point

Most GLP-1 commentary is chasing a number: how big, how fast, how much demand destroyed, how much value created. The thing that matters is not the number. It is a set of relationships, the ones people form with this miracle of a drug, and what it becomes to each of them. That is what decides how they behave, what they buy, and how much of their wallet flows into the drug and the entire economy of products and tools growing up around it.

Which is why, if you are trying to build rather than narrate, the segmentation is the asset. Each of these five is asking for something different, and almost none of it exists yet.

The Lifeline needs what any chronic patient needs: reliable, covered, forever supply, and the clinical infrastructure around a medicine you take for life. The Staple needs it to stay easy, affordable, and socially normal, the price and the permission to keep a good thing going, plus a real path to getting it covered. The Cycler needs the thing the trials never built, a protocol for coming off and holding the result: the maintenance dosing, the microdosing, the support that turns “I stopped” into something other than “I regained.” The Longevity Optimizer needs the data and the framing to run this as healthspan infrastructure rather than a weight drug. The Locked Out needs the next molecule, the gentler tolerability, and the cheap, steady access that finally opens the door.

That is five distinct products, five distinct journeys, sitting underneath a category everyone is still describing with a singularity. I am not certain which of these cohorts ends up largest, or whether the lines hold exactly where I have drawn them. Nobody can be, because the cheap-pill population only started arriving a few months ago. But I am confident the useful work is here: not predicting whether GLP-1s are good or bad for snack stocks, but reading what the drug becomes to real people, earlier and more precisely than anyone else, and building for whichever version of them you choose to serve. Get the people right and the behavior, the preferences, and the wallet all follow. Get them wrong and you are shorting snacks in 2023, technically correct about the mechanism and still on the wrong side of the trade, because you bet on one behavior when there were always five.

Affordable enough to never really stop is the gravitational pull of this whole story. But not everyone falls into the same orbit, and the work is in knowing exactly who falls where

This is my hypothesis. I would love to hear yours.

Honest truth about me: I have been borderline obsessed with my hair for most of my life. That does not mean we have not been through it together, from too frizzy to too curly to too straight to too thick. I have rearranged my actual life around my hair. I have gone to genuinely unreasonable lengths to protect a blowout, and no, I will not be telling you how long I have made a single blowout last, but it’s impressive, thank you. My mental state has probably always been quietly tied to how good my hair looks. A bad hair day can set the tone for everything that comes after it. If you are a woman, there is a decent chance you just nodded, because most of us have a long, complicated, deeply personal relationship with our hair. I am no exception, and I am not going to pretend to be.

So when I tell you that the hair thinning was, by a landslide, my worst side effect on a GLP-1, I need you to hear it the way I mean it. Not as a footnote. Not as vanity. As the thing that scared me most.

And here is what gets me, looking back. I was braced for nausea. I was braced for every kind of stomach issue. I was hyper-prepared to protect against muscle loss. Never once did I think my hair would be brought into this. I did not notice it was happening to me for the first couple of months. Then one day I felt my ponytail and thought, that feels thinner. It was one of the most frightening moments. I dug in. I talked to friends, to my hairdresser, and I remember saying to someone, am I trading losing weight for my hair? For a little while, I think the honest answer was yes, and it was terrifying. But also, would I trade that? Yikes.

When you go looking online, there is a lot, and it splits into two unhelpful camps. One says do not worry, it always grows back. The other sells you a thirty-dollar monthly bottle of panic, or a medication that promises to grow hair back everywhere, which is its own kind of terrifying. The truth lands somewhere neither camp will tell you, because it is genuinely different for different people.

Here is where we are going to break it all down:

• What is actually happening to those hair follicles

• The timeline for the shedding

• Why it is different for women, and the honest “does it come back” answer

• What actually works, sorted by what the evidence says

• What I did, and where I have landed

What is actually happening

The reassuring part first, because it is real and it is the most likely story for most of us who started a GLP-1 and then had hair thinning.

When you lose weight quickly, your body reads it as a shock. Not a bad-intentions shock, just a big, fast change, the same way it reads a high fever, a major surgery, or childbirth. In response, a chunk of your hair follicles that were happily growing get pushed early into their resting phase, all at roughly the same time. A couple of months later, that whole cohort sheds at once. The clinical name is telogen effluvium, and yes, this is the thing nearly everyone is actually talking about when they talk about GLP-1 hair loss. It is the leading explanation in the research, and the single most important thing to know about it is that it is usually temporary. The follicle is not dead. It is resting. When the shock passes and your body feels safe and well-fed again, those follicles wake back up.

I covered the basics of this in a newsletter a few weeks back, so I am going to keep the 101 short here and spend our time on the parts I did not get to: the timeline, the women-specific story, and the honest sort of what to actually do.

One phrase you will run into is worth decoding, because it is quietly reassuring once you understand it. The research calls this nonscarring hair loss. Nonscarring means the follicle itself is not destroyed and no scar tissue replaces it. It is intact, just resting, which is exactly why it can grow back. The other category, scarring hair loss, is when inflammation permanently destroys the follicle, and that loss does not return. The GLP-1 kind is the nonscarring kind. Your follicles are still there.

So is the drug doing something sinister to your follicles? The data mostly says no, and this genuinely reassured me. In a real-world cohort of more than 400,000 people, starting semaglutide or tirzepatide was linked to a higher rate of nonscarring hair loss, and the signal was strongest in the people losing the most weight the fastest, at the higher doses. Two details I found steadying. First, the comparison group in that study was people starting metformin, an older, non-GLP-1 diabetes drug, and the autoimmune type of hair loss actually showed up more often in that metformin group than in the GLP-1 group, which is a strong hint these drugs are not switching on an immune attack against your hair. Second, the signal was specific to semaglutide and tirzepatide. The older GLP-1s, liraglutide, dulaglutide, exenatide, and lixisenatide, did not show it. That pattern, strongest with the fastest loss and absent in the gentler older drugs, is exactly what you would expect if this were a shedding response to rapid loss rather than the drug poisoning your scalp.

TLDR: it is mostly the speed of the loss and the deficit, meaning not enough total fuel, not enough protein, and not enough of the micronutrients that hair depends on, iron above all, then vitamin D, B12, and zinc. It is not the drug being toxic to your follicles. And that distinction matters enormously, because speed and deficit are things you can actually do something about.

The timeline, which is the part that fools everyone

This is the part I wish someone had drawn for me on day one, because the timing is genuinely deceptive and I would have avoided a panic had I expected this series of events.

The shedding does not start when the shock to the follicle happens. With a single, clean trigger like a surgery or a birth, it starts about two to three months later. That lag is the cruelest part, because by the time hair is coming out in the shower, the cause can be months behind you, so you do not connect the dots.

But a GLP-1 is not a single event. It is months of ongoing loss and an ongoing deficit, which means the shedding can ramp up slowly and drag out over a much longer window than the textbook version. For me, the worst stretch of the shedding hit somewhere in the six-to-twelve-month range after I started, which in hindsight makes complete sense, because the trigger was not one moment. It was the cumulative months of losing.

Then, once the underlying cause is actually addressed, meaning you are eating enough and your body stops reading itself as starving, regrowth begins. The first sign is usually fine little baby hairs along the part and temples, often a few months after you correct things. Fuller texture comes later. Real, you-can-see-it-in-the-mirror recovery usually takes somewhere in the range of six to twelve months, and sometimes longer, because hair grows slowly and there is no rushing it. I am two years in now, and it feels meaningfully better than it did a year ago. The point is that the curve is real, and it is long, and the worst moment is not the end of the story. It just feels like it when you are standing in it.

Why it is different for women, and the honest “does it come back” answer

There are two different things that can be happening when a woman’s hair thins, and they look almost identical at the start. Telling them apart is the whole game.

The first is the telogen effluvium we just talked about. Sudden, diffuse, often coming out in alarming handfuls, clearly tied to a trigger like rapid weight loss, and made of normal, full-thickness hairs. The follicles are fine. This is the one that grows back.

The second is female-pattern hair loss, the genetic and hormonal kind, and it is far more common than most women realize: around 40 percent of women show signs of it by age 50, and the share keeps climbing with age. It does not come out in dramatic handfuls. It creeps. The hairs themselves get progressively finer and shorter over months and years, your part slowly widens, and there is often a family history. The tell dermatologists look for is variation in hair thickness across your scalp, some strands thick and some wispy, which is the signature of follicles shrinking. This one does not resolve on its own. It is manageable, but it needs actual treatment, and the longer it goes unaddressed, the more ground you lose.

Here is the honest, uncomfortable overlap, and it is specifically a women’s problem. A big shedding event from rapid weight loss can unmask female-pattern thinning that was already quietly underway. The shed clears out a layer of hair and reveals the slow miniaturization happening underneath, and this happens most often around perimenopause, when estrogen drops and your follicles get more sensitive to androgens. So you can have both at once. The shedding part comes back. The pattern part does not, not without help. That, right there, is the real answer to “does it grow back.” For some women it is pure telogen effluvium and it fully returns. For others, the GLP-1 shed pulled back the curtain on something that was going to need a longer conversation regardless. It is awful, and it is also better to know.

If you have ever heard a friend describe the wild shed a few months after having a baby, you already know telogen effluvium. Same mechanism. And the same unmasking can happen there too, which is why some women never feel like their hair fully came back after kids. It was two things wearing one costume.

So here is the rule I would give my closest friend. If your shedding clearly followed your rapid loss, came in diffuse handfuls of normal hair, and is easing as you stabilize and eat enough, that is the reversible kind, and your job is mostly patience and nutrition. But if the thinning keeps progressing past roughly six months, if your part is visibly widening, or if you are seeing that fine-and-thick mix, it’s not a bad idea to go see a dermatologist and get some experts working for us and our hair!

And quickly, because this is women-first but not women-only: men on these drugs shed too, and the same logic applies. The diffuse shed usually recovers. A receding hairline or crown thinning is the pattern kind and wants real treatment. If your person is on this ride alongside you, the playbook is the same.

What actually works, sorted by what the evidence says

The foundation, which is genuinely the lever. For weight-loss telogen effluvium, the actual fix is removing the shock, and ideally avoiding as much of it as you can in the first place. That means eating enough, getting a real spread of nutrients and not just hitting your protein number, and where you can, not losing faster than your body can handle. This is not glamorous, and nobody can sell it to you in a jar, which is probably why it gets the least airtime. It is also the most effective thing on this entire list. Worth knowing: the big GLP-1 trials barely tracked what people were actually eating, so the nutrition side of this has been weirdly under-examined from the start. That gap is yours to close. It is also your single best opportunity to head off one of the worst side effects before it starts.

Which raises the question I really wanted to answer here: can you still get the benefit and protect yourself the whole way? Yes. This is the part I find genuinely hopeful. The prevailing view among obesity-medicine doctors is that you can lose significant weight and protect your body at the same time, by going a touch slower, prioritizing protein and a real nutrient spread, and adding resistance training. It is not hand-waving. In a 2025 study of 200 people on semaglutide or tirzepatide who paired the drug with strength training and individualized protein, participants lost about 13 percent of their body weight but only about 3 percent of their muscle over six months. The same levers that protect your muscle, enough protein and lifting, are the levers that reduce the deficit driving your hair to shed. It is one project, not three. I went deep on the protein side of this in the protein paradox piece, and hair is one more reason it matters.

Now, the honest part, because I am not going to pretend this is easy. Eating enough when the entire point of the drug is that you are not hungry, and when some days you are nauseous and the thought of food is rough, is genuinely hard. It is the definition of easier said than done. The thing that helped me was small, dense, and sometimes liquid: a protein shake when chewing felt like too much, Greek yogurt, a few bites of something real even when I did not feel like it. stretching the time between my doses out to 10 days or more, so I would get a few days where eating actually felt possible. You are not aiming for perfect. You are aiming for enough, on the days that are hard, on purpose.

Bloodwork, which is the highest-value move almost nobody makes. If you do one thing, do this. Ask for ferritin, iron studies, vitamin D, B12, and a thyroid panel. Here is the catch that makes it worth doing properly: your lab may call a ferritin of 20 or 25 “normal,” but for hair, dermatologists generally want it meaningfully higher, in the 40-to-70 range, and most women with diffuse shedding sit below 30 (mine is!). Iron deficiency is the most common nutritional driver of hair loss in women, and a smaller appetite is a fast track to running low without realizing it. On the thyroid side, a TSH drifting up can slow your hair cycle while still being called normal. The reason this is such a good use of a blood draw is that these are the causes you can actually correct, and correcting them is what lets the regrowth clock start.

Minoxidil, the one with real evidence, and the one to understand clearly. This is the first thing the internet yells at you. Topical minoxidil, the 5 percent formulation specifically, and increasingly low-dose oral minoxidil prescribed off-label, are the genuinely studied options, and they work best for the pattern kind of loss. For pure telogen effluvium from a shed, it is optional, and the foundation matters more. For female-pattern thinning, it is one of the actual tools.

But the side effects are real and should not be glossed over, which is part of why I made the choice I did. Minoxidil commonly causes an initial “dread shed” in the first weeks, where your hair sheds more before it improves, which is brutal when shedding is the exact thing scaring you. It can cause unwanted facial and body hair, more often in women. The oral version, because it circulates through your whole body, can cause fluid retention and puffiness, lightheadedness since it started life as a blood-pressure drug, and in rare cases heart-related effects, which is why it should be prescribed and monitored by a doctor. And it is a commitment: the gains reverse within a few months of stopping. None of that means do not use it. It means go in with clear eyes, ideally with a dermatologist, knowing which lane you are in.

Supplements. The principle is test first, supplement second. A multivitamin as general insurance while your intake is low is reasonable, and it is part of what I do. But the heavily marketed hair-growth pills are mostly selling hope, which I broke down in detail when I went through Nutrafol, so I will not relitigate the whole bottle here. The short version: supplements fix deficiencies, and they do very little if you do not have one. Two cautions worth repeating. Biotin has almost no evidence in people who are not actually deficient, which is rare, and high-dose biotin can throw off lab results, including thyroid tests, which is darkly ironic given thyroid is one of the things you are trying to check. And more is not better. Overdoing selenium, vitamin A, or zinc can itself cause hair loss.

Scalp oils and the rosemary thing, honestly. A hair oil can make your hair feel better, look shinier, and break less, and there is nothing wrong with a comforting ritual when you are anxious about your hair. Rosemary oil specifically has one small, much-shared trial suggesting it performed comparably to a weak 2 percent minoxidil over six months, but that was for pattern loss, the study was small, dermatologists have real concerns about it, and the evidence for it doing anything for telogen effluvium shedding is thin. So enjoy your oil for what it is. I like mine. Just do not expect it to reverse a shed.

What I did, and where I have landed

The biggest thing for me was not a product. Not a supplement, not an oil. It was the moment I understood that my hair was thinning because, in my body’s read, I was malnourished. Once I really sat with that, something reframed for me. Up until that point, the whole journey had been about how good it felt to lose the weight. The hair raised the question underneath all of it, the one I had not really been asking: was I actually nourishing myself well while I did this? I shifted from only paying attention to the scale to paying attention to whether I was eating a full, balanced meal, not just chasing protein.

I started tracking my nutrition, paying real attention for the first time, including with tools like Claude and ChatGPT, specifically to make sure I was getting enough and getting variety. That shift, from “am I losing” to “am I properly supporting what my body needs from head to toe,” was the turning point for me. I added a multivitamin as insurance. I played around with extending my dosing interval a little. I redid my bloodwork. I used a hair oil, honestly for comfort, because it made my hair feel cared for, and no, I am not pretending I wash my hair often. I really do not.

I looked into minoxidil, both the topical and the oral, and chose not to use it. It just did not feel right for me. I wanted to see if my hair would come back on its own once I fixed the foundation. I want to be careful here, because that was the right call for my situation, which was a nutrition-driven shed. If you are in the pattern-loss lane, minoxidil is not the thing to skip, and I do not want my choice to read as a recommendation to wait it out when waiting is the wrong move. Know which lane you are in first.

The steadying voice through all of it was my hairdresser, who took the fear seriously instead of waving it off, and also handed me something practical to do and the genuine reassurance that it was likely to come back. For me, it really has started to. There is early growth there. It is not all the way back to what it was, though I will admit it is hard for me to judge cleanly, because somewhere in here I also started regularly coloring my hair, which is its own variable. Which feels like the right place to laugh, a little, at how relentlessly fun it is to be a woman managing all of this at once.

Where I land

If you are in the scared part right now, watching it come out and certain it will never stop, I have been exactly where you are standing, and here is what I would want said to me. The most likely story is the reversible one. It usually grows back, slowly, on a timeline longer than feels fair, and the worst moment is not the ending. Your highest-value moves are unglamorous and almost free: eat enough, eat broadly, get your bloodwork, and be patient. And if it keeps progressing past the point a shed should ease, that is your cue to go get real eyes on it, not your cue to despair.

For some of us it comes all the way back. For some of us it turns out to be the start of a longer conversation with our hair. Both are survivable, and both are easier to face with clear information than with a bottle of someone else’s certainty. I love my hair. I always have, complicated as that love is. Also, might I recommend a blowout and some epic texturizing spray?

If something genuinely helped your hair come back, I want to hear it. I am gathering everyone’s homework on this one, mine very much included.

I am not a doctor, and I am definitely not a dermatologist. This is me sharing my homework, not medical advice. I am a person being marketed to, standing in front of the same wall of pills and serums you are, trying to figure out what is actually worth it. Anything here that sounds like a plan for your body is a conversation for you and your actual doctor.

Some weeks the news is big drug data. This week it is that, plus sharing my most recent deep dive on what losing weight does to the parts of your body nobody warns you about.

This Week's Read

When I first told my brother I was going on a GLP-1, his response was, “Okay, just make sure you don’t get Ozempic face.” I said, “Yeah, of course, obviously,” as if I, or he, had a vote in the matter. But he had named a real fear. It echoed in me, and it has stuck with me to this day.

This weekend I published a piece I have been circling for months: what actually happens to your skin and body when you lose a lot of weight. The Ozempic face fear, the loose skin nobody mentions, and the honest sort through everything being marketed at us, creams, red light, microneedling, surgery, what is worth it and what is just hope with a price tag. I wrote it as a consumer, not a dermatologist, just a girl scrolling Instagram wearing her Omnilux red light mask trying to decide if I need that $80 body lotion.

[Read it here →]

Three Things I Learned This Week

1. The pill era is not coming. It is here, and it is enormous. Novo announced that the Wegovy pill has crossed three million prescriptions in about five months, roughly one filled every five seconds, which they are calling one of the strongest US launches by volume on record. Whatever you think of the number coming from the company itself, the ramp is real. The needle-free version is scaling faster than almost anyone predicted.

2. At the same time, employers are quietly pulling coverage. A new report this week found that more than a quarter of big companies are adding hoops to GLP-1 coverage, and 11 percent have dropped or plan to drop it for weight loss. Some, like Chevron, now require multiple weigh-ins a month and coaching to keep it. Globally, the share of companies covering these for weight loss fell to 23 percent, down from 30 percent two years ago. So access is splitting in two at once: cheaper cash pills on one side, shrinking insurance on the other.

3. The first serious non-GLP-1 contender showed up. Researchers in Sweden published early data on an experimental pill that works in a completely different way, revving up metabolism in your muscle instead of suppressing your appetite. In early testing it burned fat and lowered blood sugar while protecting muscle and skipping the nausea, sunds like a dream. It is very early, animal and early human, so file it under "what might come next," not "ask your doctor."

🚫 Cutting Through the Clutter: Ozempic face? Now do feet.

We have all heard of Ozempic face. But while researching this week's piece, I learned that "Ozempic feet" is now a thing too, and honestly, it makes perfect sense once you say it out loud.

Here is what is going on. When you lose weight, you lose it everywhere, and that includes the little fat pads that cushion the soles of your feet. So people are noticing their favorite shoes suddenly feel loose and cavernous, some drop a shoe size, and the soles can feel less padded, almost like walking on bone. And yes, there is already a small market ready to sell you cushioned insoles to replace the cushioning you lost.

The real takeaway is the one that runs through Saturday's whole piece: you do not get to choose where the weight comes off. Your face, your hands, your wrists, the bottoms of your feet. It all goes. That is not a mysterious drug side effect, it is just what losing weight looks like, happening faster and to more of us at once.

What I'm Hearing: live from the Endocrine Society meeting

Saturday through today is the Endocrine Society's annual meeting in Chicago, one of the biggest gatherings in this whole field, and a lot of interesting GLP-1 research is rolling out. Fair warning before I share any of it: this is all very early, presented at a conference and not yet even peer-reviewed and published, so a MASSIVE grain of salt on everything here. But now that I’m paying attention to the Endocrine’s annual meeting, a few that caught my eye:

• People on these drugs moved less, not more. A study using Fitbit data found that after people started a GLP-1, their daily steps dropped from about 5,000 to 4,500 and their real exercise fell from roughly 28 minutes a day to 22, even as they lost weight. Which is exactly why I will not stop talking about strength training and protein, and why so much of Saturday's piece keeps coming back to protecting your muscle.

• People start and stop more than anyone admits. A Boston University team looked at insurance records for more than 60,000 Americans and found about 4 in 10 stopped their GLP-1 within a year, but more than half of those restarted within the year too. Which lines up with everything I hear from you and what I wrote about in the coming-off piece. This is rarely a clean one-and-done. I am curious how this evolves once accessibility and cost are no longer massive barriers.

• Some genuinely reassuring news on the men's side. A team at Warwick Medical School in the UK pulled together five randomized controlled trials of men aged 18 to 65 and found GLP-1s do not appear to harm male hormones, sexual function, or fertility with long-term use, and in two of those trials actually improved testosterone and sperm quality in men whose low testosterone was driven by obesity. It is still a small evidence base, and these are not approved as fertility treatments, but if your person is on this ride too, that is a good one to know.

That is the week. Big pills, shrinking coverage, a humbling reminder that this stuff reaches all the way down to your shoes, and a conference full of early hints worth keeping an eye on.

(As always: I am not a doctor. Please talk to yours.)

See you next Tuesday!

Helaine

P.S. If this issue made you think of someone on the GLP-1 train or curious about it, forward this! The list grows one thoughtful share at a time.

Helaine Knapp is the founder of CityRow, a fitness company she built and scaled for a decade before selling in 2024. She is also the author of Making Waves, host of the Step Into Next podcast, and an executive advisor and coach working with founders and leadership teams navigating growth and transition. She has been on her own GLP-1 journey for nearly two years and is building something for everyone navigating this one.

helaineknapp.com · Substack · [email protected]

Making sense of the chaos, together.

As I have gone on this journey, the Ozempic face, and all the tangential versions of it across the rest of your body, has been a real part of it. We all more or less know by now that Ozempic face is not the drug doing something to your skin. It is what happens when you lose weight. You lose it everywhere. Your face. Your hands. Your feet. For me, my wrists. I have had bracelets taken in, and my rings do not fit anymore. (I learned while writing this that “Ozempic feet” is now a term. The fat pads in your feet shrink too, your favorite shoes go suddenly cavernous, and yes, there is already a market ready to sell you cushioned insoles to replace the padding you lost.) This is a different thing than “oh, I am out of those size pants.” This is the second and third order stuff of losing weight in all the places, the ones you were hoping for and the ones you never thought about.

So let’s do the real talk. Not everyone’s skin bounces back the same way. A lot of it comes down to age and elasticity, and mine has never had the best elasticity, so this is something I have struggled with for years. I am getting fed cream after cream and red light therapy after red light therapy, all of it targeted at GLP-1 weight loss, all of it something I have been curious about and quietly experimented with. So I wanted to dig in.

Here is where we are going:

• What is happening, and why

• Why it is different for women and men

• What is being pitched to us

• What is actually worth it

• What I am doing

Two things before any of that. First, none of what follows is required. This is the second and third order stuff. I personally find it interesting, and I want a good reason to say yes or no to what is being marketed to me. But unlike the question of whether to prioritize protein, this is far from a to-do list. Second, I am not a doctor, and I am also not a dermatologist, not even close. I am a person being marketed to, standing in front of the same wall of creams and gadgets you are, trying to figure out what is actually worth it. And I will be honest that I wrestle with this one, because I am as captivated by the cream-after-cream pitch as anyone, and I also believe, all the way down, that bodies are not problems to be solved. Holding both of those at once is hard. But alas, as we got into in the stigma piece, we are conditioned to be this way, right?

What is happening, and why

When you lose weight, you are hoping to lose fat. But as the fear correctly suggests, you also lose some lean tissue. Every kind of weight loss causes some lean loss, which is exactly why we are all in on protein and resistance training, to protect your muscle and bones and keep the loss focused on fat. There is much more on that in my protein paradox deep dive, so I will get off the soapbox and back to the skin.

Here is the part that actually drives the skin question. Fat and lean tissue sit under your skin. When they are gone, the skin that was covering them does not always shrink to match. That is the loose skin, the crepiness, the volume that used to be there and now is not. How much of it you get, and whether it firms back up, depends on a lot. That is what the rest of this is about.

Why it is different for women and men

We do not all start from the same place. Estrogen is one of the things that keeps skin thick, elastic, and actively producing collagen, and the numbers on what happens when it drops are genuinely startling. Women can lose up to 30 percent of their skin’s collagen in the first five years around menopause, then roughly 2 percent a year after that. The exact same amount of weight, lost at the exact same speed, can land completely differently on two bodies depending on age, hormones, and where someone is in that timeline. Men also tend to hold up a little better in the arms and legs. None of this is vanity. It is the actual biology, and it belongs in the founding principles of this conversation, not a footnote at the bottom.

What is being pitched to us, and what is actually worth it

Now the part with an entire economy behind it, aimed at this exact moment of insecurity. What is actually being marketed at me is mostly creams, red light, microneedling, and whatever the internet has decided this week. I am going to sort it by what the evidence says, and by one distinction I am going to keep coming back to, because it matters more than any single product: face skin and body skin are not the same problem. Here is the quiet tell underneath all of it. Almost every study you will see was run on the face. So for each thing below, it is worth asking two separate questions. What does it do for your face, and what does it do for your body. The answers are usually different.

Creams and lotions

Instagram is convinced I need several, and the targeting has gotten specific. There are now entire “GLP-1 skin recovery” bundles built and sold to people exactly like me, with copy promising your skin, and your selfies, will thank you. The luxury end leans on growth-factor and peptide stories, your Augustinus Bader with its proprietary TFC8 complex (I’ve bought this one 😅) , your OneSkin, your Alastin, all priced like an investment and sold on words like regeneration and firmness. The drugstore end is a wall of retinol body lotions and firming creams for fifteen to forty dollars. The word “firming,” it is worth knowing, is not regulated. Anyone can print it on anything.

So here is the honest version of what is actually in the jar. Hydration is real, and well-hydrated skin genuinely looks and feels more supple, so drink your water and yes, moisturize. On the actual actives, retinoids and vitamin C are the two ingredients with real clinical support for collagen, retinoids strongest. Peptides are a more supplementary category with softer evidence, and topical collagen, despite being slapped on every label, does not rebuild your collagen. The growth-factor luxury creams are pleasant, well-formulated moisturizers with a science-forward story, and the evidence that they firm anything is thin.

Now the face versus body split, because it is the whole game. Almost all of that ingredient research was done on facial skin, where the good actives are modest but real. On the body, the skin is thicker and less responsive, the studies are thinner, and none of it puts back what is gone underneath. Here is the line to tape to your mirror: a cream can smooth and hydrate, on your face or your body, but it cannot fix loose skin on either. What you are buying, at best, is better texture and good hydration. What you are being sold is a tightened body. Those are not the same purchase.

Red light therapy

This one is pitched to me constantly, and it is the clearest example of the face-body split. It works, in theory, through photobiomodulation: specific wavelengths, usually red around 633nm and near-infrared around 830nm, that nudge the energy centers of your skin cells and, the thinking goes, prompt more collagen.

On the face, there is at least some real evidence, and the better devices have studies behind them. The AAD says research suggests it can soften fine lines and smooth texture, and the most-credentialed at-home brand, Omnilux (which I do have), points to dozens of peer-reviewed studies and a long history in dermatology offices. But read the fine print, because two things are true at once. The independent trials mostly show improvements in things like fine lines and periorbital wrinkle depth, which is skin quality, not loose-skin laxity. And across the wider category, a lot of the studies are small, manufacturer-sponsored, and not standardized across devices, so the cheap mask is not the studied mask.

On the body, and specifically for the loose skin we are actually talking about, there is essentially nothing. A home LED mask is not the right tool for real sagging, and no honest reading of the trials supports it as one, because the light cannot reach the deep structural layers. The body panels and wraps exist, but the evidence that they tighten a loose abdomen is not there. So read red light as a face skin-quality tool that, with a legitimate device and real consistency, can modestly help tone and fine lines. Not a tightening fix for your stomach or your arms. (States the girl who wears her Omnilux mask daily.)

In-office devices

This is where the buzziest names live, and where the bill climbs fast. A few worth knowing, because you will hear all of them:

Morpheus8 is the one you will hear most. It is radiofrequency microneedling, tiny needles delivering RF energy into the deep skin, and it is the closest thing to a workhorse for weight-loss skin laxity because it has both a facial and a deeper body applicator, so it is one of the few that crosses from face to abdomen and arms. Ultrasound lifting, Ultherapy and the newer Sofwave, heats deeper layers to lift, with little downtime but real discomfort. Then there is the volume side, because a lot of “Ozempic face” is lost fat, not loose skin. Sculptra is a biostimulator, not a filler, that prompts your own collagen gradually, lasts a couple of years, and runs roughly three to six thousand dollars for a series, while hyaluronic acid fillers give instant volume. And on the body, muscle-stimulating treatments like Emsculpt get layered in for tone.

Here is the honest read across all of it. These reach deeper and do more than anything you can do at home, with modest tightening over several sessions, somewhere from several hundred to a few thousand dollars each, and a full clinic plan is usually a combination of three or four of them, which is how a “treatment” quietly becomes a five-figure project. Face versus body again: the face and neck are where the studies, the toolkit, and the real if modest results live. The body evidence is much thinner, providers themselves will tell you no non-surgical device delivers a surgical result, and even the honest practitioners will say plainly that non-surgical tightening can improve texture and mild to moderate laxity but cannot remove significant excess skin. For significantly loose body skin, none of these are the answer, no matter how the before-and-afters are lit.

Time and the free basics

Protein, resistance training, sun protection, and patience. For milder laxity, especially on more elastic skin, this is often the whole answer, and it is the one most compatible with not treating your body like a problem. Skin retracts on its own, slowly and only partway, so the standard advice is to wait six months to a year at a stable weight before paying for anything, because some of it tightens for free. This is the one I am trying to focus on for my body. (My face is a whole another plan. I have been rocking the same facialist for over 20 years, ask me about her.)

And then there is surgery

This is its own much larger conversation, and honestly its own rabbit hole. It is the only thing that physically removes excess skin, so it is the real answer when the laxity is significant, the kind where you can pinch and grab a fold. There is no magic number for when it enters the picture, but surgeons tend to talk about it after major loss, often around a hundred pounds or more, and they care more about whether your weight is stable than the exact figure. It is expensive, anywhere from several thousand to tens of thousands of dollars depending on what you do and where, and it is deeply individual. If you are going to even explore it, go in knowing it is a real decision you will spend serious time researching on your own, ideally with a board-certified plastic surgeon. I am not going to pretend to be your guide through that one. It is past what I can cut through from where I sit.

What I am doing

I live almost entirely in the free-basics tier with my Omnilux mask. Protein and resistance training first, because that is the lever with the best return and the one fully in my control. A good moisturizer, because I like one and because hydration is real.

Recently I did succumb to the marketing and after some research bought Nécessaire’s The Body Retinol, around fifty dollars, which packs the actives that actually have evidence, encapsulated retinol, an AHA, a little vitamin C, into a body format. If I was going to spend on one active thing, I wanted it to be the one with the homework behind it. The second is Augustinus Bader’s The Body Cream, which is the splurge, closer to a hundred dollars, and I will be honest that I bought it as a very nice moisturizer I would actually use and because I’m curious, not because I believe its growth-factor complex is going to wildly change anything. One purchase for the evidence, one for the pleasure, both with my expectations set low. I also use a red light mask on my face, my Omnilux, and have for a couple of years, well before any of this. I honestly cannot tell you exactly what it is doing, but it is one of the few with real studies behind it, I am consistent with it, and so I am not about to stop. I just started some of the newer body lotion things and will report back!

Overall, this is a tough one to sort through for me. Outside of saying yes or no to the creams or the random internet trends, I am still in the waiting game, letting time do its unglamorous work, balancing the part of me that reads every before-and-after against the part that does not think my body needs fixing. If something has genuinely worked for you, I want to hear it. I am gathering everyone’s homework on this one, mine included.

One more thing worth naming

This corner of the market is barely policed. There is an enormous, fast-moving industry of creams, gadgets, and procedures racing to meet millions of suddenly self-conscious people, and a lot of it sells a certainty the science does not support. The unnamed “clinic.” The “clinically proven” with no study attached. The serum priced like it can do a surgeon’s job. None of it is illegal. Most of it is just hope with a price tag, and the insecurity is the product. I have fallen victim many times over. Our best protection is knowing which rung of this ladder a given thing actually lives on, and refusing to pay surgical money for cream-level results.

Where I land

Every body is genuinely different here, age, genetics, elasticity, how much and how fast you lost, so two people can do everything the same and still land in different places. For some people this is a non-issue, and if that is you, I am thrilled, but still, eat your protein. The skin part is optional, it is yours to address or to leave entirely alone, and either way you get to decide with clear eyes instead of from fear. The most radical option on the whole menu might be doing nothing, and notice that it is the only one nobody is trying to sell you.

The thing people ask me about almost as often as their skin is their hair. That one has a surprisingly reassuring answer, and it is getting its own piece soon.

I am not a doctor, and I am definitely not a dermatologist. This is me sharing my homework, not medical advice. Anything here that sounds like a plan for your body is a conversation for you and your actual doctor.

Making sense of the chaos, together.

Today marks my eigth newsletter. I cannot quite believe I have been doing this for almost two months. If you missed Friday's Substack, I wrote a longer reflection on what I have learned in these eight weeks of writing, including why I started this journey, the rabbit holes I fell into, the survey themes that have emerged, and what I have decided I am definitely not going to build. You can read it here.

A lot happened this week. The American Diabetes Association held its annual Scientific Sessions in New Orleans (yes, it is a diabetes conference, but these drugs started as diabetes drugs, so ADA is still where the biggest GLP-1 data drops happen). And boy, did the drops happen…the pipeline is exploding!

Also, Eli Lilly's CEO sat down with Scott Galloway who feels strongly the GLP-1 innovation is bigger than AI, a bold but interesting statement. And there is a real question about what it’s like to take a break from these drugs and how best to restart.

🔬 The pipeline is about to get a lot more crowded

If you have finally figured out the difference between Ozempic and Wegovy, that Mounjaro and Zepbound are technically the same drug, that there is now a Wegovy pill, and that an oral one called Foundayo also recently launched, then get ready. The next wave is bigger and coming in fast.

Here is the field guide to what is coming.

A few things to highlight from the chart.

Retatrutide is the headliner, and it is also a real outlier on side effects. At the highest 12mg dose in TRIUMPH-1, 42% of patients reported nausea, 25% vomited, and 11.3% discontinued due to side effects (more than double the placebo rate), all meaningfully higher than what we see with Wegovy or Zepbound. Resting heart rate also rose 5-10 bpm on retatrutide compared to 2-4 bpm on the existing drugs, driven by the glucagon piece of the triple agonist. And there is a growing TikTok conversation about mood and dopamine effects (anhedonia, dampened libido) that is not yet in the trial data but worth watching.

CagriSema is Novo's answer to retatrutide, but it's a different efficacy tier. This is the comparison worth being precise about. In the REDEFINE-1 Phase 3 trial, CagriSema delivered roughly 20.4% mean weight loss at 68 weeks. That is essentially the same as Zepbound (around 21% in SURMOUNT-1) and meaningfully ahead of injectable Wegovy (around 15% in STEP-1). What CagriSema is not doing is matching retatrutide's 28-30%. So the right read is: CagriSema matches Zepbound on efficacy with a different mechanism (semaglutide plus the amylin hormone for fullness), while retatrutide is in its own tier. Phase 3 data in type 2 diabetes was published over the weekend in The Lancet and presented at ADA's Scientific Sessions in New Orleans, and CagriSema was filed with the FDA in December 2025.

Pfizer and Amgen are the first real outside challengers to the Lilly-Novo duopoly. Both companies are developing monthly shots, meaning twelve injections a year instead of fifty-two. Pfizer is further along (their Phase 3 trial is running now) and uses a single-target GLP-1 with a different signaling mechanism designed to minimize side effects. Amgen's MariTide is a dual-target drug attached to an antibody, which keeps it in the body longer. NBC News had a good explainer Friday. If these work, they reshape the entire conversation about adherence, meaning the share of patients still taking the drug as prescribed, which currently drops from 65% at four months to 34% at one year.

Survodutide and elecoglipron are the wildcards. Survodutide (Boehringer + Lilly) had standout data this weekend showing it preserves lean mass better than expected and normalized liver fat in 60% of patients with fatty liver disease at 48 weeks. Elecoglipron is AstraZeneca's entry into the category, adding another big pharmaceutical player to a space that, until very recently, was a two-horse race between Lilly and Novo.

We are at the start of what looks like a new wave of drug classes hitting all at once. Different mechanisms. Different delivery formats. Different price points. The drug you and I are taking in 2030 is almost certainly not the drug we started on, and now we can start to see exactly why.

One more thing worth flagging... CBS News published an investigation Monday morning finding that retatrutide, which is not FDA-approved, is being prescribed openly by more than 50 clinics across the country, plus 120-plus websites selling it. Eli Lilly had to publicly state that "anyone purporting to sell retatrutide for human use is breaking the law." That is not a normal sentence for a pharmaceutical company to have to say about its own pipeline drug. 🤯

🎧 What I'm Listening To

Scott Galloway and David Ricks on Prof G: "Why People Are Losing Faith in Healthcare." Released this week. About an hour. Worth the listen.

A few moments that stayed with me.

Galloway pitched GLP-1s as potentially more transformative than AI, and Ricks agreed. This has been one of Scott's predictions for over a year now and I think he is making a real point. As someone who is genuinely obsessed with AI (token-maxing daily, fully on board, will not shut up about it), I also see his case. GLP-1s are not just a weight loss story. They are a metabolic story, a cardiovascular story, a cognitive story, and possibly an addiction story. If even a quarter of those applications hold up in trials, the category becomes one of the most consequential drug discoveries of this century, affecting GDP, healthcare spend, food, fitness, beauty, and a dozen industries downstream.

Ricks was honest about the pricing problem. Galloway pressed him on why these drugs cost roughly ten times more in the US than in other countries. Ricks did not deflect. He acknowledged that the US system pays for innovation that the rest of the world then benefits from, and that this is not sustainable. He also pointed to the federal agreements that are starting to reshape access (the Medicare GLP-1 Bridge launches in 23 days, by the way).

He talked about unregulated peptides as a real problem. This was striking given the CBS investigation that dropped the same week. Lilly's official position is that anyone selling retatrutide outside their clinical trials is breaking federal law, and Ricks was clear that the unregulated market is dangerous in ways the public does not yet appreciate.

The AI in drug discovery part is what I keep thinking about. Lilly is using AI to identify potential molecules years faster than the traditional R&D process. If the pace of pipeline development is accelerating because of AI, the "five new drugs coming" chart above is not even close to the full picture. There are likely many more we have not heard about yet.

🚫 Cutting Through the Clutter: Can I take a break? The honest answer.

The question shows up in different shapes. "I want to try to get pregnant, do I have to stop?" (FDA recommends stopping at least 2 months before conception.) "I need surgery and my doctor wants me off for a few weeks." "My insurance lapsed and I cannot afford it for a couple months." "I just want to take a break for the holidays / a vacation / my own sanity." "I had to pause for an injury, when can I get back on?"

Yes, you can take a break. And yes, you can come back on. But here is some clarity:

The two-week rule. Most clinical guidance is the same: if you have been off for less than two weeks, you can usually pick up where you left off at your maintenance dose. If you have been off for more than two weeks, most prescribers recommend restarting at a lower dose and titrating back up.

The reason is mechanical. The half-life of semaglutide and tirzepatide is roughly seven days, so after about three to four weeks off, the drug is essentially gone from your system. Your stomach's normal motility has come back. Your appetite signals have rebooted. If you jump straight back to your previous high dose, you risk the same severe nausea, vomiting, and GI distress that you went through the first time you titrated up. The body needs time to readjust to slowed gastric emptying.

What restarting actually looks like. For semaglutide (Wegovy or Ozempic), the standard ladder is 0.25mg → 0.5mg → 1mg → 1.7mg → 2.4mg. For tirzepatide (Zepbound or Mounjaro), it is 2.5mg → 5mg → 7.5mg → 10mg → 12.5mg → 15mg. Most people titrate every four weeks, though some prescribers move faster on a restart depending on your history. You do not always have to walk through every dose, but you almost never want to jump straight back to maintenance after a break of more than a month.

Does it still work as well? This is the question I have heard most. Honest answer: the current evidence suggests effectiveness is generally preserved after restart, particularly after short interruptions. Some people regain weight during the break, which can affect the starting point, but the drug itself does not stop working because you stepped away from it.

A specific note on pregnancy. This is the one place the guidance is firmest. FDA labeling recommends stopping GLP-1s at least two months before trying to conceive, due to limited safety data in pregnancy and signals from animal studies. After delivery, women can typically restart, but usually with re-titration from a lower dose. If you are planning a family and on a GLP-1, this is a conversation to have with your prescriber early, not last minute.

The takeaway: if you need to pause, you can come back, and it's still going to work. Do what you need to do. Live your life. Get the procedure, and the fact that this will be there on the other side is worth an exhale.

(As always: I am not a doctor. Please talk to yours.)

Talk soon,

Helaine

P.S. If this issue made you think of someone, forward it. The list grows one thoughtful share at a time.

Helaine Knapp is the founder of CityRow, a fitness company she built and scaled for a decade before selling in 2024. She is also the author of Making Waves, host of the Step Into Next podcast, and an executive advisor and coach working with founders and leadership teams navigating growth and transition. She has been on her own GLP-1 journey for nearly two years and is building something for everyone navigating this one.

helaineknapp.com · Substack · [email protected]

Making sense of the chaos, together.

As I started thinking about where to dive into next, I found myself thinking back to why I started this, what I’ve learned so far, and where I want to go next. I want to bring you guys along for that thought process.

I started this for two main reasons.

The first was that I wanted to create the place I had hoped existed but didn’t. A single home for unbiased information rooted in science that would actually help me navigate what I was experiencing on this GLP-1 journey. I am an entrepreneur who tends to build from my own human experience, so when the resource I wanted didn’t exist, it felt natural to try to make it.

The second is that the macro trends in this category are wild. Having been on a GLP-1 for almost two years, and increasingly being the person friends came to with questions, I kept staring at this industry. One day it hit me: when there is this much behavioral change happening at once, not dissimilar from what we saw in the fitness industry years ago, this is not a six-month story or a three-year story. This is a decades-long shift. That is always interesting. There is always opportunity in a change that big.

So while I worked on creating the thing I always wished existed, I also wanted to explore whether there was a thread to pull on from a business perspective. The best way to know if something genuinely supports a need is to show up and pay attention for a while. So that is what this has looked like for eight weeks. Listening, learning, and hopefully helping start a few conversations along the way.

What I have learned more than anything, eight weeks in, is a confirmation: this category and everything around it is moving a million miles a minute. Everyone is racing in. Selling you a supplement around it. Packaging it. Wrapping a service around it…and that is all before insurance even enters the chat 😅

This is my eighth Substack post. On Tuesday I will send my eighth newsletter. The cadence has also been a brand-new practice for me. I have sent monthly investor updates for years, but writing two pieces of content a week, in front of a real audience, on a deadline, with no scaffolding behind me, is a different thing. I have built and sold a company. I have written a book. I host a podcast. I had never written a newsletter or a Substack before. Doing both twice a week has been hard, insightful, and so much learning, all at once. It has also looked like late night editing sessions that felt a little too much like cramming for a paper due the next morning. Even that has been a fun challenge to rise to.

The rabbit holes have been the best part

I went in thinking I would be writing about what was new in the GLP-1 world. What I did not expect was how many other fields I would end up wandering into. For example…

The history of how women’s bodies have been pathologized as a behavioral problem, when we now know meaningful chunks of weight regulation live in our brain biology. The actual science of what these drugs are doing (not just appetite, but inflammation, addiction circuits, cardiovascular, cognitive). The pricing landscape, which is genuinely insane and varies by literally hundreds of dollars depending on which door you walk through. The protein wave and what is real about it, why it deserves its place as the hero, and what is marketing. The supplement category and the wraparound industry that has sprung up around everyone on these meds in under a year.

It has felt like drinking from a fire hose. And the more I read, the more I realize we are still in the very beginning of the first inning.

What I didn’t expect

I didn’t know exactly what I was getting into when I started, but I had a feeling I would hear interesting stories. I had a feeling I would learn a lot. The rest of it has surprised me.

I didn’t expect that doing this would push me to use AI in a new way. Early on, as I was navigating my own questions, I realized that the way I was talking to AI about dosing, nutrition, and side effects was not something a lot of people were doing yet. I figured some guidance there might be useful, so I built my first AI tool. A copy-and-paste nutrition coach prompt that I now use myself and share with anyone who wants it. It was the first piece of code I have ever deployed myself, and that felt cool. [Link.]

I didn’t expect a friend to ask me to be a guest on her podcast to talk specifically about how people are actually affording GLP-1s. I have been a guest on dozens of podcasts. I host my own. But this was the first time I was joining a conversation from this new vantage point of being a deep learner inside this category. It was a great experience, and the episode will come out later this month.

I didn’t anticipate the number of people who would reach out. Sometimes to share their own experience. Sometimes to share what they are working on or building in or around the space. Sometimes just to say hi from somewhere I had not been in a long time. Every conversation has been unique, and there has been real knowledge to pull from each one.

And I have genuinely loved the replies. Email. Instagram DMs. LinkedIn messages. From people across every aspect of my life, from my first job to friends I have not spoken to in years to people I sat next to on an airplane once. I love hearing every single perspective, story, and worry. Keep them coming.

What I keep hearing

One of my early asks was that anyone on this journey or curious about it fill out a short survey. We are now coming up on a hundred responses, and a few big themes have emerged loud and clear. I am using them as a high-level compass for what to dig into next.

Three keep coming up.

How to come off the drug, when, and what happens after. The first piece I wrote on this is still my most-read Substack. The question is not going away. One respondent put it perfectly: she wants “a plan or a chart or something to follow for spacing and tapering instead of just running this as my own private test subject.” Turns out everyone wants this, whether they have started or are still considering.

The stigma of being on a GLP-1, and how to navigate telling people (or not telling them). This keeps coming back, in different shapes, from different cohorts. Younger women, older women, women whose partners do not know. It is shifting, slowly, but it is still very much here. (I wrote a piece on the stigma and boy was that a hard one.)

The strange identity shift that happens when your body is meaningfully different. Not the body itself. The relationship to it. The clothes that no longer feel like yours. The compliments that feel weird. The grief that nobody warned you about. One survey respondent wrote, “there’s a loneliness in this journey I didn’t expect, along with a completely different identity.” That sentence has stayed with me. This has come up more than I thought it would. I have not written about it yet, but it is coming.

Underneath all three of those is one bigger finding: most women say they feel “somewhat supported, but with gaps.” Almost nobody says “very supported.” Almost everyone is patching together their own support out of providers, friends, Reddit, and AI.

Where my builder mind is right now

When I first got excited about this category, I wrote a business plan in 90 minutes that had 8 to 12 different potential revenue streams. I was fired up and ready to hit GO. A good friend and fellow builder, after looking at it, said, “Why don’t you take a step back and listen a little bit more before you build?” I thought, “That sounds annoying but also smart.” So I did.

Eight weeks of showing up and listening later, my honest read is that whatever I might build is almost certainly not going to be a product. One of my first ideas was a subscription box for women starting a GLP-1: protein, hydration, creatine, the works. It sounded great in my head. In practice, it would mean a lot of operational work in a category that is changing weekly, and the more I listened, the clearer it became that people don’t want another curated box. They want to try a bunch of things and decide for themselves. (Side note for the brands building in this space: please let us buy a few travel packs to try before committing. The category is begging for it!)

So I am staying away from the next protein powder and staying in the lane of curiosity, science, the consumer voice, and unbiased information. Although if you really, really need a protein, let me know. I still have a stockpile of Pure Genius shots in my kitchen looking for a home 😎.

Community was another early idea. I am not against it. I am also not racing toward it. There are a lot of players already racing into this space, from telemedicine platforms to peptide support to whole new categories of guides helping people navigate GLP-1s, whether through telemedicine or not. The landscape is crowded and getting more crowded by the week.

There are a few other directions I am interested in that I have not swiped left on yet. None of them are pulling strongly enough to make me hit go. The most useful thing these eight weeks have done is help me say no to a lot of things while continuing to learn.

What I’m digging into next

A few things on my list, in no particular order.

The wider peptide world. If GLP-1s are the wild wild west, the rest of the peptide category is the deep abyss. The longevity world, the recovery world, the body composition world. There is so much happening that almost nobody in mainstream media is covering with rigor.

The identity shift piece. Specifically the loneliness and the new-body-old-self gap that women keep telling me about.

The intersection of GLP-1s and menopause. The biology gets more complicated for women over 40, the data is finally starting to emerge, and I may or may not have a big birthday later this year.

The skin and body composition changes that come with significant weight loss, and what actually works (and what is being sold to women that doesn’t).

If any of those sound like the piece you most want to read next, reply and tell me.

What I am committed to

Unbiased. Science-rooted. No agenda. Sharing my homework.

That is the whole posture. I am not a doctor. I am not a nutritionist. I am not a guru. I am a woman who has been on a GLP-1 for nearly two years, who has built things before, who is genuinely curious, and who is willing to put in the work to figure out what is real and what is marketing.

If that is useful to you, stick around. There is a lot more coming.

Talk soon,

Helaine

This past weekend I was at a friends’ wedding, and I found myself talking about GLP-1s more often than even I would have anticipated. Beyond a lot of very strange stories people shared with me (more on that below), one of the biggest conversations I kept having was about the secondary and tertiary effects of millions of people going on these medications and what that means for multiple industries.

We are already seeing it in the insane spike in CPG products but I think macro trends are going to get even more interesting from here, especially around what these drugs mean for the slightly older population. I am considering writing a larger trend piece on this. If you have thoughts, I would love to hear them.

🌊 This Week's Read 📝

On Friday, I decided to take a look at the supplements being pushed to support those on a GLP-1 and declutter what is potentially helpful and what is snake oil.

To name a few of the categories we dug into:

• The protein wave

• The "natural Ozempic" category

• The vitamin most of us actually need

• The one add-on to my coffee I have taken for years and am now reconsidering

• The “very popular one” two friends were talking about that I had literally never heard of

I cross-referenced what the industry is building, what is actually trending on GNC shelves and TikTok, and what the clinical evidence says.

If you have ever been served a supplement ad that felt a little off, or walked through the aisle in your favorite store wondering what is real and what is marketing, I recommend taking a quick spin through this piece.

Read the article →

📚 Three Things I Learned This Week

1. $500 prescriptions become $50 prescriptions on July 1 for Medicare patients.

In 30 days, the Medicare GLP-1 Bridge launches and changes what these drugs cost for the 65-plus cohort. Eligible Medicare Part D and Medicare Advantage beneficiaries (the prescription drug coverage programs that Medicare enrollees opt into) will pay $50 per month for Wegovy (injection and pill), Zepbound, and Lilly's new pill Foundayo, down from cash prices that have run as high as $500 to $700 a month.

The program runs from July 1, 2026 through December 31, 2027 as a temporary bridge to the larger BALANCE model that takes over in 2027.

The mechanics: the prescribing doctor has to submit a prior authorization form for weight loss specifically. Eligibility is based on BMI of 27 or higher with a related condition like heart disease or prediabetes, or BMI of 35 or higher with no other conditions required.

Two new pieces of information worth knowing if you or anyone in your life is considering this avenue:

• What you pay through the Bridge does not count toward your true out-of-pocket maximum. So it does not help you hit catastrophic coverage.

• If you are on a Part D plan (these are the specific prescription drug plans Medicare enrollees pick during open enrollment), you may need to switch plans during the next enrollment window to land on one that supports BALANCE in 2027. This is the kind of detail I am not going to pretend to be an expert on. KFF has the best plain-English explainer I have found on the program mechanics.

If you have a parent, in-law, or family member on Medicare who has been priced out of these drugs, June is the month to call their prescriber and start the prior auth conversation.

2. I read a fascinating paper that gives us a real clue about why GLP-1 weight loss plateaus.

A new study from NIH, published in Nature Metabolism on May 25, used imaging on living brain tissue in mice to identify the cellular mechanism. The drug acts on specific neurons in a small brain region called the area postrema. That activation triggers a chemical signal inside the neuron called cAMP. The amount of weight loss depends on how high and how long that cAMP signal stays elevated. Over time, the signal weakens. The drug is still binding. The downstream effect runs out of steam.

The honest caveat: this is mouse research. The provocative finding is that adding a different class of drug (a PDE4 inhibitor, which already exists for psoriasis and COPD) keeps that cAMP signal elevated and sustains the weight loss. In mice. And it sounds like some real deep medical stuff, but it’s interesting…

What I take from this is not that we have a cure for the plateau. It is that we are still very early in understanding what these drugs do at the cellular level. Which means we are still very early in understanding what combinations and refinements are possible. This category is going to keep getting better for the foreseeable future.

3. Women lose meaningfully more weight on GLP-1s than men do!

A new Johns Hopkins meta-analysis in JAMA Internal Medicine pooled 64 clinical trials and tens of thousands of patients across the GLP-1 class. On average, women lose around 11% of their body weight. Men lose around 7%.

What did not predict response: age, race, ethnicity, starting BMI, starting blood sugar. The only consistent demographic difference was sex.

The why is still being worked out. The leading hypotheses include body composition (women generally have a higher body fat percentage, which is the tissue most responsive to GLP-1 signaling), estrogen's effect on GLP-1 receptor sensitivity (supported by some data showing the gap narrows after menopause), and pharmacokinetic differences (women have lower body water, which effectively concentrates the dose). None of these are settled. What is settled is that the gap is real and consistent across the literature.

For every woman who has ever watched the man in her life stop drinking alcohol and drop 20 pounds: this one is for us 🥂

🚫 Cutting Through the Clutter: The Strange Skin Feeling Thing

Here is a very weird thing that gets talked about between friends and in small corners of the internet but is affecting more people than anyone realizes…

It is one of those side effects of being on a GLP-1 that some people experience and most people do not know how to name. There is a sensation that is genuinely hard to describe. I have experienced it. I am also having trouble describing it right now. But the way people describe it online: like the inside of their clothes does not feel right on their skin. Like a faint sunburn that does not go away. Like sandpaper brushing against the skin. Like the envelope of their body is slightly off. Like the early prickle before shingles. Like static electricity living on a patch of arm or thigh that nothing makes go away.

I agree with all of the above. And I cannot explain how weird it is when my own hand touches my own forearm and feels strange in a way that I cannot name. It is not particularly nice.

So what is this, where did it come from, and how many people are actually affected?

It has medical names. Paresthesia is the tingling version. Allodynia is when normal touch starts to feel uncomfortable. Dysesthesia is the broader "this is just off" category. All three are well-documented side effects of multiple medications and they are now showing up consistently in GLP-1 trial paperwork. Recent data from Eli Lilly's retatrutide trial showed it at higher rates than the earlier semaglutide and tirzepatide data suggested. Translation: it is more common than the initial brochure language let on.

Four leading theories on why it happens on GLP-1s:

• Direct nerve effect. GLP-1 receptors exist throughout the peripheral nervous system, not just the brain and gut.

• Rapid weight loss. Quick loss can cause transient nerve compression and sensation changes regardless of medication.

• B12 depletion. Eating less means less B12 intake, and low B12 is a classic cause of paresthesia. (More on this in Friday's supplements piece.)

• Blood sugar shifts. Particularly during dose escalation weeks.

What to do: first, we don’t freak out. This is not dangerous. It is not a red flag. It is annoying, weird, and almost universally fades after three to six months on a stable dose. Get your B12 tested. Stay hydrated. Make sure you are getting enough sodium and magnesium, especially on dose change weeks. If it persists or worsens, tell your prescriber.

So yes, this one is weird. It is very real. It affects more people than you would think. It is hard to explain. And we are going to be okay!

(As always: I am not a doctor. Please talk to yours.)

💬 What I'm Hearing

Lately I have been hearing a lot of very interesting stories. Friends are coming to me, asking questions about their own GLP-1 use, asking me if I will talk to their sister or their friend or their mom. Some of them ask me what dose they should be on. How many times do I have to tell you guys I am not a doctor? But I am genuinely loving all the stories and random questions so keep ‘em coming!

This week I heard something quite alarming. This is definitely an outlier. I heard anecdotally through a friend of a friend about someone so afraid of needles that their chosen GLP-1 protocol is to take an extremely high dose of tirzepatide once every eight weeks, ride out two weeks of being insanely sick with severe side effects, and then let the medication wear off and wane over the rest of the cycle. I am going to be honest: that does not sound great under any circumstance. For most people who have had needle issues, the first injection is the hard one and then they realize it’s a nothing burger. Also, we have pills now. I am not sure what this person is going to keep doing long-term. But I do have to applaud the creativity people are bringing to this category in 2026.

If you are reading this and trying something unusual that you have not told your prescriber about, hit reply. I want to know and will keep it anonymous or provide you with a cool alter ego name.

See you next week!

Helaine

PS — A handful of you sent me the Washington Post piece from last Thursday on GLP-1s potentially reshaping the brain beyond appetite (emotion, desire, food noise, and beyond). It is a good read. If you want the longer version of what these drugs are doing besides the weight loss, I wrote about it on Substack two weeks ago →

I literally had no idea what it was. She told me it was everywhere, all over her TikTok.

That was confusing because my algorithm is (or so I thought) so finely tuned to GLP-1s, longevity, and women’s health content that it occasionally serves me ads in a tone that feels personally hurtful. (But I also feel seen…it’s confusing). Anyway: if there’s a supplement out there trending hard enough that three of my friends know about it and somehow I’ve missed it, that’s either a glitch in the matrix or a sign the supplement industry is moving faster than even the most chronically online among us can track.

Obviously I had to know what this mystery HMB was, and then it piqued my curiosity enough to go down a much bigger rabbit hole: all these supplements being pushed at us from every direction, and which ones are actually worth it. The research was both confirming and genuinely eye-opening, and it’s already changing what I subscribe to.

Big industry picture — It’s no surprise the supplement world is going crazy. Somewhere around 30 million American adults have shifted how they get nutrients in a meaningful way, eating roughly 20% fewer calories, sometimes losing the appetite for entire food groups, sometimes losing muscle alongside fat. That’s a behavioral shift big enough to show up as a risk factor in S-1 filings from public food companies. When packaged-food execs are warning investors that GLP-1s could hit their sales, you know we’re a market.

There are now about a dozen “GLP-1 companion nutrition” categories that didn’t exist three years ago. Nestlé built a dedicated GLP-1 division. The global protein powder market alone is roughly $24 billion today and projected to nearly double by 2034. Kourtney Kardashian’s brand sells a $90 “GLP-1 supplement” that gastroenterologists say contains no GLP-1 at all.

The underlying change in behavior is real and support is always welcomed, the question is whether the specific products being sold to us are responding to that real need with a strong solution, or snake oil to the commercial opportunity.

The one rule

Everyone’s body is different. The only way to know what you actually need is to look at your own data, not at whatever your favorite influencer or smartest friend swears by. That cuts two ways and both matter.

Test your biomarkers. Mayo Clinic’s GLP-1 nutrition guidance recommends those on GLP-1’s get baseline lab testing for vitamin D, B12, iron, calcium, and magnesium before and during treatment. Not as a sales pitch. As a way to know what you’re actually low on. I take vitamin B and D because mine came back low. If yours don’t, you’re spending money on a problem you don’t have.

Track your macros against real food before you buy more food in a powder. I built an AI nutrition coach (free) that does exactly this, because almost no one actually knows how close they are to their protein or fiber target. Tracking for two weeks tells you whether you genuinely need a protein powder or whether you just need to add more chicken to the salad.

How I built this list

The list started with my gut but I did want it to be based on what’s most common according to real data so I cross-referenced three sources, and a supplement had to appear in at least two of them to make the list:

• What the industry is building (market research on the GLP-1 companion nutrition category)

• What’s actually trending (trade press and GNC’s own merchandising data on what’s selling, plus 2026 trend forecasts)

• What the clinical evidence says (a peer-reviewed joint advisory from four medical societies on nutrition during GLP-1 use, Mayo Clinic, and the Endocrine Society)

So here’s what made the cut:

The supplements fighting for our attention and money

1. Protein

The conversation: Everywhere. The global protein powder market is roughly $24 billion and projected to nearly double by 2034, exploding from powders into shakes, bars, gummies, and endless “GLP-1 formula” products. Search “protein powder” on Amazon and you’ll scroll for days.

The evidence: Strong and specific. People on GLP-1s in active weight loss should aim for roughly 1.2 to 1.6 grams of protein per kilogram of body weight per day, well above the standard 0.8. Combined with resistance training, adequate protein (especially whey) is the single most evidence-backed move for preserving muscle during rapid weight loss. In fact, the joint medical-society advisory is blunt that protein alone isn’t enough without resistance training. I went deep on all of this in my Protein Paradox article.

TLDR: Earns its place. The target is concrete and a lot of people don’t hit it through food alone, especially early in the week when appetite is suppressed. But “earns its place” doesn’t mean “buy a powder.” Food first. If chicken, Greek yogurt, eggs, and beans get you there, you’re done. Powder is for the gap, and if you find one you like in a format you enjoy! I currently throw Momentous chocolate recovery protein in iced coffee or a smoothie. I’ve tried many, many brands over the years and probably will continue to!

2. Electrolytes

The conversation: Loud, everywhere! Pitched at GLP-1 users for brain fog, fatigue, and constipation.

The evidence: More legitimate than I expected, and not really about exercise. When you eat 20% less food and drink less (you feel less thirsty on these drugs), you lose a major source of the sodium, potassium, and magnesium you used to get from meals. GI side effects make it worse. Brain fog is often dehydration plus low sodium plus low magnesium, and electrolytes genuinely help. Magnesium (glycinate or citrate) also helps get the gut moving and often help you drink more water.

TLDR: Real need, but situational, not a daily ritual. Where they earn their keep: during GI side effects, after hard workouts, on days you barely ate, or when you’re foggy. A pinch of sea salt in your water and magnesium-rich foods (greens, nuts, dark chocolate) do most of the same job. I’ve used LMNT, now enjoying Le Lick lollipops. When you’re not eating much, they can really help.

3. Fiber

The conversation: Real and growing.

The evidence: Fiber is one of the most under-consumed nutrients in the American diet, GLP-1 or not. Most people don't hit the recommended 25 to 38 grams a day, and the stakes go way past constipation (one of the most common GLP-1 side effects), fiber lowers LDL cholesterol, supports heart health, feeds the gut microbiome, and slows glucose absorption. Start with soluble fiber from food and go from there.

TLDR: The need is real and bigger than most people realize, but if you’re actually eating chia, oats, vegetables, and fruit, you probably don’t need a separate supplement. I aim to get it through food. This is also the section where the influencer-versus-your-own-gut lesson hit me hardest: three of my best friends were raving about Gruns gummies, I wanted to join the club, I tried them, and my stomach disagreed in no uncertain terms. Plenty of people love them. Their bodies are not my body. Your body is not mine. Fiber matters, prioritize food getting you most of the way, and supplements that work for you can be a great backstop.

4. Creatine

The conversation: Trending hard. iHerb’s 2026 forecast predicts it’ll see major growth this year, and GNC named it as one of the top GLP-1 supplements TikTok is amplifying.

The evidence: Solid for the general claim, creatine increases lean mass and strength, especially paired with resistance training, and it’s safe at 3 to 5 grams a day. The catch: most research is in athletes, not GLP-1 users in a deficit, and gains are smaller during active weight loss.

TLDR: Reasonable and low-risk if you’re doing resistance training. Useless if you’re not, it’s a training aid, not a couch aid. Gummy vs. powder doesn’t matter for efficacy. I take Create brand creatine gummies, but am switching to powder this summer to mix it up.

5. HMB (the one I’d never heard of)

The conversation: GNC’s merchandising exec named HMB alongside creatine and protein as a top GLP-1 supplement TikTok is amplifying, citing “impressive growth” for muscle health.

The evidence: HMB (beta-hydroxy-beta-methylbutyrate) is a metabolite of the amino acid leucine that tries to slow muscle breakdown, standard dose 3 grams a day. It’s been used for years in elderly care and hospital bed-rest settings. Meta-analyses show it preserves muscle in older adults and may prevent atrophy from bed rest. The evidence is much thinner in resistance-trained adults and limited specifically in non-elderly people losing weight on a GLP-1. So: decent science in a frail/older population, now marketed to everyone on the assumption it transfers.

TLDR: Real ingredient, real evidence in older and bed-rest populations, jury out for the average GLP-1 user. If you’re older or lower-activity, the case could be stronger. If you’re lifting and eating protein, your money’s probably better spent there. I don’t take it but let you know if that changes.

6. Multivitamin and the “test first” vitamins (D, B12)

The conversation: Steady. The pitch is “you’re eating less, so take a multi to fill gaps.”

The evidence: Reasonable as gap insurance, but testing specifically is the better move. Mayo singles out vitamin D and B12 for baseline testing, since those are the deficiencies most likely to show up and easiest to fix with targeted supplements. (One 2025 analysis found over 20% of people starting GLP-1 therapy had a nutritional deficiency diagnosed within the first year, with vitamin D the most common.)

TLDR: Again, I’m not a doctor, this just feels like a rational way to solve a problem. Get bloodwork before a multivitamin spree. Low on D or B12 (very common)? Take those. Panel comes back clean? A multi is fine insurance but not transformative. Vitamins are where people most reliably overspend on things their body doesn’t need: 86% of Americans take a vitamin or supplement, but only 21% have a confirmed nutritional deficiency.

7. Collagen

The conversation: Pitched hard at GLP-1 users, especially women, for skin and hair after rapid weight loss.

The evidence: Weak. Collagen is a low-quality protein (incomplete amino acid profile, no tryptophan), so it’s worse as a protein source than whey or most plant proteins. The skin claims are modest at best, and post-weight-loss hair shedding is usually telogen effluvium (a stress response to rapid loss and undereating), better addressed by enough total protein and not losing weight too fast, not by collagen.

TLDR: Heavily marketed to women, weak evidence. For the record, I take collagen daily in my coffee, I’ve thought of it as part of my protein puzzle for years before I even started on a GLP-1. After this research, I’m not sure I should. I might take a break and see if I notice any changes…

The villain: “natural GLP-1” supplements

This is where marketing crosses from “oversold but reasonable” into “actively misleading,” and where your money is most at risk.

There’s a whole category built on the claim that certain supplements are “nature’s Ozempic.” The big names: berberine (nature’s Ozempic), psyllium husk (poor man’s Ozempic), and premium products like Kourtney Kardashian’s Lemme GLP-1 pill, $90 a month, claiming to “naturally boost your body’s GLP-1 production.” I debunked the pickle juice version of this exact trope a couple weeks ago, and the pattern keeps repeating: take a food or compound with modest real effects, slap “nature’s Ozempic” on it, and let the marketing do the rest.

The evidence is damning. The Endocrine Society’s guidelines author, Dr. Caroline Apovian of Harvard, told CNN: “As for it being nature’s Ozempic, there’s no evidence to suggest that is true.” UCLA’s senior clinical dietitian: berberine works through a totally different mechanism (it activates AMPK, more like metformin than semaglutide) with “no conclusive evidence” of GLP-1-like effects, and “right now, it’s considered a dietary supplement as opposed to a tried-and-true medication.” Industry analysts have flatly called the “Ozempic-like” labeling inaccurate and unlawful in marketing.

The comparison to these drugs is a marketing fiction, not a mechanism. Some of these ingredients have modest real effects (berberine has legit blood-sugar and cholesterol data), but they are not natural versions of GLP-1 drugs and can’t do what those drugs do.

TLDR: The category most worth your skepticism. If a supplement is sold as a natural or cheaper version of Ozempic, that framing alone is your signal to walk away.

What I’d do today

• Foundations first. Enough protein, some resistance training a couple times a week. If those are missing, no supplement matters yet.

• Then baselines. Bloodwork (D, B12, iron, calcium, magnesium) and track your macros (use ChatGPT or Claude - and this prompt to get started!) against real food for two weeks. Until you know your numbers, you’re guessing.

• Fill identified gaps, not theoretical ones. Low on D? Take D. Hitting 90g protein against a 130g target? Get a powder for the gap. Don’t preemptively buy products against problems you may not have.

• Be ruthless about the “GLP-1 branded” markup. Same ingredient, no logo, less money. The chemistry doesn’t change because the label says Ozempic.

• Walk away from anything sold as a natural or cheaper version of the drug. Flashing red light.

The industry is responding to a real shift in how millions of us eat, and some of what they sell genuinely helps. But the only person who can tell you which products earn a spot in your cabinet is you, with your data, your gut, and an honest look at what you actually need. Your body is not their body. And no amount of influencer enthusiasm (or beloved-friend enthusiasm) changes that.

What’s working for you?

I’d love to know which supplements you’ve actually tried, which earned a permanent spot, and which ended up in the donation pile. Hit reply or comment, and tell me what’s been worth it for your body. The most useful version of this conversation is the honest one.

Talk soon,

Helaine

A lot happened this week: the two big stories stole the news show. 1) there's real data suggesting GLP-1s might help slow cancer, and 2) Lilly posted the strongest weight-loss results we've seen yet on retatrutide, the triple-hormone drug coming down the pipeline. Then a fun myth-bust: does the drug really have a 7-day shelf life and what’s all this social media talk about “maximizing” your shot?

But first, I was on a podcast this week about how people are actually affording these drugs and where they're getting them. It was such a good conversation that I went deep and turned it into a full Substack.

Let's get into it.

🌊 This week's deeper read: what a GLP-1 actually costs, and where people are getting them

For me, my new substack piece finally clarified the whole confusing landscape: insurance, telemedicine, direct-to-manufacturer, and the gray market, and who actually pays what across all of them.

The short version: a month of medication costs between $1 and $5 to make, and somewhere between $25 and $1,000 to buy, depending entirely on who you are and how your insurance feels that day 😅

The substack is the honest map:

• What these drugs really cost to make, and where the other ~$960 goes

• Why the US pays multiples of what every other country pays

• The six ways people are actually getting it and paying for it right now

• Four moves to make if your insurance gets finicky or flat-out denies you

• When the costs will come down dramatically and why

📝 [Read it here →]

🧬 Big story #1: real data on GLP-1s and cancer

This is the one you'll see everywhere this week. A suite of four new studies profiled by the WSJ suggests GLP-1s may affect cancer outcomes, not just weight. Here's what's real:

• In a Cleveland Clinic study of 10,000+ early-stage cancer patients, those on GLP-1s were less likely to see their cancer progress. In lung cancer, progression to advanced disease was cut roughly in half (10% vs 22%). Breast cancer showed a similar split (10% vs 20%).

• A separate analysis of 137,000+ breast cancer patients found 95% of GLP-1 users were alive after five years, versus 89.5% of non-users.

• Another study of nearly 95,000 women found those who'd taken a GLP-1 were about 25% less likely to be diagnosed with breast cancer in the first place.

• The honest caveat: every one of these is observational, not a controlled trial. People on GLP-1s tend to have better healthcare access and follow-up, which can independently improve outcomes. This is a powerful signal, not proof.

TLDR: this is real and genuinely exciting, and you should ignore any headline claiming these drugs "cure" or "prevent" cancer. We're at the "this absolutely deserves a real trial" stage, not the "settled" stage. Worth watching closely. (Notably, neither Lilly nor Novo is even studying this yet.)

💉 Big story #2: the strongest results we've seen yet (retatrutide)

Lilly posted results for retatrutide, an experimental triple-hormone drug (it hits GLP-1, GIP, and glucagon, three targets instead of the one or two in the drugs we have now). The numbers are the highest the field has produced:

• Roughly 28% average body weight loss at the highest dose at 80 weeks, compared to about 15% on semaglutide (Wegovy) and about 20-22% on tirzepatide (Zepbound). That's a real jump over everything on the market.

• In the heaviest patients, average loss hit 30% of total body weight at two years, which is on par with what people lose from gastric bypass surgery.

• That last point is the real unlock. A weekly shot landing in the same range as bariatric surgery could change everything for people who would otherwise be headed for an operating room. IMHO, that's the headline that matters.

• On muscle: this is the question I keep getting, because some people are specifically drawn to retatrutide believing it protects muscle better. The honest answer: the glucagon piece theoretically shifts your body toward burning fat, which could spare more muscle, and the bodybuilding and biohacking world is very excited about it. But the actual body-composition data is still thin, and there's no solid proof yet that it protects muscle better than what we already have. Promising theory, real buzz, not yet proven.

• The catch: about 11% of the highest-dose group dropped out from side effects. That sounds high, but it's actually in the same band as the drugs we already use (semaglutide runs roughly 7-17%, tirzepatide 6-11%), and notably, some of those retatrutide dropouts were people stopping because they were losing too much weight, not because they felt sick. It's not approved or even filed yet, realistically 2027-2028.

Here's the part I keep thinking about and still have questions on without finding answers: Retatrutide is something people are genuinely obsessed with and understandably, it works better than the two-hormone drugs, but what’s crazy is that researchers don't actually know why hitting all three hormones does more. Theories, yes but the scientists who built it can't fully explain the mechanism. How is it 2026 and we're putting this into thousands of bodies without understanding why it works better? That's mind-blowing and, honestly, a little scary. I have to believe the research will catch up. But right now, the results are running ahead of the science.

TLDR: more powerful is not automatically more right-for-you. Even the lowest dose produced ~19% loss (matching the best current drugs) and was far better tolerated. As the lead researcher said, what matters isn't just pounds lost, it's your health over a lifetime.

🚫 Myth to bust: "your shot works the same all week"

Something almost everyone on these drugs notices but nobody really explains: in the last day or two before your next shot, your appetite creeps back and the food noise returns. This is incredibly common, so let's talk about what's actually happening: how long the shot really lasts, and how to fuel yourself across the week because of it.

These drugs are built to last a long time, on purpose. Semaglutide (Ozempic, Wegovy) has a half-life of about 7 days. Tirzepatide (Zepbound, Mounjaro) is about 5. In their natural form, these molecules would break down in your body within minutes. So scientists attached a fatty acid chain that lets the drug bind to a protein in your blood, which acts like a slow-release reservoir, parceling the medication out over days and shielding it from the enzymes that would otherwise destroy it fast. That bit of chemistry is the only reason a once-a-week shot is even possible.

But "lasts a week" does not mean "steady all week." The drug peaks about 1 to 3 days after you inject, that's your maximum-suppression window, when food is the last thing on your mind. Then it slowly tapers. By the back half of the week the concentration in your blood is dropping, and in the last day or two before your next dose, appetite and food noise tend to return. That's not the drug failing. That's just the trough of the cycle, and it makes complete sense once you see the curve.

This is also where the internet gets loud, with endless content about "maximizing" your shot, timing it, and stretching doses to 8, 9, or 10 days. On stretching specifically: it's mechanically plausible precisely because of that long half-life, the drug is still meaningfully present past day seven, which is why a lot of people do it to save money. I once accidentally had to go 2.5 weeks on a single dose and the food noise and appetite came back steadily, but anecdotally, not to 100%.There's no solid trial data telling us it works as well, so I won't tell you to do it. But the pharmacology is why it's even possible.

The genuinely useful takeaway is about fueling. The instinct is to barely eat on your peak days, when you're not hungry, and overdo it on the trough days, when your appetite roars back. Flip that. What to actually do: the days you don't feel like eating are exactly when you need to make sure you get enough protein, because under-eating during the suppression window is how you lose muscle instead of fat. The drug handles your appetite. Your job is keeping the fuel, especially protein, steady across the whole week, not just the days you happen to feel hungry.

💬 One question before you go

What are you curious about? Hit reply and tell me the GLP-1 question you'd most want me to dig into next, the thing you can never get a straight answer on. I read every single one, and the best ones become future issues.

Talk soon, Helaine

The honest map of who pays what, who’s making money, what you can do about it, and what’s about to change.

A month of Ozempic costs somewhere between $1 and $5 to make. By the time it reaches someone, it can be $900, $1,000,... or $25.

What the hell is happening in between?

I understand there is a supply chain. I understand it is complicated. But a markup of roughly 20,000% seems like it should break several laws, and somehow it breaks none?

Same drug, same molecule, same factory, wildly different bill depending on who you are and how your insurance happens to feel that day.

We all know the insurance system is a shit show. That part is not news. What I actually wanted to understand was the specific, fast-changing reality underneath it: how are different people getting these drugs right now, and what are they actually paying? Because that is the part nobody can explain clearly, people keep asking me about, and it is shifting under all of our feet.

I have skin in this. I started on a GLP-1 a couple of years ago (full story here), prescribed by a New York City endocrinologist, and the first month I paid $750 out of pocket 🤯 INSANE I now pay $449 a month for Zepbound, which is still insane, but for me it is worth it. I now get my prescription through One Medical and order through Eli Lilly Direct, the QuickPen, shipped to my door. So when I say I went down a rabbit hole on how people afford this, I am also describing my own situation. I am paying out of pocket like a lot of you, and I wanted to know if I was doing it the smart way.

I was also on a podcast earlier this week explaining how people are getting and paying for this, which sent me even deeper into the hole… and I’m glad I emerged alive. Here is what I found, and I will be honest, it is both eye-opening and completely terrifying.

This is what I am going to walk you through:

• Why a drug that costs pocket change to make costs a fortune to buy.

• The six ways people are actually paying right now.

• Why do employers even have anything to do with personal health insurance?

• What to do if your insurance gets finicky or denies you.

• How people are hacking the system when none of the official paths work.

• What is about to change the price, and what I would do today.

FYI this is about paying for GLP-1s for weight loss and the growing list of other reasons people take them. It is not about diabetes. Diabetes coverage is a completely different game with completely different rules, and blending the two just muddies the water. When I say “covered” here, assume I mean weight loss and off-label use unless I say otherwise.

Let’s go.

Does it really cost under $5 to make?

Yes. And the number reframes everything.

In March 2024, researchers from Yale, King’s College Hospital in London, and Doctors Without Borders published a study in JAMA Network Open estimating what it actually costs to manufacture a month of Ozempic. (They studied Ozempic specifically, but it is the exact same molecule, semaglutide, sold as Wegovy for weight loss. Same drug, same cost to make, different name on the box.) Their answer, with a profit margin baked in: between 89 cents and $4.73. The active ingredient runs about 29 cents. The single priciest piece of the whole thing is the plastic injection pen, at roughly $2.83.

The US list price for that same month is $968.52.

So where does the other roughly $960 go? It gets carved up by a chain of players, each one taking a cut as the drug makes its way from the factory to your hand.

The manufacturer (Novo Nordisk or Eli Lilly) sets the list price and keeps the biggest slice. These companies deserve some margin for all their R&D in my opinion, and are doing just fine, by the way. Novo Nordisk’s gross margin sits around 84 percent, and GLP-1s turned it into the most valuable company in Europe. Next come the pharmacy benefit managers, the middlemen most people have never heard of, who decide which drugs your insurance will cover and skim a percentage of every prescription. Then the insurers, who negotiate, resist, and pass the cost back to your employer and to you. Then the pharmacy. By the time the drug reaches your bathroom counter, everyone in that line has been paid, and the price reflects all of them. Not the medicine.

That is the entire story of why this is expensive. Not because it is hard to make. Because a lot of people are standing between the factory and you, and every single one of them gets a cut.

And here is the kicker that proves the point. The exact same drug, made by the exact same company, costs a fraction of the US price almost everywhere else in the world.

Americans or their insurance can pay up to $1,349 for a month of Wegovy. Germans pay $137. Brits pay $92. Same molecule, same manufacturer, a tenth of the price. The difference is not the medicine. It is that other countries negotiate as a nation and the US does not, so we absorb a price built for a system stuffed with middlemen. (Novo itself has said it keeps only about 60 percent of the US list price; the rest disappears into that chain.)

If you want the deep version of how this came to be, and it is a shockingly interesting deep dive, the Acquired podcast’s Novo Nordisk episode is truly wild.

So how are people actually paying for this every month?

The easy thing to assume is that most people get this through insurance. That used to be roughly true. The reality now is that more and more people are finding out their insurance will not cover it, and they are paying out of pocket instead. But only if they can afford to.

Employers are dropping GLP-1 weight loss coverage. The reason is blunt: these drugs are expensive, people stay on them long-term, and a big share of the workforce wants them, so the cost stacks up fast. Nearly 8 in 10 employers say GLP-1s are driving up their drug spend, and with no proof yet that covering it now saves money down the road, a lot of plans are deciding it is not worth it. I have heard from more than one person whose coverage got cut mid-journey, who now stares down a $500-plus monthly bill for a drug that was working, and who simply cannot eat that cost. For most people, an extra $300 to $500 a month is not a stretch, it is a dealbreaker. That is the norm, not the exception.

If you are trying to figure out your options, here are the top six ways I think people are getting these drugs right now, and what each one actually costs.

1. Employer insurance that covers it. If your plan covers GLP-1s for weight loss and you qualify, manufacturer savings cards can drop your cost to as little as $25 a month. If you are getting it this way: congratulations, you are currently winning the game. To qualify, you almost always need a BMI of 30 or higher (roughly 175 pounds at 5’4”, as a rough anchor), or 27-plus with a related condition like high blood pressure or sleep apnea. Expect prior authorization, paperwork, and reauthorization every several months to prove you are still losing weight. The system would like a receipt.

2. Medicaid. Roughly a dozen states cover GLP-1s for obesity, and more are being added through a new federal model in 2026. It varies wildly. If you are on Medicaid, the answer is entirely about your zip code.

3. Direct from the manufacturer, paying cash. This one is relatively new, and it is quietly becoming the path for a lot of people without coverage (it is how I do it). You buy straight from the drugmaker’s own pharmacy. Through NovoCare, Wegovy starts as low as $149 a month for the oral pill and runs $349 for the standard injection, with a limited-time $199 intro price on the lowest starter doses. Through LillyDirect, Zepbound starts at $299 and the new daily pill, Foundayo, runs $149. You simply need a prescription, and those are prettyyyyyy easy to get. The drug ships to your door. The interesting wrinkle: this is increasingly the engine underneath the telehealth companies too, which I will get to in a second. A lot of players are now competing to help you pay cash directly, which is a big part of why these prices keep falling.

There is just a little theater worth noticing... Lilly published an open letter declaring it “stands against the use of its medicines for cosmetic weight loss.” Noble. And yet the prescription path is frictionless enough that this is almost certainly how the person chasing eight vanity pounds is getting it anyway. The official stance and the actual turnstile do not quite match.

4. Telehealth platforms. Ro, Hims, and the rest. Here is the part worth understanding clearly. For a couple of years, these platforms sold their own cheaper compounded versions. Hims & Hers built a huge business on compounded semaglutide. Then the crackdown hit (more on that below), and most of them pivoted to selling the brand-name drug instead. So in 2026, a platform like Hims increasingly sits on top of the manufacturer’s brand-name supply, acting as the prescription-and-delivery arm and charging you a margin for the convenience of a fast online consult. Even Amazon jumped in this spring, launching a full GLP-1 program through One Medical and Amazon Pharmacy (cash pay from $149 for the pill, $299 for injections, same-day delivery in a lot of cities). Expect $149 to $499 a month across these platforms, bundled with a quick virtual visit. Faster and comfier than your regular doctor, with lighter medical oversight as the trade.

5. Medicare, as of July 1, 2026. This one is genuinely wild. For more than twenty years, Medicare was legally banned from covering these drugs for weight loss, thanks to a 2003 law passed in the panic after the fen-phen diet drug disaster. So every Medicare beneficiary who wanted a GLP-1 to lose weight has had exactly one option: pay full price out of pocket. That ends July 1, when the new Medicare GLP-1 Bridge program lets eligible beneficiaries get them for a $50 monthly copay for the first time in history. A few predictions: the over-65 crowd is about to get snatched, your boomer parents and aunts are about to start asking if you have heard about this Wegovy or Zepbound thing (send them my way), and if I told you I wasn’t a little worried about a generation of retirees losing muscle they can’t spare, I’d be lying. There is real research on GLP-1s in older adults and it cuts both ways: the heart and kidney benefits seem to extend even past 80, but an editorial in Annals of Internal Medicine warns that adults over 65 are uniquely vulnerable to muscle loss, and aging already strips 12 to 16 percent of muscle on its own. So, if a family member starts one in July, the most useful thing you can do is make sure their lifestyle supports it: resistance training, enough protein, regular check-ins with their doctor. I am not a doctor, but that is my honest read and what the research says.

6. Compounded versions and the gray market. Cheaper, shrinking fast, and a whole conversation unto itself. That is the “hacking the system” section.

The frame I keep landing on: paying the manufacturer directly is legit (it is what I do), but at $300 to $500 a month it is still a lot, and for most people it is simply not sustainable. Which is exactly why, if there is any universe where your employer might cover it, that is the fight worth picking.

A quick detour: why is our insurance tied to our jobs at all?

Sounds like we made a big mistake back during World War II. Add it to the list of things that era left us to clean up.

Here is the very short version and it just feels completely wild as a foundation for heath insurance….

During the war, the government froze wages to keep inflation in check, so employers could not compete for workers with higher pay. But health benefits were exempt from the freeze. So companies started offering health insurance instead of raises. Then the IRS made those benefits tax-free, which locked the whole thing in. By the 1950s, getting your insurance through your employer went from rare to normal, and the US became essentially the only developed country where your coverage is welded to your job.

None of it was designed. It is the leftover plumbing of a 1940s labor regulation, and it is a big part of why GLP-1 pricing, and frankly all drug and medical pricing, is such a mess. The drugmakers are not pricing for you. They are pricing into a tangle of employers, insurers, and middlemen that exists because of a wartime accident nobody ever cleaned up.

I am not going to pretend I know how to fix this. A lot of very smart people have tried and failed. So let’s get back to the cost, which somehow is the more fun.

What to do if your insurance gets finicky or denies you

Before anything else, find out where you actually stand. The fastest way is the manufacturers’ own coverage checkers: Wegovy’s coverage lookup tool lets you plug in your insurance plan and see whether it is covered and what tier it is on, and Zepbound has an equivalent on its site. Two minutes, and you will know whether you are fighting for a covered drug or one your plan excludes entirely. That answer determines everything below.

Then, two real moves.

Advocate for coverage. Employer health plans get redesigned every year at open enrollment, and employee demand is genuinely one of the inputs. HR teams survey staff. Companies cite recruiting and retention as a reason they add this coverage. So ask, ideally with a few colleagues asking too, ideally framed around retention. Be clear-eyed that the trend is against you right now. If it does not land this year, aim for next. One specific move: ask HR whether there is a health reimbursement arrangement or a weight-management program that includes medication. Sometimes the coverage exists through a side door nobody mentioned.

Appeal the denial, if you actually have grounds. This is the move almost everyone skips. Here is a statistic that genuinely stopped me cold: insurers issued more than 49 million claim denials in a single recent year, and patients appealed about two-tenths of one percent of them. Almost nobody fights back. And when a denial is wrong, more than half of well-documented appeals get overturned. The key phrase is “when it’s wrong.” If you meet the criteria (the right BMI, the documented condition) and got denied anyway, or got denied on a technicality, appeal, and your odds are genuinely good. If your plan simply does not cover weight-loss drugs at all, an appeal will not conjure coverage that was never there. Know which situation you are in before you spend the energy. If you do have grounds, there is tech to help: a friend of a friend’s company, Claimable, uses AI to generate evidence-based appeal letters for around $40 to $50 a case, and they have specifically helped patients appeal weight-loss-medication denials. There is also a free, NIH-funded nonprofit, Counterforce Health, that does the same thing at no cost.

How are people hacking the system?

When none of the official paths work, or they all cost too much, people get resourceful. Here is what is actually happening, reported straight, no clutching of pearls.

Stretching doses. Instead of the prescribed weekly dose, people inject less, or stretch the gap between doses, to make one month’s supply last two. The math is plausible because these drugs have long half-lives, so the medication lingers longer than the weekly schedule implies. There is not robust trial data on stretched dosing, so I cannot tell you it works as well. But mechanically, the logic holds, and a lot of people do it specifically to cut the cost in half.

Buying from abroad. This is the workaround the data actually captures. Americans have been quietly ordering from Canadian pharmacies for years, where the same Wegovy or Ozempic costs a fraction of the US price. It got big enough that at one point in early 2023, Americans made up nearly one in five people receiving Ozempic in British Columbia, enough that the province moved to protect its own supply and Novo Nordisk started lobbying Canada to shut the online sales down. Technically, importing a drug for personal use sits in a legal gray zone: generally not allowed, but rarely enforced against an individual ordering a modest supply with a real prescription. The genuine risk is counterfeit product from fake pharmacy sites, so the people who do this safely stick to CIPA-certified Canadian pharmacies that require a prescription. And here is the kicker that connects to what is coming: generic semaglutide is expected to land in Canada as early as this year, which could drop the price there below $80 a month, years before any generic is legal in the US. The cross-border gap is about to get wider, not narrower.

Compounded versions. This is worth explaining tactically, because the landscape just changed. Compounding pharmacies make their own version of a drug from raw ingredients. For a couple of years, telehealth platforms like Hims sold compounded semaglutide cheaply and at massive scale, which is how a lot of people got it for $150 to $300 a month. That mass-market model is now largely shut down: once semaglutide and tirzepatide came off the FDA shortage list, the legal basis for mass-compounding evaporated, and the FDA started enforcement. As of 2026, compounded versions are mostly only legal when a state-licensed pharmacy makes them for an individual patient with a documented medical need. Some smaller telehealth platforms still operate in this narrower lane, but the ground keeps shifting under them. People swear by this route, and a lot of them have done genuinely well on it. If you go this way, vet the pharmacy hard: ask who their dispensing pharmacy is, where they source the active ingredient, and whether they do third-party purity and sterility testing. The reputable ones publish all of it. The sketchy ones do not.

Research peptides. This is the deep end, and the riskiest by a wide margin. Vendors sell compounds like semaglutide and retatrutide as raw “research chemicals, not for human consumption,” shipped as freeze-dried powder that people reconstitute and inject themselves, using dosing math crowdsourced from online communities. It is cheaper than anything else and almost entirely unregulated. The FDA has specifically warned about vendors selling “for research” products that are clearly meant for human use. Quality is a coin flip, and you are trusting a supply chain that, by design, takes no responsibility for what is in the vial. I am not going to point anyone toward a specific source, because the whole category runs on the buyer assuming all the risk. But pretending it does not exist would not be honest, and a lot of people are doing exactly this every day.

The most honest framing of this entire underground came from a STAT News essay by Nick Dothée, who writes from his own experience using gray-market GLP-1s. His line stuck with me:

“Many of us aren’t choosing between safe and unsafe. We’re choosing between unaffordable but regulated, and accessible but risky.”

That is the truth of it. The system has not caught up to the demand, so people are filling the gap themselves. I am not endorsing any of it. But I am also not going to pretend a system that prices a $5 drug at $1,000 has earned the right to act shocked when people route around it.

What’s about to change

The good news is the price is moving, and mostly in the right direction.

Generics are coming, but not for a few more years in the US. US patents on semaglutide run to 2031 and tirzepatide to 2036, so domestic generics are years out. But generic versions are expected to reach Canada as early as this year and 160 other countries by the end of 2026, at prices closer to a few dollars a month. Which is exactly why more Americans will keep looking across the border: the global price is collapsing while the US price stays propped up. The gap is going to get more absurd before it closes, which tells you everything about how American pricing works.

Oral drugs are squeezing the price down. Foundayo, Lilly’s daily pill, is already among the cheapest brand-name options at $149 a month. More oral GLP-1s are coming, and the cheapest to manufacture will keep dragging the floor lower.

More powerful drugs are right behind. Retatrutide, Lilly’s triple agonist, posted roughly 28 percent weight loss in trial results announced just this week, rivaling surgery, and could be approved by 2027 or 2028 (I’ll cover this big time in my newsletter next week!). Novo’s amycretin is close behind. More competition tends to mean more price pressure over time, eventually.

Prices are already dropping. Novo Nordisk cut Wegovy’s cash price from $499 to $349 in about eighteen months, part of a broader deal to expand access. That is the direction of travel, even if it is not fast enough.

The practical bottom line

If you are trying to figure out your move, here is the honest order I would work through.

First, check whether your employer covers it (the coverage-checker links above take two minutes). If yes, start the prior authorization and use the savings card. Cheapest path by a mile.

If your insurance gets finicky, advocate at open enrollment, and if you were denied but actually qualify, appeal. When a denial is wrong, more than half get overturned, and almost nobody files.

If you are over 65, the Medicare Bridge opens July 1 and changes everything for the first time in twenty years. And if a family member starts, get them lifting and eating protein. Dare I say should we revive Curves?

If you have no coverage path at all, paying the manufacturer directly is the cleanest option, and it gets you the actual FDA-approved drug. It is what I do. Wegovy through NovoCare starting at $149 for the pill, and LillyDirect Foundayo at $149, are real prices most people have no idea exist. It is still a lot, and for most people it is not sustainable, which loops right back to the fight worth having: getting it covered.

And if you are going around the system, you are not alone and you are not reckless for it. Probably millions of people are doing some version of this every day. Just do your homework, be honest with a doctor even if that doctor is not the one prescribing, and know exactly what you are putting in your body.

This is not the system any of us would design. It is the inherited mess of a wartime accident, two decades of patent law, and a conga line of middlemen who all get paid out of your pocket. The most useful thing I can do is show you exactly how it works, so you can make your own call with your eyes open.

Good luck, and Godspeed.

Happy Tuesday and welcome back to breaking down all the things.

What's inside: a big week on how GLP-1s are reshaping consumer behavior (the restaurant industry is officially blinking), my most tactical Substack yet, an interesting new study on "food noise," and a myth I am shocked is even a myth that needs to be busted.

This is Issue 5. Five weeks in, I am genuinely grateful these weekly digests and the more in-depth Substack pieces (please subscribe separately there if you haven't yet) are landing for you. I am still in the early days of figuring out where this all goes. Every forward, message, DM, comment, and subscriber means something. If this issue resonates, the best thing you can do is forward it to one person who would find it useful or let me know what you want to see next.

📝 What are these drugs really doing besides the weight loss?

In my most recent Substack, I was eager to know what GLP-1s are doing alongside weight loss and how.

Spoiler: they are actually doing a lot more than moving the scale.

I spent two weeks sorting out what is actually proven, what is hyped, and what the science is still figuring out.

The short version: the settled stuff (heart, kidney, liver) is more significant than the headlines suggest. The frontier stuff (dementia, addiction, perimenopause) is more uncertain than the headlines suggest, but the trends are pointing in a positive direction, and there is plenty more under the surface.

This piece is the most tactical one I have written so far. I got curious, asked questions, and tried to lay it out the way I wish someone had done for me two years ago. It's worth a read to know what else is happening in your body and why so many people are joking that GLP-1s should be in the drinking water.

[📖 Read the full piece →]

📊 The macro story this week: GLP-1s are reshaping how we spend money, not just how we eat

Two big data drops this week tell the same story in stereo.

The BCG Center for Customer Insight released a comprehensive consumer report on how GLP-1 users are changing their spending behavior. The category demand chart tells the whole story at a glance.

Alongside, the WSJ piece this week put faces and numbers on the restaurant side. A Cornell University study of 150,000 households found GLP-1 households cut fast food spending by 8% within six months of starting the drugs. Domino's CEO Russell Weiner told the Journal: "We need to have our eyes wide open and adapt. Diets are changing."

A few details from the piece worth flagging:

• Cheesecake Factory, Texas Roadhouse, and Papa John's have now listed GLP-1 drugs as a potential business risk in their SEC investor filings. This is the first wave of public companies naming GLP-1s as a material threat to revenue. 📈👀

• The Massachusetts Restaurant Association found that half of restaurant operators in the state already report GLP-1s are affecting their business. First state-level data we have on this. HALF IS A LOT.

🧠 The science behind why people stop thinking about food

This one earned its own section.

So many GLP-1 curious people ask me what this "food noise" concept is, and I get it. Before I started, the concept was very hard to fathom. And yet the second the drug kicked in, it was a monumental change in my brain. What caught my eye here was the first study I've seen focused on this specific aspect of the GLP-1 that isn't necessarily metabolic or tied to blood work, but tied to an emotional, mental aspect of this that positively affects so many people.

A new study presented at the European Congress on Obesity in Istanbul last week is the first empirical evidence for something GLP-1 users have been saying anecdotally for years: the drugs quiet "food noise."

Food noise is the constant, intrusive thoughts about food that researchers say drive a lot of overeating and disordered eating patterns. For a lot of people it has been hard to conceptualize what it actually means, which is part of why this study matters. It is the first time researchers have seriously tried to isolate it and measure it.

And it was on my mind last week when I listened to Ezra Klein and Julia Belluz discuss GLP-1s on his podcast. Ezra described what it feels like for him to sit at a table with a bowl of Oreos: "30 to 50 percent of my mental energy the whole time we were talking would be to not eat the Oreos." Imagine what we can do when that much of our mind is freed up.

Dr. Hanim Diktas at LSU's Pennington Biomedical Research Center used a validated 5-question instrument called the Food Noise Questionnaire to measure this in 417 adults in a digital weight management program. Half were on a GLP-1 alongside behavioral support. Half were on behavioral support alone.

After one month, the GLP-1 group's food noise scores dropped by an average of 4.05 points (out of a possible 20). The behavioral-only group dropped 1.15 points. The GLP-1 group also started with a higher baseline (13.1 vs 10.7), meaning the people experiencing the worst food noise responded the most.

Worth flagging: 417 participants is a small data set, and one month is a short window. This is signal, not yet proof. But it is the first attempt to actually isolate and measure something GLP-1 users have been describing for three years. We now have a validated instrument, and that instrument will get used a lot more in the years to come. We will learn a great deal about how GLP-1s are quietly reshaping the relationship between people and food.

📚 Three Things I Learned This Week

1. The science behind the addiction signal got more concrete. Researchers at the University of Virginia and the NIH published a paper this week showing that small-molecule oral GLP-1s, like Foundayo (the new daily pill from Lilly), reach deeper into the brain than scientists previously thought, all the way into the central amygdala. That is the reward circuit driving not just hunger but craving for alcohol, nicotine, gambling, and shopping. The mouse study explains why GLP-1 users keep reporting they have lost interest in their bad habits. Human trials for addictions outside food are just getting started. Read the NIH press release →

2. GLP-1s appear to raise testosterone in men, independent of weight loss. A new study presented this week at the American Urological Association annual meeting analyzed thousands of men on GLP-1s and found median total testosterone increased from 320 to 419 ng/dL. The increase showed up regardless of age or starting BMI, and was not fully explained by weight loss. The Mayo Clinic team behind the study credits GLP-1 receptors directly in the testicular Leydig cells, plus the anti-inflammatory effect of the drugs. Another piece of the weight-independent benefits picture I am going to have to add to my [Substack on the ancillary benefits]. Medscape coverage →

3. The Wall Street Journal is officially making GLP-1s a beat. Two pieces this week alone, one in the Hospitality section on what is happening to restaurants and one in Health/Pharma on muscle loss and frailty. The muscle loss piece is the one to read this week. Up to 10% lean mass lost on these drugs, with Daniel Green at the University of Western Australia quoted in the piece saying: "We are curing obesity by encouraging frailty. It should say 'must be taken with resistance training' on the box." Reading this alongside Maine's announcement two weeks ago that the state will only cover GLP-1s for weight loss if state employees enroll in a structured nutrition and lifestyle program drives home what should be obvious by now: lifestyle changes alongside these drugs is not a nice-to-have. It is the only way they work long-term.

🚫 Myth I want to bust this week

A friend sent me this Instagram reel and asked me to debunk it. The creator (a "verified" wellness account) holds up a tub of pickles and says her "toxic trait is drinking pickle juice because the acetic acid activates GLP-1, the same hormone activated by Ozempic, to keep you fuller longer, curb your appetite and have less cravings."

I am honestly a little concerned my friend asked me to debunk this. But that is a story for another day.

Here is the precise version of what is true. Acetic acid does stimulate your body to secrete a little more of its own natural GLP-1 hormone through a receptor in your gut called FFAR2. The studies showing this are real. A 2016 review in Molecular Nutrition & Food Research lays out the mechanism, and a 2022 meta-analysis in The American Journal of Clinical Nutrition found vinegar produces a modest reduction in post-meal blood glucose.

Here is the precise version of what is wildly overstated. The amount of GLP-1 your body secretes after a shot of vinegar is microscopic compared to what a GLP-1 medication delivers. The GLP-1 your body makes on its own (called endogenous GLP-1) has a half-life of about two minutes. Semaglutide (the active ingredient in Ozempic) has a half-life of about a week. A pharmacological dose of a GLP-1 receptor agonist is not in the same conversation as a slight uptick in your body's own GLP-1 secretion from a tablespoon of pickle juice. We are talking about a few percentage points off a blood sugar spike, not 15 to 20% body weight loss.

So, if you like pickles, eat pickles. The science behind acetic acid and modest blood sugar effects is real. The framing that this is in any way equivalent to a GLP-1 medication is absurd. And the bigger issue is that when verified wellness creators with reach make these comparisons, they make it harder for people in this category to figure out what is actually true. Sigh.

🛒 What I've tried this week

Le Lick electrolyte lollipops.

If you know me, you know I'm obsessed with hydration. I LOVE water, always have, even before it was cool and required for GLP-1 lyfe.

Here is the honest version of why electrolytes matter on GLP-1s. It is not that water alone is insufficient for everyone. For most people getting enough sodium and potassium from food, plain water is fine. The problem on GLP-1s is that people are eating less, period, which means they are taking in fewer minerals overall. Sodium and potassium come primarily from food. When food intake drops, those minerals often drop with it. That is when supplementing matters, and that is when a surprising amount of GI complaints (constipation, headaches, low energy, sluggishness) start to show up.

So this is less "you need electrolytes to be hydrated" and more "if you are on a GLP-1 and not eating much, you are probably under-consuming the minerals your body needs."

Most electrolyte products are aggressive. I've gone through phases with most of them and always have a few packs lying around, especially when I'm playing tennis in the sun.

Le Lick is a lollipop. Sodium and potassium in candy form, with a sugar-to-salt ratio modeled on coconut water. Two pops is the adult dose. No mixing into a bottle of water. Easy.

I like them as a sweet treat after lunch (ideally in place of a fridge cigarette Diet Coke or Coke Zero, don't come at me). Pink lemonade and tart cherry are my favorites.

Not life as imperative as strength / resistance training. But useful. Use code HELAINE for a 10% discount.

enjoylelick.com

💬 What I'm Hearing

This past week I had more people come to me than ever before. Three groups specifically.

People considering microdosing for inflammation and longevity reasons. People starting GLP-1s for non-weight-loss reasons like cardiovascular protection or perimenopause symptom management. And people who have already started and don't yet have the full picture.

To say we are in early days for this category is generous. We are at the very beginning.

If you or someone close to you is curious and trying to figure out what to do next, I am more than happy to have a conversation. I have built a lot of AI tools around this for my own thinking, and I can leverage them to help answer your questions candidly. As a non-doctor, with the lens of someone who has been doing this for almost two years and has done a lot of reading lately.

Until next week,

Helaine

P.S. If this issue made you think of someone, forward it. The list grows one thoughtful share at a time.

Helaine Knapp is the founder of CityRow, a fitness company she built and scaled for a decade before selling in 2024. She is also the author of Making Waves, host of the Step Into Next podcast, and an executive advisor and coach working with founders and leadership teams navigating growth and transition. She has been on her own GLP-1 journey for nearly two years and is building something for everyone navigating this one.

helaineknapp.com · Substack · [email protected]

The moment I perked up about everything else was my first round of bloodwork after I started. The typical numbers looked good, but the inflammation marker had dropped meaningfully. That caught my attention.

For the first stretch, I assumed all of those positive changes in my biomarkers were a downstream result of losing weight. Which made sense. I was happy with it. I remember thinking, “this is not just about the scale, this is about being healthier in general, and I am genuinely grateful I have done this for myself.”

More recently, I’ve started to hear people talk about the drugs differently. I have friends with no real interest in changing the scale who are actively microdosing GLP-1s. I have been doing research to help people navigate insurance, and it is becoming clear that these drugs will soon be prescribable not just for obesity, but for cardiovascular health and inflammation (ideally even more in short order). I have also been reading more about my own family’s health history. Like many families, mine has a lot of cardiac issues. My dad had kidney cancer. A lot of the adults in my family are pre-diabetic. As I learn more, this thing stops feeling like a drug I am taking just for the results it had on my life today and starts looking a lot more like preventative medicine for what is most likely to come.

Inside all of that, the question I kept landing on was a simple one.

What has actually been proven? And how much of it is the weight loss doing the work versus the drug itself doing something else, independent of the weight loss?

Julia Belluz at The New York Times went deep on this exact question last month, in a piece I linked to in Tuesday’s newsletter. It is the best plain-English summary of where the science is right now, and I am going to be referencing it throughout this piece. The short version: the drug is doing far more in the body than the weight loss alone can explain.

Before we get into it, three foundational things worth knowing...

Who is Daniel Drucker, and why does he matter here?

Daniel Drucker is the closest thing the GLP-1 story has to a founding scientist. He is a Toronto-based endocrinologist credited as one of the original co-discoverers of GLP-1 almost three decades ago. He has spent his career on this drug class. When other researchers cite the science, they are often citing his lab.

What I like about him: he is all science, no fluff. Monotone in the best way. He is not trying to grow his audience on the internet. He just keeps publishing.

In January 2026 he published a comprehensive review in Nature Medicine called “The Expanding Landscape of GLP-1 Medicines.” Fair warning, it sits behind a paywall, so if you cannot get to it, the Eric Topol summary on his Substack covers the major beats. If you would rather listen than read, Drucker’s appearance on Topol’s Ground Truths podcast is the audio equivalent. From April 2024, so technically two years old, but it still slaps and it is worth 37 minutes. Or 25 minutes at 1.5x.

What does “weight-independent” actually mean?

Once again, I am not a doctor. Most of us reading this are not either. But this is the single concept that, once I understood it, changed the lens I was looking through, both for the entire class of GLP-1 drugs and for what they are doing in my own body over the long term.

Think of it like an iceberg. The scale, the weight, the visible body changes are the tip. There is so much more happening underneath that we are only starting to see.

“Weight-independent” is the phrase researchers use when a drug produces a health benefit that cannot be explained by the weight loss alone. If a person loses 20 pounds and their cholesterol drops, that is probably the weight loss doing the work. But if a person’s heart attack risk drops within months of starting the drug, before significant weight loss has even happened, the drug itself is doing something to the cardiovascular system. The benefit is independent of the weight change.

This is the most important framing shift in the entire GLP-1 story. The early coverage was about weight loss. The current science is about what the drug does in the body alongside that. They are related, but they are not the same conversation.

Drucker’s framework breaks the benefits into four mechanisms: reduction of blood sugar, reduction of body weight, attenuation of inflammation, and direct activation of GLP-1 receptors in target tissues throughout the body. Three of those four are not weight loss. That tells you most of what you need to know about why these drugs keep showing up in unexpected corners of medicine.

What are these drugs actually approved for right now?

Worth knowing the current map, because the headlines often conflate “the science is interesting” with “this is something you can get prescribed for that today.”

Semaglutide (sold as Ozempic and Wegovy)

• Type 2 diabetes (Ozempic), approved 2017

• Chronic weight management (Wegovy), approved 2021

• Cardiovascular risk reduction (Wegovy), for adults with established cardiovascular disease who are overweight or have obesity, approved March 2024

• Diabetic kidney disease (Ozempic), for adults with type 2 diabetes and chronic kidney disease

• Fatty liver disease, specifically MASH with moderate-to-advanced fibrosis (Wegovy), approved August 2025

Tirzepatide (sold as Mounjaro and Zepbound)

• Type 2 diabetes (Mounjaro), approved 2022

• Chronic weight management (Zepbound), approved 2023

• Obstructive sleep apnea (Zepbound), for adults with obesity, approved December 2024

Two notes. For most prescribing and insurance purposes, “obesity” means a BMI of 30 or higher. Some indications also allow a BMI of 27 or higher if you have at least one weight-related condition (high blood pressure, type 2 diabetes, high cholesterol). Insurance coverage varies dramatically by plan, by employer, and by which approved indication you are getting the drug for. Same drug, different label on the prescription, completely different coverage outcome. That is its own, separate, long article.

My goal in digging deeper into Drucker’s four buckets is to give us all a lens for the wild amount of information that is out right now, much of which is engineered to capitalize on clicks and eyeballs. The reality is, yes, this is a blockbuster drug class. But it is also still in its infancy, and there is a lot more research to be done.

Let’s see what is proven. Let’s see where the excitement is running ahead of the data. And let’s see where it appears to be heading.

What is actually settled?

Three areas. The trials are done. The FDA labels reflect them. The science is no longer in dispute.

Heart disease. The SELECT trial, published in NEJM in 2023, followed 17,604 adults (27.7% women) who had overweight or obesity plus existing cardiovascular disease, but no diabetes. Over an average of three years, semaglutide reduced major cardiovascular events (heart attack, stroke, cardiovascular death) by 20 percent. The patients in this trial lost only about 9.4 percent of their body weight on average. Meaningful but moderate. And cardiovascular risk still dropped by a fifth. A prespecified analysis in The Lancet in October 2025 confirmed that this protection was independent of how much weight the patient started at and independent of how much weight they lost.

Kidney disease. The FLOW trial, in NEJM in 2024, followed 3,533 patients (30% women) with type 2 diabetes and chronic kidney disease. Semaglutide reduced the risk of major kidney outcomes by 24 percent. The trial was stopped early because the benefit was so clear. Patients on the drug also had 20 percent lower all-cause mortality.

Liver disease. Specifically MASH, which stands for metabolic dysfunction-associated steatohepatitis. The ESSENCE trial, in NEJM in 2025 (and FYI 57.1% women, hallelujah!), showed 62.9 percent of patients on semaglutide achieved resolution of MASH without worsening fibrosis, compared to 34.3 percent on placebo. The FDA approved Wegovy for this in August 2025. MASH affects roughly 14.9 million American adults.

It is clear there are additional benefits showing up independent of weight loss. If weight loss is not the reason these things are happening, then what is?

How is all this good stuff actually happening -independent of weight loss?

When I hear about cardiac benefits showing up before the weight loss has even kicked in, my curious brain wants to know: okay, but what is actually doing the work? Researchers have identified several mechanisms operating in parallel. None of them are fully mapped, but the picture is coming into focus.

The drug appears to directly reduce inflammation inside the walls of blood vessels. It improves the function of the endothelium, the thin layer of cells that lines every blood vessel and is one of the earliest things to break down when cardiovascular trouble is brewing. GLP-1 receptors in the brain appear to send signals that modulate inflammation throughout the body. The drug changes the behavior of epicardial fat, the fat tissue that sits directly on the heart and is more inflammatory than regular body fat. It produces modest reductions in blood pressure and lipid levels, both of which happen earlier than significant weight loss.

In plain English: weight loss helps the heart, yes. But the drug is also independently calming inflammation in the blood vessels, improving how the cells lining those vessels function, dialing down inflammation through brain signaling, and changing the behavior of fat tissue sitting on the heart. Those mechanisms start working immediately, before the scale has meaningfully moved.

The math from SELECT only works if this is true. Nine percent weight loss does not, on its own, produce a 20 percent reduction in heart attacks. Something else is happening.

What is the unifying mechanism underneath all of this?

The thread tying most of these benefits together is inflammation. Chronic, low-grade inflammation is the common factor underneath heart disease, fatty liver, dementia, autoimmune conditions, depression, and probably parts of how we age in general.

Longevity researchers have started calling it “inflammaging.”

If a class of drugs is consistently dialing that inflammation down across the body, the seemingly disconnected benefits start to make sense as connected. The heart, kidney, and liver findings are not three separate stories. They may be three expressions of the same underlying effect.

Topol described this on his podcast as “subtle modulation” of the inflammatory system, in contrast to “blunt-force immunosuppression” like steroids. Steroids reduce inflammation by suppressing your immune system broadly, which is why they have so many side effects. GLP-1s appear to tune the inflammatory response without compromising the immune defense. That distinction matters. It is probably also part of what is behind the dementia signal, the addiction signal, and parts of the cardiovascular signal.

What are we excited about that isn’t actually proven yet?

This is where the excitement and the clickable headlines are running well ahead of the data.

Dementia and Alzheimer’s. Pooled analyses of older trials and real-world cohorts have shown reduced rates of dementia in GLP-1 users. The dulaglutide REWIND trial showed 14 percent less cognitive decline. A VA database of more than 200,000 patients showed lower Alzheimer’s and dementia rates in GLP-1 users compared to other diabetes drugs. But the dedicated Alzheimer’s trials, called Evoke and Evoke+, released top-line results showing no reduction in cognitive decline in patients who already had mild Alzheimer’s, despite some biomarker improvements. Drucker’s own conclusion: whether GLP-1 medicines might prevent Alzheimer’s before amyloid plaques even start forming is uncertain.

Honest interpretation: probably preventive, not curative. Earlier intervention probably matters more than late. None of it proven yet.

Parkinson’s. A 2024 NEJM trial of lixisenatide in 156 patients with early Parkinson’s showed motor symptoms did not progress over 12 months in the treatment group, while the placebo group worsened. Across five GLP-1 Parkinson’s trials, three smaller ones were positive and two larger ones were negative. The mechanism is not fully understood. But no drug currently slows Parkinson’s progression at all, so even modest replicable benefit would be a finding.

Addiction. This one is fascinating, and honestly one of the most interesting parts of the whole picture to me. GLP-1 users report reduced cravings for alcohol, nicotine, gambling, even online shopping at rates that have surprised researchers. The effect appears to involve direct activation of GLP-1 receptors in the brain’s reward circuits. UCSF is running dedicated trials of a newer compound for substance use disorders. The trials are just beginning, so it will be a while before we see real results on addictions outside of food. But the anecdotal signal is already there, and trend-wise, the implications are huge.

If half of these reports turn out to hold up, maybe this stuff should be in the air in Vegas. Just do not tell the casino owners I said that.

What about women? What about perimenopause? What about menopause? What do we actually know and what is speculative?

Once again, shocking news that we do not have a ton of data specifically on women in any of these age ranges. Hey, at least we still have the right to vote. 🙃

The data gap is structural, not accidental. The NIH did not require sex as a biological variable in research it funded until 2016. That is roughly ten years ago. Most foundational pharmacology and cardiovascular research was done on male bodies. The reason heart attack symptoms in women are still underdiagnosed today is partly that “typical” symptoms were defined from male data.

What we do know. A RAND survey from August 2025 found that 20 percent of US women aged 50 to 64 report current or past GLP-1 use. Women aged 30 to 49 report twice the rate of men. A post-hoc analysis of the SURMOUNT trials covering 2,542 women, published by NewYork-Presbyterian and Weill Cornell, found tirzepatide produced equivalent weight loss across pre-, peri-, and postmenopausal women. Menopause does not seem to blunt the drug.

Perimenopause, menopause, and HRT combinations. A lot of voices online are talking about the GLP-1 + hormone replacement therapy combination as a magic intersection. The peer-reviewed research here is finally starting to catch up. A Mayo Clinic study published in The Lancet Obstetrics, Gynaecology & Women’s Health in January 2026 followed 120 postmenopausal women and found that those on tirzepatide plus HRT lost about 35 percent more weight than those on tirzepatide alone (17 percent versus 14 percent over 18 months). A separate Mayo study from 2024 found the same synergy with semaglutide and HRT. Real signal, small samples, and the authors are explicit that randomized controlled trials need to follow.

The clinical world is ahead of the trial world. Dr. Mary Claire Haver, one of the leading public voices on perimenopause and menopause care, runs a clinic in Texas that treats this combination directly. She has said publicly that up to 20 percent of her clinic’s patients are on a combination of HRT and GLP-1, and recently described the rationale this way:

“Hormone therapy helps restore metabolic balance and preserve lean mass, while GLP-1s target the gut-brain axis that drives appetite and fat storage. It is a powerful combination for women in perimenopause and menopause, not for vanity, but for healthspan and longevity.”

Worth flagging: Haver’s 20 percent number is an observation from a single clinic, not a study. But it tracks with what is starting to show up in the published research.

What we do not know. Whether GLP-1s amplify or blunt the cardiovascular protection that estrogen provides before menopause and that women lose afterward. What these drugs do to bone density when women are losing weight rapidly in their forties and fifties. Their effects on hot flashes, sleep quality, mood, or vasomotor symptoms independent of weight loss. This is one I might want to go deeper on in a future piece. For now, the people doing the most credible work on adjacent territory are worth following directly: Dr. Mary Claire Haver on menopause, Dr. Stacy Sims on female physiology, and Drucker himself on the underlying drug class.

PCOS. Polycystic ovary syndrome affects roughly 6 to 12 million American women, most undiagnosed. The condition is driven largely by insulin resistance, which is exactly what GLP-1s directly address. A 2025 meta-analysis in Scientific Reports found significant improvements in BMI, waist circumference, insulin resistance, and hormone levels in women with PCOS on GLP-1s. Most of those studies were on older versions of the drug. Data specific to semaglutide and tirzepatide is still emerging.

Would you stay on it even without the weight loss?

The most striking single number Julia Belluz reported is this. More than 60 percent of GLP-1 users in her NYT survey said that if the drug failed to help the condition it had originally been prescribed for, they would keep taking it for the other benefits. People are not lobbying to stay on drugs they no longer need.

A parallel trend now: people with no diabetes and minimal weight to lose are asking their doctors for these drugs, getting them through telehealth, or microdosing using doses as low as one-tenth of the standard prescription, specifically for inflammation reduction and longevity benefits.

The most visible name in this conversation is Bryan Johnson, the longevity-obsessed entrepreneur who started microdosing tirzepatide. He is not overweight. He is not diabetic. His argument is that small consistent doses of GLP-1s may help reduce the chronic inflammation associated with aging, and he tracks his biomarkers continuously to test it. Telehealth companies like AgelessRx, Shed, and Ivim are openly marketing $99-a-month longevity microdose protocols.

The standard caveat from the medical establishment is real. There are no randomized controlled trials of microdosing protocols. The trials were done at standard doses. Anything below that is extrapolation. Even Eric Topol, who is otherwise one of the most enthusiastic voices on the GLP-1 class, has called the microdosing trend a “craze” that is “not substantiated.”

Here is where I land. If you are someone who has gotten to the point of considering microdosing GLP-1s for the ancillary benefits, you have probably already done a good amount of your research. You are probably pretty far along on your personal health understanding. Honestly, at this point, if that is something you want to try, I do not see a lot of downside. I am not opposed to it. Given how wildly important reducing inflammation can be for a million different things, why not try and see if it helps you?

What about the side effects?

None of this means these drugs are without trade-offs. The gastrointestinal effects are real. The gallbladder events are real. Muscle loss when protein and resistance training are not in the picture is real. Hair loss when weight loss happens too fast is real. The cost is real. The fact that you may need to stay on this indefinitely is real.

A dedicated side effects piece is coming in this newsletter in the next few weeks. This one is about what the science is telling us the drug may be doing for the people who tolerate it well. The trade-offs deserve their own conversation.

So who should actually be on this?

Back to the question I keep coming back to. Should everyone be on this? Should it just be in the drinking water?

Probably not everyone. But probably more people than are currently getting it. Especially people with cardiovascular risk factors. Especially people with metabolic syndrome. Especially people with a family history of kidney disease, cardiac disease, or dementia. Especially people with persistent low-grade inflammation showing up in their bloodwork.

So back to Belluz’s question. Would I stay on this forever, even without the weight loss benefits?

Probably, yes.

I do not really have side effects. The biomarkers in my bloodwork keep moving in the right direction. And the more I read about cardiac history, kidney health, and inflammation in my own family, the more this stops being a weight loss decision for me and starts being a preventative medicine one. That is the conversation I am quietly starting to have with my brother and cousins, even the ones who are not focused on the scale.

The drugs are way ahead of the system that is supposed to help us decide what to do with them. So in the meantime, we are doing the homework on our own. That is what this newsletter is here for. Copy mine, share yours, and let’s figure out what the right questions are together.

Helaine

P.S. If this resonated, send it to one woman who needs to read it.

I’m Helaine Knapp. I’ve been on a GLP-1 for almost two years and I’m still figuring it out alongside you. I built CityRow before this, sold it in 2024, and started writing because the information in this space is moving faster than anyone can track and women deserve a calmer voice in it. I’m also a coach, advisor, the author of Making Waves and host of the Step Into Next podcast.

Substack is where I write the longer essays. The newsletter, on Beehiiv, is where I land in your inbox every Tuesday morning with what’s actually worth knowing, every week. Get on the list here.