A gloved hand holding an empty orange prescription vial against a pale marble background

How Do I Switch From Compounded Semaglutide or Tirzepatide to Wegovy or Zepbound?

On November 6, 2026November 5, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

The short answer: you switch by getting a new prescription for Wegovy, Zepbound, or one of the new pills, and your prescriber picks the starting dose. A compounded dose does not convert cleanly to a brand dose, so the number on your old vial is a clue rather than an instruction.

If you have been off for more than a couple of weeks, or nobody can tell you exactly what was in your vial, the safest default is to restart near the bottom of the label schedule and climb. That costs you some weeks. Guessing high can cost you days of vomiting.

Why your compounded supply is drying up

Pharmacies were allowed to copy semaglutide and tirzepatide while the brand products were in shortage. The shortages ended. FDA declared the tirzepatide shortage resolved on October 2, 2024, confirmed that on December 19, 2024, and declared the semaglutide shortage resolved on February 21, 2025. The enforcement grace periods for state-licensed pharmacies and outsourcing facilities then closed in steps through the spring of 2025 (1).

2026 has added pressure from the other direction. FDA’s April 1, 2026 update says plainly that tirzepatide and semaglutide are on neither the 503B bulks list nor the drug shortage list (1). On April 30 the agency proposed excluding semaglutide, tirzepatide, and liraglutide from that bulks list permanently, with a comment period that closed July 30 after an extension (2). And on March 3 it sent warning letters to 30 telehealth companies over marketing that implied their compounded products were the same as approved ones (3). As of early November 2026 there was no final decision on the bulks proposal, so treat that piece as pending.

A narrow lane survives. FDA will not treat a compounded product as essentially a copy when a prescriber determines and documents a change that makes a significant difference for an identified patient (1). It also says a semaglutide plus B12 product can still be judged a copy when both strengths fall within 10 percent of the commercial products (1). If your supplier is shipping less, relabeling, or closing its compounded program, this is the reason. It is a regulatory story and says nothing about you.

I covered the safety checklist and the history in Compounded Semaglutide and Tirzepatide: What to Know Now. This post is the practical follow-up for someone who has to make the move.

Why can’t I just convert my compounded dose?

Because the label on a compounded vial and the label on a pen are written in different languages, and sometimes describe different molecules.

Start with units. Compounded product usually arrives in a multi-dose vial that you draw up with a syringe. A poison control case series in the Journal of the American Pharmacists Association described three patients with adverse events after compounded semaglutide, two of them 10-fold dosing errors, and one who was dosing in milliliters and units instead of milligrams. One needed an antiemetic and intravenous fluids (4). A pen clicks to a fixed dose. A syringe asks you to do arithmetic.

Then the ingredient. FDA states that semaglutide sodium and semaglutide acetate are different active ingredients from the one in the approved drugs, and says it knows of no lawful basis for using those salts in compounding. It has also logged reports of patients getting more product per dose, dosing more often, or titrating faster than the label allows (5). As of May 31, 2026, the agency counted 990 adverse event reports tied to compounded semaglutide and more than 730 tied to compounded tirzepatide, and it says underreporting is likely (5).

So a compounded vial labeled “2.5 mg weekly” and a Zepbound 2.5 mg pen share a number. They do not share a guarantee.

Restart low, or match the dose?

No label tells you how to switch from a compounded product, because none of them contemplate it. What the labels do tell us is how to restart after a gap, and that is the closest evidence we have.

The Wegovy label says that if two or more consecutive weekly doses are missed, reinitiate dose escalation at a lower dosage to reduce the risk of gastrointestinal adverse reactions (6). The Zepbound label addresses only a single late dose (7), but Lilly’s medical information page describes what the SURMOUNT trials did: after one or two missed doses, treatment restarted at the same dose if it had been well tolerated, and after three or more, it restarted at 5 mg regardless of the prior dose (8). The Foundayo label sets its trigger at seven or more consecutive missed daily doses, again with reinitiation at a lower dosage (9).

Read together, gap length is the first variable. A short gap on a known, well-tolerated dose makes matching defensible. A longer gap pushes you down the schedule. The second variable is certainty. If the pharmacy is unknown, the concentration is unclear, or the patient cannot say how many units they drew, leaning low is the safer choice. My view is that the two errors are not symmetrical. Starting too low delays the result by a few weeks. Starting too high can mean days of vomiting and, rarely, a trip for fluids.

For scale, here is what low looks like. Wegovy starts at 0.25 mg and reaches 1 mg at week 9, with each step lasting four weeks. Zepbound starts at 2.5 mg and reaches 5 mg at week 5 (6,7). The Wegovy label also allows delaying escalation by four weeks if a dose is not tolerated (6).

There is no single number I use. If someone has been getting their medication through a reliable compounding pharmacy, that helps, because there is likely to have been no gap in dosing. If the pharmacy is unknown, or there is some question about how they have felt on the compounded drug, I adjust. Where I start depends on how the patient is doing, which pharmacy and which medication they were using, and whether they have been sick to their stomach or have seen no change in their hunger at all. If they were having side effects on the compounded product, such as nausea bad enough to need a lot of ondansetron, or severe diarrhea or constipation, but they want to try a brand-name medication to see whether that improves, I start them on a lower dose than they were taking. If they have been on a particular compounded dose for a long time and are not losing any weight, I might start higher than the label’s starting dose. It really depends.

What I would gather before the video visit

On a video visit I cannot pick up the vial, so the vial has to come to me as photographs. The useful list is short: the pharmacy label showing drug, concentration, and lot; the syringe type; how many units the patient draws; the date and size of the last injection; the highest dose reached; and every side effect along the way. Patients who bring that make the dose decision easy. Patients who bring “it was the blue one” make it a judgment call.

What I ask for is a photo of the current prescription. It has to show the name of the medication, the dose, the date it was prescribed, and the prescribing doctor. It also has to show any additives, because compounded versions sometimes include them, and I want to see exactly what has been in that vial.

What restarting will feel like

Expect the early weeks of a new start, even if you were on a high dose before. The labels build their escalation schedules specifically to reduce GI side effects (6,7), and tolerance you built on a product of uncertain strength is not a reliable credit. Nausea, early fullness, and constipation are the usual complaints. If a step is rough, hold there rather than push, which the Wegovy label explicitly permits (6).

Some patients feel like they are going backward when the dose drops. They are not. The goal is to land on a dose you can verify, then climb to the effect you want. Persistent vomiting, or an inability to keep fluids down, is a reason to call. My side effects post has the incidence numbers.

What will the brand version cost?

Less than many people expect, though prices move. As I write this, NovoCare lists the Wegovy pen at $199 a month for new patients on the first two fills of the 0.25 mg and 0.5 mg doses, then $349 a month for 0.25 through 2.4 mg, and the Wegovy pill from $149 a month, rising to $299 at the 9 mg and 25 mg strengths. Lilly lists Zepbound self-pay starting at $299 a month for the KwikPen or four vials, and the $449 price on higher doses, pen or vial, requires a refill within 45 days, otherwise it goes to $499 at 7.5 mg and $699 from 10 mg up (11). Novo’s offer runs through December 31, 2026 and it says pricing will be updated after that (10). Lilly’s page lists no end date.

Both routes need a prescription. Novo’s prices apply when it is filled through NovoCare Pharmacy or with its savings offer (10). If you have insurance, check coverage and prior authorization first, since a covered fill beats any cash price. My cash pay prices post tracks the full ladder, including Medicare and the other federal programs.

Pills as a way out

Needles and syringes are part of why some people used compounded vials in the first place, and now there are two oral choices. Wegovy tablets start at 1.5 mg daily for 30 days, then 4 mg, then 9 mg, then 25 mg (6). Foundayo starts at 0.8 mg, steps to 2.5 mg after at least 30 days, then 5.5 mg, with room to 9, 14.5, or 17.2 mg (9). The Wegovy label does include a rule for moving from the 2.4 mg injection to the 25 mg tablet. Nothing in either label covers moving from a compounded injection, so the same logic applies: start at the bottom unless there is a good reason not to (6,9). I compared the two pills in Foundayo vs. the Wegovy Pill.

For most people it comes down to two things, preference and coverage. If insurance will help pay for Foundayo or the Wegovy pill, that is probably the most important deciding factor. If the patient is paying cash, that changes the math. And if someone doesn’t like injections, a pill usually makes more sense, as long as it is affordable and it keeps them on the medication.

Gray-market sellers and “research use” vials

When a compounded supplier folds, the next search result is often worse. FDA has warned companies that sold semaglutide, tirzepatide, and related peptides falsely labeled “for research purposes” or “not for human consumption” while supplying dosing instructions to consumers. It also says it is aware of counterfeit Ozempic, and advises buying only from state-licensed pharmacies (5). A price far below the brand cash prices above is the tell. Use FDA’s BeSafeRx tools if you are unsure about a site.

The same caution covers telehealth ads. FDA’s position is that compounded drugs are not FDA-approved (3), so a site promising “the same as Wegovy” is making a claim the agency has already penalized.

If you are the patient

Do not stretch your last vial to bridge the gap, and do not mix products. Photograph the label now, write down your last dose date, and book the switching visit before you run out. Ask your prescriber which brand product fits your coverage and budget, and expect a lower starting dose than you were on.

If you are the clinician

Document the compounded product, the pharmacy, the last dose date, and your reasoning for the starting dose, since no label supports a direct conversion. Counsel on the GI risk of reinitiation (6,7). Remember that state-licensed pharmacies that are not outsourcing facilities are not required to report adverse events to FDA, so your MedWatch report may be the only one (5).

The Bottom Line

Moving from compounded semaglutide or tirzepatide to Wegovy, Zepbound, or an oral option means a new prescription and a starting dose chosen for you, because compounded doses do not convert cleanly to brand doses.

Gap length and certainty drive the choice. A short gap on a verified, well-tolerated dose can be matched. A longer gap or an uncertain vial points toward the label starting dose and a four-week-step climb. Costs for the brand products are lower than they were, and the pills give needle-averse patients a path. Avoid gray-market sellers entirely.

Sources

U.S. Food and Drug Administration. FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize (current as of April 1, 2026). https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize
U.S. Food and Drug Administration. FDA proposes to exclude semaglutide, tirzepatide, and liraglutide on 503B bulks list. April 30, 2026. https://www.fda.gov/news-events/press-announcements/fda-proposes-exclude-semaglutide-tirzepatide-and-liraglutide-503b-bulks-list
U.S. Food and Drug Administration. FDA warns 30 telehealth companies against illegal marketing of compounded GLP-1s. March 3, 2026. https://www.fda.gov/news-events/press-announcements/fda-warns-30-telehealth-companies-against-illegal-marketing-compounded-glp-1s
Lambson JE, Flegal SC, Johnson AR. Administration errors of compounded semaglutide reported to a poison control center: case series. J Am Pharm Assoc (2003). 2023;63(5):1643-1645. PMID 37392810. https://pubmed.ncbi.nlm.nih.gov/37392810/
U.S. Food and Drug Administration. FDA’s concerns with unapproved GLP-1 drugs used for weight loss (current as of October 1, 2026). https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss
Wegovy (semaglutide) injection and tablets, prescribing information (revised June 2026). DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b
Zepbound (tirzepatide) injection, prescribing information. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b
Eli Lilly Medical Information. What should a patient do if they miss a dose of Zepbound (tirzepatide)? https://medical.lilly.com/us/products/answers/what-should-a-patient-do-if-they-miss-a-dose-of-zepbound-tirzepatide-209169
Foundayo (orforglipron) tablets, prescribing information. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8ac446c5-feba-474f-a103-23facb9b5c62
Novo Nordisk. NovoCare: Wegovy savings and self-pay options. https://www.novocare.com/wegovy/savings-card.html
Eli Lilly and Company. Zepbound savings and insurance options. https://zepbound.lilly.com/savings

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What Happens If You Stop Taking a GLP-1?

On October 16, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

Somebody asks me this almost every week, usually some version of the same sentence. “How long do I have to stay on this?”

It is a fair question and it deserves a straight answer rather than a lecture. So here is what the data says happens, what I do about it, and the handful of situations where I think stopping is the right call.

Why you want to stop matters more than the fact that you want to stop

The first thing I ask is why.

The answers cluster into three groups, and they lead to three completely different conversations. Some people have hit their goal and believe they can hold it from here on their own. Some are looking at the monthly cost and doing math. And some are uneasy about taking any medication for years on end, the same way people feel about a blood pressure pill or a statin.

None of those are unreasonable. But the plan for a patient who cannot afford the drug looks nothing like the plan for a patient who is worried about what it is doing to them over a decade, and lumping them together as “wants to stop” wastes the visit.

What the evidence actually shows

The honest version is that most of the weight comes back, and it comes back faster than people expect.

The best synthesis we have is a 2026 systematic review and meta-regression in eClinicalMedicine that pooled 48 studies (1). About 60 percent of the weight lost during treatment is regained within 52 weeks of stopping. The curve is steep early, slows, and flattens out around 60 weeks, with regain plateauing near 75 percent of what was lost. Read the other direction, roughly a quarter of the loss is still there.

The individual trials tell the same story. In the STEP 1 extension, participants had lost 17.3 percent of body weight on semaglutide. A year after the drug and the lifestyle support both stopped, they had regained 11.6 percentage points, leaving a net loss of 5.6 percent, and 48 percent were still at least 5 percent below where they started (2). In SURMOUNT-4, people who came off tirzepatide regained about 14 percent over the following year while those who stayed on lost another 6.7 percent, and 82 percent of the group that stopped gave back more than a quarter of their loss (3).

Here is the part that gets left out of the headlines, and the part I care about more than the scale. The metabolic improvements unwind first. Around 70 to 80 percent of the blood pressure improvement is gone within 12 weeks of stopping. About half of the HbA1c improvement is back by 8 to 12 weeks (1). The weight takes a year to come back. The blood pressure takes three months.

That ordering is the reason I do not treat stopping as a neutral event in someone with hypertension or diabetes.

It is physiology, not a character flaw

I want to be clear about what that regain represents, because patients are brutal with themselves about it.

These drugs work on appetite signaling. Take the drug away and the signaling returns to where it was, which means hunger returns to where it was. The body defends the higher weight. Regaining is the expected biological result of removing the treatment, not evidence that somebody got lazy in month four.

I say this out loud in visits because the shame around regain is what stops people from coming back and restarting when they need to.

Most people stop anyway

Worth knowing: stopping is the norm, not the exception.

In a cohort of 125,474 adults starting these medications, 46.5 percent of those with type 2 diabetes and 64.8 percent of those without had stopped within a year (4). An analysis of 60,000 insured patients presented at ENDO 2026 found about four in ten stopped in the first year, and nearly six in ten by two years (5).

But look at what happens next in that same data. Of the people who stopped, 41.5 percent restarted within a year and 58 percent within two (5). This is not a drug people take once and abandon. It is a drug people fall off and climb back onto, usually after the weight starts coming back.

One more number, and it is the one that changed how I think about this. An integrated health system that added structured pharmacist onboarding and real follow-up got its one-year discontinuation rate down to 3.9 percent (6). Compare that to the 46 to 65 percent above. Most of the stopping in this country is not a drug problem. It is an access, cost and support problem.

What I actually do: lower the dose rather than stop

When somebody has reached a healthy weight, my preference is not to stop the medication. It is to lower the dose to the amount that holds the weight steady instead of the amount that keeps driving it down.

I will say plainly that the evidence here is thin. There are no randomized trials of tapering or maintenance dosing after weight loss, only small observational reports (7). So this is clinical judgment rather than a protocol, and I tell patients that.

What I like about it is that it answers the three concerns at once. It costs less. It involves less drug for people who are uneasy about long-term exposure. And it keeps the appetite brake partly engaged, which is the thing that actually prevents the rebound.

When the reason is cost

This is the most common real reason, and it has the most workable solutions.

First, the cash-pay programs. Eli Lilly and Novo Nordisk both sell direct now, and the prices are meaningfully better than they used to be. For a lot of patients that alone closes the gap.

Second, insurance, which is more winnable than people assume. If a patient carries a weight-related condition, and most do, there is often a path to coverage. Diabetes, prediabetes, hypertension, high cholesterol, GERD, obstructive sleep apnea. Those are not footnotes. They are the clinical justification that gets a prior authorization approved. It is worth the paperwork.

Third, switch the drug rather than abandon the class. Semaglutide instead of tirzepatide. Liraglutide instead of either. Not identical, but real.

Fourth, Medicare, and this is the part most patients have not heard. Part D still cannot pay for a drug prescribed for weight loss alone, because that exclusion sits in the statute and the 2025 attempt to reinterpret it was never finalized. What changed is the Medicare GLP-1 Bridge, which went live July 1, 2026 and runs through the end of 2027. It puts Foundayo, Wegovy and the Zepbound KwikPen at $50 a month for eligible beneficiaries (8). The Zepbound vials and single-dose pens are not in it, which is catching people out. If a patient was told no before last summer, that answer is worth getting again.

And if none of that works, we move to what is affordable. Bupropion and naltrexone as generics. Metformin. These are not equivalent to a GLP-1 and I do not pretend otherwise. They are considerably better than nothing, which is the actual alternative on the table.

Protecting muscle

If weight is going to move in either direction, I want as much of it as possible to be fat.

I target protein intake around 1.5 grams per kilogram. I want resistance training at least twice a week, and 30 minutes of aerobic activity five days a week. That applies while losing, while maintaining, and especially after stopping.

The concern worth naming is that we do not know whether regained weight comes back in the same proportions it left. If fat returns faster than muscle, somebody can land at their old weight with worse body composition than they had before treatment. The data on that is genuinely unsettled, so I am not going to overstate it. The defense is the same either way: protein and resistance training.

When I bring up the long-term question, and why not sooner

This is where I part company with a lot of advice.

I do not open with “this is a lifelong medication.” Early on, we do not yet know whether the drug will even work for this person, and plenty of patients arrive with reservations already sitting in the back of their minds. Leading with a life sentence can talk somebody out of a treatment that might have changed their health, before anyone knows if it helps.

So I raise it as we approach maintenance, when there is something real to discuss: this is working, here is what holding onto it looks like.

When I support stopping

Not every stop is a mistake. I will back the decision in a patient who becomes pregnant, who cannot tolerate the side effects, who genuinely cannot afford it after we have worked the options, or who is not able to use it safely. That last one covers skipping the lab work, taking it in ways it was not prescribed, or developing disordered eating patterns such as bingeing and purging or restricting toward anorexia. It also covers losing more weight than is healthy and not sticking to the maintenance plan.

In those situations stopping is the correct medical decision, not a failure of resolve.

Restarting

People restart. It is common, and I treat it as a normal part of the course rather than a setback.

If somebody has been off for more than about a month, we go back to introductory dosing and step up again. Restarting at the dose you left off at is how people end up with a week of nausea they did not need to have.

For clinicians

Three things worth carrying into your own visits.

Ask the why before you negotiate the how, because cost, goal attainment and long-term safety worry need different responses.

Counsel on the cardiometabolic rebound, not only the weight. Your patient with hypertension will give back most of their blood pressure improvement inside three months, which is a faster and more clinically meaningful change than the scale (1).

And treat the discontinuation statistics as a system signal rather than a patient-adherence story. A 3.9 percent one-year discontinuation rate in a supported program, against 46 to 65 percent in the broader population, tells you where the problem actually lives (4,6).

The Bottom Line

Stopping a GLP-1 means most of the weight comes back, typically around 60 percent of it within a year, with the blood pressure and blood sugar improvements unwinding much faster than that.

That is physiology rather than failure. If you have reached a healthy weight, lowering the dose is usually a better move than stopping outright. If cost is the problem, there is more room to work than most people realize, between cash-pay pricing, prior authorization based on the conditions you already have, switching agents, and the Medicare GLP-1 Bridge if you are on Medicare. And if you do stop, protect your muscle, and come back without embarrassment if the weight starts climbing. Restarting is common and it works.

Sources

Budini B, Luo S, et al. Trajectory of weight regain after cessation of GLP-1 receptor agonists: a systematic review and nonlinear meta-regression. eClinicalMedicine. 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC13043475/
Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564. https://pmc.ncbi.nlm.nih.gov/articles/PMC9542252/
Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial. JAMA Internal Medicine. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2841273
Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity. JAMA Network Open. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2829779
Endocrine Society. More than half of those who stop GLP-1s restart within a year. ENDO 2026, presented June 14, 2026. https://www.endocrine.org/news-and-advocacy/news-room/2026/sontha-press-release-endo-2026
Health System Pharmacies Keep Patients on GLP-1 Therapy. American Journal of Managed Care. https://www.ajmc.com/view/health-system-pharmacies-keep-patients-on-glp-1-therapy
Scripps. Patients Maintained Weight Loss After Reducing GLP-1 Treatment Frequency. https://www.scripps.org/news_items/8102-scripps-patients-maintained-weight-loss-after-reducing-glp-1-treatment-frequency
Medicare GLP-1 Bridge: Information for Providers. Centers for Medicare & Medicaid Services. https://www.cms.gov/medicare/coverage/prescription-drug-coverage/medicare-glp-1-bridge/information-providers

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Does Mounjaro Lower Your Risk of Heart Attack and Stroke?

On September 18, 2026September 18, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

On August 28, 2026, the FDA approved a new use for Mounjaro (tirzepatide): lowering the risk of cardiovascular death, nonfatal heart attack, and nonfatal stroke in adults with type 2 diabetes who are at high risk for those events (1). That is a real change written into the drug’s FDA-approved label. The short version is this: tirzepatide matched, but did not beat, a diabetes drug that already had proven heart benefits of its own. Whether that counts as exciting news depends on what you were expecting going in.

What the Label Now Says

Mounjaro’s original approval covered blood sugar control in adults, later extended to children age 10 and up with type 2 diabetes in December 2025 (3). The new cardiovascular indication sits on top of that one. It reads, in the FDA’s language, as lowering the risk of major adverse cardiovascular events, meaning cardiovascular death, nonfatal heart attack, or nonfatal stroke, in adults with type 2 diabetes who are already at high risk for those events (1, 2). That population matters: this approval is specific to people with type 2 diabetes who already carry meaningful cardiovascular risk, largely established atherosclerotic disease.

An outcomes indication like this one is a different category of claim than glycemic control. It says the drug changed what happens to a person’s heart and vessels over years, something a lab value at three months cannot tell you on its own. That distinction is the entire reason a cardiovascular outcomes trial exists.

The Trial Behind It

The approval rests on SURPASS-CVOT, a randomized, double-blind trial that enrolled more than 13,000 adults with type 2 diabetes and established atherosclerotic cardiovascular disease across 640 sites in 30 countries (4). Participants were assigned to tirzepatide, titrated up to 15 mg weekly or their highest tolerated dose, or dulaglutide (Trulicity) 1.5 mg weekly, followed for a median of roughly four years. Dulaglutide was not a placebo. A drug with its own proven cardiovascular track record from the REWIND trial, chosen deliberately as a harder comparator than sugar water.

The primary outcome, a composite of cardiovascular death, heart attack, or stroke known as three-point MACE, occurred in 12.2 percent of the tirzepatide group and 13.1 percent of the dulaglutide group. That is a hazard ratio of 0.92, with a 95.3 percent confidence interval of 0.83 to 1.01 (4). Tirzepatide met the prespecified bar for noninferiority (p=0.003). It did not meet the bar for superiority (p=0.09). Read plainly: tirzepatide did not fall behind a drug already known to protect the heart, and it numerically edged ahead, but the trial cannot say with statistical confidence that it beat dulaglutide on this endpoint.

Two other numbers are worth knowing even though they sit outside the approved claim. All-cause mortality was 16 percent lower with tirzepatide than with dulaglutide, hazard ratio 0.84, 95 percent confidence interval 0.75 to 0.94, per Lilly’s topline results release (5). And the weight difference was large: about 11.6 percent body weight reduction with tirzepatide against 4.5 percent with dulaglutide (4), which tracks with everything already known about how the two drugs differ on that front. Neither of those numbers was the tested primary endpoint, so treat them as suggestive rather than proven.

I do not read this trial as evidence that tirzepatide is the better heart drug. I read it as evidence that choosing tirzepatide over an active cardioprotective comparator costs you nothing on the cardiovascular side, while it still outperforms on weight and blood sugar. That is a useful thing to know, and it is a smaller claim than the headlines will make it sound.

Where This Leaves Ozempic, Wegovy, and Zepbound

Semaglutide already has cardiovascular outcomes data of its own, built from different comparators and different populations, which matters when you start comparing hazard ratios across trials. SUSTAIN-6 tested injectable Ozempic against placebo in type 2 diabetes at high cardiovascular risk and found a hazard ratio of 0.74 (6). Ozempic tablets, oral semaglutide, picked up their own cardiovascular indication in October 2025 based on the SOUL trial, hazard ratio 0.86, in a population with type 2 diabetes and atherosclerotic disease, chronic kidney disease, or both, broader than “established cardiovascular disease” alone (7). Wegovy’s SELECT trial went further still: adults with overweight or obesity and established cardiovascular disease, no diabetes required at all, hazard ratio 0.80 against placebo (8).

Four trials went into these numbers, each built around its own comparator and its own patient population. Lining the hazard ratios up side by side and picking a winner overstates what any single number can tell you. SURPASS-CVOT is the only one of the four tested against an active drug with its own proven benefit, a harder bar to clear even when the resulting number looks smaller.

Zepbound carries no such indication yet. Zepbound and Mounjaro are the same molecule, tirzepatide, at the same doses. The difference is entirely regulatory. Mounjaro is approved for type 2 diabetes, and its new cardiovascular claim comes from a trial that specifically enrolled people with diabetes. Zepbound is approved for obesity and, separately, moderate to severe obstructive sleep apnea. Its own cardiovascular outcomes trial, SURMOUNT-MMO, is still enrolling, expected to include roughly 15,000 adults with obesity who do not have diabetes, and has not reported results (9). Tirzepatide’s heart benefit currently exists on the books only under the Mounjaro name, for a population that has diabetes.

For Patients

If you have type 2 diabetes and known heart disease and you are already doing well on dulaglutide, this trial should reassure you. Superiority was not shown, so nothing in the data requires a change if your current regimen is working. If your blood sugar or weight has been harder to manage, this approval gives your clinician a documented, FDA-recognized reason to discuss tirzepatide.

Coverage is worth asking about directly. An outcomes-based indication sometimes changes how an insurer’s prior authorization process treats a drug, because it can be framed as reducing a documented risk of death rather than only managing a lab value. That is not guaranteed, and formularies vary by plan. Ask specifically whether this new indication affects your prior authorization, rather than assuming it automatically will.

Patients on my video visits do ask about switching from semaglutide to tirzepatide after news like this. I tell them to stay on semaglutide if it’s working. Superiority was not shown here, so a regimen that is already working has no data forcing a change.

The Practical Question for Prescribers

For a patient with type 2 diabetes and established cardiovascular disease, tirzepatide’s larger effect on weight and A1c, paired with a trial showing it keeps pace on cardiovascular safety against an already-protective drug, makes a reasonable case for choosing it first. That is my opinion, and it deserves the caveat the superiority test earned: the point estimate favored tirzepatide, but the confidence interval did not exclude the possibility of no difference at all.

The active-comparator design is also worth sitting with. Because there was no placebo arm, SURPASS-CVOT cannot independently quantify tirzepatide’s benefit against doing nothing. It borrows dulaglutide’s REWIND-established benefit and shows tirzepatide keeps that benefit intact. Proving a brand new benefit from scratch would have required a placebo arm, and this trial did not have one.

When type 2 diabetes is the indication, I prescribe Mounjaro.

The Bottom Line

Tirzepatide gives up nothing on heart safety when measured against a drug that already protects the heart, and it does more for weight and A1c along the way. That is the real result of SURPASS-CVOT, even though the trial stopped short of proving superiority: the noninferiority bar was met (p=0.003), the superiority bar was not (p=0.09). If you have type 2 diabetes and heart disease, ask your prescriber whether tirzepatide fits your regimen better than what you are on now, and ask whether this new indication changes what your insurer will approve. The August 28, 2026 approval gives that conversation a documented reason to happen (1).

Sources

1. FDA approves Lilly’s Mounjaro (tirzepatide) to reduce cardiovascular risk in adults with type 2 diabetes. Eli Lilly and Company, August 28, 2026. https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-mounjaro-tirzepatide-reduce-cardiovascular

2. FDA Expands Tirzepatide Label to Reduce Cardiovascular Risk in Type 2 Diabetes. AJMC. https://www.ajmc.com/view/fda-expands-tirzepatide-label-to-reduce-cardiovascular-risk-in-t2d

3. FDA approval letter, supplement 215866/S-039 (pediatric type 2 diabetes indication, age 10 and older). U.S. Food and Drug Administration, December 19, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/215866Orig1s039ltr.pdf

4. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes (SURPASS-CVOT). New England Journal of Medicine, December 2025. PMID 41406444. https://pubmed.ncbi.nlm.nih.gov/41406444/

5. Lilly’s Mounjaro (tirzepatide), a GIP/GLP-1 dual agonist, demonstrated cardiovascular protection in landmark head-to-head trial. Eli Lilly and Company, July 31, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-mounjaro-tirzepatide-gipglp-1-dual-agonist-demonstrated

6. Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6). N Engl J Med. 2016;375:1834-1844. https://www.nejm.org/doi/full/10.1056/NEJMoa1607141

7. McGuire DK, Marx N, Mulvagh SL, et al. Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes (SOUL). N Engl J Med. 2025. https://www.nejm.org/doi/full/10.1056/NEJMoa2501006

8. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023;389:2221-2232. PMID 37952131. https://pubmed.ncbi.nlm.nih.gov/37952131/

9. Tirzepatide for Reduction of Morbidity and Mortality in Adults with Obesity (SURMOUNT-MMO). ClinicalTrials.gov, NCT05556512. https://clinicaltrials.gov/study/NCT05556512

A wooden table in warm morning light with a coiled cloth tape measure, a small hand weight and a folded linen cloth

Does Menopause Cause Weight Gain, or Is It Just Aging?

On August 29, 2026September 11, 2026 By Dr. Scott RennieIn Menopause & Women's Health, Weight Loss & Metabolic HealthLeave a comment

Your weight has been climbing about a pound a year since your early forties. Then something else changed. Same body, rearranged. The jeans that caught at the hip now catch at the waist.

Aging put the weight on. Menopause moved it.

The scale was never the menopause story

The Study of Women’s Health Across the Nation tracked women through the transition with repeated DXA scans. Weight and BMI gains that begin in premenopause “continue on an unaltered trajectory” through it, then flatten after the final period (1). Menopause does not bend the weight curve. The curve was already bending.

Two SWAN numbers circulate and both are real. In the full cohort of 3,064 women aged 42 to 52, weight rose 2.1 kg over three years, about 0.7 kg a year (2). In the smaller DXA sub-cohort, inside the 3.5-year window around the final period, 0.25 kg a year (1). Call it a pound to a pound and a half a year through midlife, none of it accelerated by menopause.

Where the fat goes

In 380 SWAN women with serial DXA, visceral fat drifted down before the transition at 1.85% a year, then climbed 6.24% a year inside the transition window (95% CI 4.31 to 8.17), settling at 1.47% after (3). Android fat went from 1.21% to 5.54%; the hip and thigh depot only to 2.03%. Lean mass flips sign in the same window, from gaining 0.2% a year to losing 0.2% (1), on top of the 3% to 8% per decade women lose after 30 (4).

Waist girth, meanwhile, rises 0.55% a year before the transition and 0.96% during it (3). Visceral fat moves six times faster than the tape can see, which is why a stable BMI and an unchanged waist are not reassurance.

Your metabolism did not crash at 50

Doubly labeled water, the reference method for what a human actually burns, was applied to 6,421 people across 29 countries. Total expenditure, basal expenditure and fat-free mass were “all stable from age 20 to 60” (5). The break point for adjusted total expenditure sits at 63.0 years, and the decline after it runs 0.7% a year (5).

The estradiol-specific effect is real and modest. Forty-five premenopausal women were randomized to ovarian suppression with placebo or transdermal estradiol add-back. Resting expenditure fell 54 kcal a day on placebo and did not fall at all with estradiol (6). Fifty-four calories. Measurable. Not a collapse.

Why it happens, and how much of that is known

Less than the confidence of the explanations would suggest. Estradiol loss lowers resting expenditure, since add-back prevented it in a randomized design (6), and the redistribution is time-locked to the final period rather than to birthdays (3). Past that it thins out fast. The one randomized ovarian-suppression trial measuring body composition and free-living expenditure together, 34 women over 24 weeks, found no endpoint that differed between groups (7). The Menopause Society says estrogen regulation of energy intake and expenditure “has not been well studied,” with “a paucity of studies” on estrogen and skeletal muscle (8). Falling estradiol, rising FSH, the androgen-to-estrogen shift: nobody has sorted out which drives it.

What shows up on your labs

SWAN modeled cardiovascular risk factors two ways in 1,054 women with a natural final period, once as chronological aging and once as ovarian aging. Only total cholesterol, LDL cholesterol and apolipoprotein B jumped inside the year before and after the final period (9). Glucose, insulin, blood pressure, fibrinogen and CRP fit the plain aging model (9), and the American Heart Association agrees (10).

So insulin resistance is not independently menopause-driven, whatever you have been told. The visceral fat is menopause-linked, and visceral fat drives insulin resistance on its own. A chain, not a shortcut, and it points at different treatment.

Here is where my own practice diverges from the cohort data. I screen lipids and apoB at intake, before starting any medication for weight loss, so my trigger is the visit rather than the menopausal stage. For hormone therapy I don’t routinely order them. I give the patient the options and tell her up front that insurance sometimes will not pay for apoB or apoA testing, which turns out to be a real constraint on what actually gets drawn.

Lift something heavy, then eat enough protein to use it

101 randomized trials, 5,697 postmenopausal women. Training raised fat-free mass 0.66 kg and cut fat mass 1.27 kg, and the modalities split: resistance work won for lean mass (+0.90 kg), aerobic for fat and waist (1.94 kg, 2.30 cm) (11).

Protein partners that work rather than replacing it. In 776 postmenopausal women aged 55 and older, whey improved lower-limb lean mass and strength when paired with resistance training, and had “no significant benefit on muscle strength or lean mass” without it (12). The powder is not the intervention.

Write down 1.2 g of protein per kilogram daily, 150 minutes of moderate activity weekly, strength training twice a week (4). On an incretin, higher: 1.2 to 1.6 g/kg/d, strength work three times weekly (13).

The strongest diet trial here is a prevention trial

The Women’s Healthy Lifestyle Project randomized 535 premenopausal women, mean age 47, and followed them 54 months through the transition. The intervention group finished 0.2 lb lighter. Controls gained 5.2 lb (14). Which diet matters less: 144 centrally obese postmenopausal women randomized to an energy-restricted Mediterranean or Central European diet both lost 7.6 kg and 24.6% of visceral fat in 16 weeks, with no difference between arms (15). Choose the one you will still be doing next year.

Hormone therapy, stated precisely in both directions

A Cochrane review of 28 randomized trials and 28,559 women found no evidence that estrogen alone or estrogen with progestogen affects body weight or prevents the BMI increase normally experienced at menopause (16). That review is old, last published in 2000, and still the largest pooled analysis of that endpoint. Hormone therapy does not cause weight loss, and it does not prevent menopausal weight gain.

What it does is narrower. The Menopause Society’s own key point: hormone therapy “may help attenuate abdominal adipose accumulation and weight gain associated with the menopause transition,” and “the effect is small” (8). In the WHI, no significant slowing of weight gain and a lesser waist increase over three years (8). On muscle, systematic reviews find neither benefit nor harm (8). A 2026 review is blunt: hormone therapy “should not be marketed or prescribed for weight loss or obesity treatment” (17).

Good drug. Vasomotor symptoms, genitourinary syndrome, bone. Abdominal fat is not on that list.

My own practice, stated plainly: I don’t prescribe MHT for patients who want to lose abdominal fat.

GLP-1s and the muscle question

Menopausal status does not blunt these drugs. A post hoc SURMOUNT analysis by reproductive stage found tirzepatide produced 23% weight reduction in postmenopausal women against 3% on placebo, matching premenopausal women at 26% versus 2% (18).

Now the counterintuitive part. In the SURMOUNT-1 DXA substudy, 160 participants scanned at baseline and week 72, tirzepatide produced 21.3% weight loss, 33.9% fat mass loss and 10.9% lean mass loss (19). Of the weight lost, roughly 75% was fat and 25% lean in both the tirzepatide and the placebo arms (19). The lean loss scales with the weight lost rather than with the drug.

DXA lean mass is also not muscle. It counts water, glycogen and organ mass, and modeling puts true muscle loss nearer 10% to 15% of weight reduction in women who are not strength training (13). In a 106-patient semaglutide cohort, grip strength rose 4.1 kg at a year and sarcopenic obesity fell from 49% to 33% (20). Function can improve while the DXA number falls.

Still, nobody has published incident sarcopenia or functional outcomes for postmenopausal women on these drugs. That gap is why protein and lifting belong in the prescription.

When I start a postmenopausal patient on an incretin, the instruction is 1.6 g of protein per kilogram of body weight a day, and strength training two to three times a week. That is the top of the range the evidence supports (13), and I put it there on purpose.

What is oversold

Supplements sold for menopausal weight loss. I looked for a randomized trial of any of them showing meaningful weight or visceral fat reduction and found none. Absence of evidence in one search is not proof of absence, so put it precisely: the marketing category exists; the trial literature does not. The Menopause Society does not recommend supplements or herbal remedies even for hot flashes (21).

Hormone therapy stacked on a GLP-1. Two retrospective cohorts, no randomized trial, and the 2026 review is unambiguous: do not start hormone therapy to boost an obesity medication (17).

And one asymmetry worth getting exactly right. Treating hot flashes or insomnia in order to lose weight has no trial behind it that I can find. The reverse direction is supported: the Menopause Society recommends weight loss for vasomotor symptoms, conceding those studies are small pilots and post hoc analyses (21).

If you are the patient reading this

Stop asking whether menopause made you gain weight. Ask where it went. Your BMI can sit still while visceral fat climbs 6% a year (3), so get lipids and apoB checked around your final period (9). Then put your effort where the randomized evidence is: resistance training, and a deficit you can hold for years.

Which raises the obvious question for a practice that runs entirely over video. So here is what I actually do. Patients get a Withings scale that syncs into the chart on its own and reports weight, BMI and body fat. A blood pressure cuff syncs the same way, automatically. The waist they measure themselves, with a tape, because the scale will not catch what the tape catches. Weight and blood pressure come in at least monthly and often more frequently than that, which means the trend is visible long before an annual visit would have found it.

For the clinicians

Screening beats explaining. The window runs roughly two years before to 18 months after the final period (1), and that is when lipids move and visceral fat accelerates (3)(9). Order the panel with apoB in it, and do not reassure a woman on a stable BMI or an unchanged waist; both understate a 6.24% per year visceral gain (3). When you start an incretin, write the protein target and the strength training into the plan (13). Hormone therapy earns its place on symptoms, bone and the diabetes signal (8), and no line at all on the weight plan.

The Bottom Line

Aging adds the weight, roughly a pound and a half a year through midlife, on a curve menopause does not bend (1)(2). Menopause moves the fat, visceral gain going from minus 1.85% to plus 6.24% a year inside a 3.5-year window (3). Metabolism holds steady to 60 (5). Hormone therapy treats symptoms and bone, not weight (8)(16). What changes the outcome is lifting, protein, a deficit you can sustain, and where indicated, a medication that works as well after menopause as before (11)(18).

Sources

1. Greendale GA, et al. Changes in body composition and weight during the menopause transition. JCI Insight 2019. https://pmc.ncbi.nlm.nih.gov/articles/PMC6483504/

2. Sternfeld B, et al. Physical activity and changes in weight and waist circumference in midlife women. Am J Epidemiol 2004. https://academic.oup.com/aje/article/160/9/912/86561

3. Greendale GA, et al. Changes in regional fat distribution and anthropometric measures. J Clin Endocrinol Metab 2021. https://pmc.ncbi.nlm.nih.gov/articles/PMC8372653/

4. The Menopause Society. MenoNote: Midlife Weight Gain, 2025. https://menopause.org/wp-content/uploads/for-women/MenoNote-Weight-Gain.pdf

5. Pontzer H, et al. Daily energy expenditure through the human life course. Science 2021. https://doi.org/10.1126/science.abe5017

6. Melanson EL, et al. Regulation of energy expenditure by estradiol in premenopausal women. J Appl Physiol 2015. https://pmc.ncbi.nlm.nih.gov/articles/PMC4628992/

7. Gavin KM, et al. Ovarian suppression in premenopausal women: no change in free-living energy expenditure. Obesity 2020. https://pmc.ncbi.nlm.nih.gov/articles/PMC7653843/

8. North American Menopause Society. 2022 hormone therapy position statement. Menopause 2022. https://menopause.org/wp-content/uploads/professional/nams-2022-hormone-therapy-position-statement.pdf

9. Matthews KA, et al. Chronological aging or the menopausal transition? J Am Coll Cardiol 2009. https://doi.org/10.1016/j.jacc.2009.10.009

10. El Khoudary SR, et al. Menopause transition and cardiovascular disease risk. Circulation 2020. https://doi.org/10.1161/CIR.0000000000000912

11. Khalafi M, et al. Exercise training and body composition in postmenopausal women. Front Endocrinol 2023. https://pmc.ncbi.nlm.nih.gov/articles/PMC10306117/

12. Kuo YY, et al. Whey protein supplementation in postmenopausal women. Nutrients 2022. https://pmc.ncbi.nlm.nih.gov/articles/PMC9572824/

13. Mozaffarian D, et al. Nutritional priorities to support GLP-1 therapy for obesity. Am J Clin Nutr 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC12612741/

14. Kuller LH, et al. Women’s Healthy Lifestyle Project: results at 54 months. Circulation 2001. https://doi.org/10.1161/01.cir.103.1.32

15. Bajerska J, et al. Energy-restricted Mediterranean and Central-European diets in postmenopausal women. Sci Rep 2018. https://pmc.ncbi.nlm.nih.gov/articles/PMC6057942/

16. Kongnyuy EJ, et al. Hormone replacement therapy: weight and body fat distribution. Cochrane Database Syst Rev CD001018. https://www.cochrane.org/evidence/CD001018_hormone-replacement-therapy-has-no-effect-body-weight-and-cannot-prevent-weight-gain-menopause

17. Younglove C. Menopause hormone therapy in weight management. Obesity Pillars 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC13010941/

18. Tchang BG, et al. Weight reduction with tirzepatide by reproductive stage: SURMOUNT post hoc analysis. Obesity 2025. https://doi.org/10.1002/oby.24254

19. Look M, et al. Body composition changes with tirzepatide in SURMOUNT-1. Diabetes Obes Metab 2025. https://doi.org/10.1111/dom.16275

20. Alissou M, et al. Semaglutide, fat mass, lean mass and muscle function: SEMALEAN. Diabetes Obes Metab 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC12673431/

21. North American Menopause Society. 2023 nonhormone therapy position statement. Menopause 2023. https://menopause.org/wp-content/uploads/professional/2023-nonhormone-therapy-position-statement.pdf

A bowl of Greek yogurt with blueberries, two brown eggs and a glass of water on a wooden table in morning window light

Do Ozempic and Zepbound Cause Muscle Loss?

On August 8, 2026September 11, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

Every few months a new worry about GLP-1 therapy moves through the news cycle. Lately the one I’m fielding most on video visits is muscle. Patients read a headline about “Ozempic muscle” or see a segment warning that these drugs are quietly turning people frail, and they show up to their visit asking whether the weight they’re losing is actually fat, or whether they’re hollowing out their strength along with it. Most just phrase it in terms of what they saw online: GLP or Ozempic muscle loss. Truth is, most of my patients aren’t that worried about it at first. They’re focused on getting the fat off. But some have seen the scare ads on Facebook and other social media railing against GLP-1 medications in general, touting muscle loss as the reason to avoid them. It’s a fair question, and it deserves a real answer.

What the data actually shows

Here’s the uncomfortable part first: the concern isn’t manufactured. Across GLP-1 and dual-agonist trials, roughly 25 to 40 percent of total weight lost is lean mass rather than fat mass, and that share climbs with higher doses and greater total weight loss. In patients losing more than 15 percent of body weight on high-dose therapy, average lean mass decline runs in the range of 10 to 15 percent. That’s not trivial, and it’s higher than what we’d want to see if the sole measuring stick were “weight coming off.”

Lean mass loss and clinically meaningful muscle loss aren’t the same thing, though, and this is where I think the public conversation gets sloppy. Lean mass includes water, organ tissue, and connective tissue alongside contractile muscle. Some degree of lean mass loss happens with any significant weight reduction, including bariatric surgery and aggressive caloric restriction without any medication at all. The relevant clinical question is whether strength and function held up, and whether frailty risk moved. On that narrower and more important question, the current evidence is reassuring for most patients: there’s no consistent signal that GLP-1-induced weight loss causes outright sarcopenia or functional decline in the general obesity population studied so far.

Where the concern sharpens is in specific subgroups: adults over 65, patients with baseline sarcopenia or frailty, and anyone starting from a lower muscle reserve. That’s the population where I’m paying closer attention now, more than the healthy 40-year-old with obesity and good baseline strength.

What’s changing in how we prescribe

A few practical shifts have made their way into how I approach this with patients this year. When muscle preservation is a priority, I start low and titrate slower. This isn’t new advice for tolerability, but it applies here too: aggressive, fast weight loss appears to pull proportionally more from lean mass than a slower trajectory toward the same endpoint.

Protein intake is no longer an aside I mention on the way out the door. Current guidance points to 1.2 to 1.6 g/kg of body weight per day for patients on GLP-1 therapy, meaningfully higher than general population recommendations, and given how much these medications suppress appetite, hitting that number takes real intention. I’ve started asking patients to walk me through a typical day’s protein intake rather than assuming they’re getting enough just because they’re eating less overall.

Resistance training is now part of the treatment plan itself, prescribed with the same specificity as the medication. Two or more sessions a week of resistance work is the most consistent lever we have for preserving lean mass during GLP-1-driven weight loss. For patients who’ve never lifted weights, even bodyweight or band-based resistance work at home is a reasonable starting point, and it’s worth a specific referral to physical therapy or a trainer rather than a general nudge.

And I’m tracking more than the scale. For patients on higher doses, losing significant weight, or starting from a place of reduced muscle reserve, I’m now discussing body composition tracking, whether that’s a DEXA scan, bioelectrical impedance, or simply following functional measures like grip strength and chair-stand time, rather than relying on weight alone to judge how treatment is going. I’ll say plainly: I don’t yet fully trust the consumer-grade body composition numbers patients bring me on their phones. Grip strength and chair-stand time are the measures I put the most weight on. Over video I’m relying on what a patient can demonstrate on camera and tell me, rather than testing it myself, which is a real limitation of doing this work remotely.

Muscle is not the only tissue worth watching on these drugs. Nerve complaints turn up too, from skin that hurts to the touch through to the more serious neuropathies, and the risk of both rises with dose and with how fast the weight comes off. I cover that separately in GLP-1 skin and nerve pain.

What’s coming that may change this conversation further

Drug development is moving on this too, well past prescribing technique. At the American Diabetes Association’s 85th Scientific Sessions this year, early data from the BELIEVE study looked at bimagrumab, an antibody that blocks activin receptor signaling, paired with semaglutide, specifically to see whether it could preserve lean mass during GLP-1 weight loss without blunting fat loss. Separately, researchers at Stanford published mouse data in June showing that a muscle-repair-targeted compound improved muscle regeneration and strength recovery alongside GLP-1 treatment, again without compromising fat loss. Neither approach is available for patients today, but they reflect where the field is heading: toward combination approaches that decouple fat loss from lean mass loss more deliberately.

Where the newer agents in the pipeline land on this question is also worth watching. Retatrutide, the triple GIP/GLP-1/glucagon agonist from Lilly, posted strong topline results across its TRIUMPH program this year, with weight loss in the 20 to 28 percent range depending on the trial population, and a BLA submission is planned for early 2027. Amgen’s MariTide, a monthly injectable combining a GLP-1 agonist with an amylin antibody, showed roughly 20 percent weight loss in Phase 2 with a safety profile consistent with the existing GLP-1 class. Body composition data from both programs will matter as much as the topline weight-loss numbers once they mature.

The bottom line

Muscle loss with GLP-1 therapy is real, but it’s manageable, not a reason to avoid treatment or panic mid-course. Older adults and anyone with baseline frailty need the closest attention, and so does anyone pursuing rapid, high-percentage weight loss on a higher dose. I order a DEXA when I actually need an answer to how much of that weight is fat, and it’s an easier call in a patient who might also have osteoporosis, since the same scan answers both questions. Insurance makes this harder than it should be, and plenty of patients who already know they’re overweight don’t want to pay out of pocket just to confirm it. Protein intake and resistance training aren’t optional add-ons anymore. They’re as much a part of the standard prescription as the injection itself.

Wegovy 7.2 mg: Who Should Consider the Higher Dose?

On July 31, 2026September 11, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

Wegovy just got a new top rung on the ladder. In March of this year, the FDA approved a higher, 7.2 mg dose of semaglutide, marketed as Wegovy HD, for adults with obesity or overweight. This is a new ceiling on a drug we already know well. Same drug. Higher rung. I think it’s worth walking through what the data actually shows before deciding who in your practice, or mine, is a good candidate for it.

The approval leaned on two trials, STEP UP and STEP UP T2D, both 72-week phase 3 studies. In STEP UP, which enrolled adults with obesity but without type 2 diabetes, patients on 7.2 mg lost an average of 20.7% of body weight, compared with 15.6% on the standard 2.4 mg dose and 3.9% on placebo, a meaningful jump and not a marginal one. Almost a third of patients on the higher dose, 31.2%, lost a quarter or more of their starting body weight. In the companion trial, STEP UP T2D, which looked at patients with obesity and type 2 diabetes, the numbers were lower but still substantial: 14.1% average weight loss, with about a fifth of patients losing 20% or more. That gap between the diabetes and non-diabetes cohorts isn’t surprising. We see it consistently with GLP-1 therapy, and it’s a good reminder to set expectations differently for patients with T2D up front.

Here’s the part that matters most for how I’ll actually use this in practice: Wegovy HD isn’t a starting dose. The label requires that a patient have already tolerated 2.4 mg for at least four weeks before stepping up, and the escalation is meant for patients where additional weight loss is clinically indicated, meaning the 2.4 mg dose hasn’t gotten them where they need to be. So the ideal candidate is someone who’s already on semaglutide, tolerating it reasonably well, but has plateaued short of their goal or still has a lot of excess weight to lose relative to their comorbidities. Think of a patient who’s been on 2.4 mg for six months, lost maybe 10-12% of body weight, tolerates the GI side effects fine, but still has a BMI well into obesity range with sleep apnea or hypertension that hasn’t fully responded. That’s the kind of case where I’d bring up 7.2 mg. It’s not for someone just starting therapy, and it’s not for someone who’s struggling with nausea or GI symptoms at the lower dose. If they can’t tolerate 2.4 mg, going higher solves nothing.

Which brings up the safety side, because the tradeoff here is real.

Overall tolerability at the higher dose was described as similar to what’s been seen with 2.4 mg, with GI effects like nausea, vomiting, constipation, and abdominal pain remaining the most common complaints. But two numbers stood out to me. Dysesthesia, essentially altered or abnormal skin sensation, occurred in 22% of patients on 7.2 mg versus 6% on 2.4 mg and 0.3% on placebo. That’s not a side effect I’d been counting on discussing much with patients on standard-dose semaglutide, and it’s one I’ll need to specifically ask about at follow-up visits once patients move up. I’ve seen the same pattern in my own patients, the ones who dose escalate quickly on standard Wegovy dosing, well before anyone gets near 7.2 mg. The trial data and my own visit notes agree on that one. Dose reductions due to adverse events were also more common at the higher dose, 18.5% versus 12.4% on 2.4 mg, and discontinuation due to side effects ran around 5.4%. The higher dose isn’t a free upgrade. You’re trading tolerability for more weight loss, and that’s a conversation to have explicitly with the patient rather than assume they’d automatically want the escalation.

From a practical standpoint, Wegovy HD is expected to be available through pharmacies and telehealth channels starting in April, delivered in a single-dose pen. I don’t think this changes how I approach a new patient starting on semaglutide at all, the same titration principles from 2.4 mg still apply. What it does is give me another option for the subset of patients who’ve done well but not well enough, and who’ve shown they can handle the medication without major GI intolerance. That’s a narrower group than “everyone on Wegovy,” and I’d resist the urge, mine or a patient’s, to jump to the higher dose just because it’s now available. The data supports it for the right patient. It doesn’t support treating it as the new default starting point.

Scott Rennie, D.O.
Board Certified in Obesity Medicine and Family Medicine

This blog is for educational purposes only and does not constitute individual medical advice. Always consult your own physician before making changes to your health, medications, or treatment plan.

Sources:

FDA approves high-dose Wegovy 7.2 mg for adults with obesity, Healio: https://www.healio.com/news/endocrinology/20260319/fda-approves-highdose-wegovy-72-mg-for-adults-with-obesity

FDA approves Novo Nordisk’s new Wegovy HD injection, delivering the highest weight loss to date for a Wegovy injection, PR Newswire: https://www.prnewswire.com/news-releases/fda-approves-novo-nordisks-new-wegovy-hd-injection-delivering-the-highest-weight-loss-to-date-for-a-wegovy-injection-adding-to-its-already-expansive-clinical-profile-302718982.html

STEP UP Trial Shows Higher Dose of Wegovy Produces Significant Weight Loss in Adults With Obesity Without Diabetes, Applied Clinical Trials Online: https://www.appliedclinicaltrialsonline.com/view/wegovy-weight-loss-obesity-diabetes

Digital scale showing weight comparison of green and purple capsules in milligrams

Foundayo vs. the Wegovy Pill: Comparing the Two New Weight Loss Pills

On July 31, 2026November 7, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

For years, if you asked me “is there a pill version of these weight-loss drugs?”, the honest answer was no, not really. That changed twice, four months apart. If you haven’t been following closely, the options today look nothing like they did two years ago.

A quick note on names first, since patients ask me this a lot. The Lilly drug some people have heard called “Fonday-o” is orforglipron. The FDA approved it on April 1, 2026, under the brand name Foundayo (1). Before that, on December 22, 2025, the FDA approved a 25 mg oral semaglutide tablet under the Wegovy name (2). GLP-1 medicines help control appetite and blood sugar, and that tablet was the first pill version of one approved for long-term weight management. Both are real, both are approved, and both can be prescribed today.

Both full prescribing labels are now public, and they differ in ways that decide the choice for a lot of people. Most of those differences have nothing to do with how much weight each one takes off.

Why the two pills work so differently in your body

Semaglutide is a peptide, which is a small chain of amino acids, the building blocks of proteins. Your stomach is very good at breaking down peptides, which is exactly why semaglutide originally had to be given as a shot.

Novo Nordisk’s solution was to add an ingredient called SNAC that helps the drug get absorbed before your stomach destroys it. According to a review in the journal Clinical Diabetes, SNAC does three things at once (3). It changes the local acidity around the tablet as it dissolves, it briefly protects the drug from a stomach enzyme called pepsin, and it helps the drug cross the stomach lining into your bloodstream. The absorption happens in the stomach itself rather than the intestines, which is unusual for a pill. The drug essentially enters your body right where the tablet is sitting against your stomach wall.

That trick comes with a catch, and the label is specific about it (4). You take the tablet on an empty stomach in the morning with no more than four ounces of plain water. No other liquids. Swallow it whole, and wait at least 30 minutes before you eat, drink anything, or take any other oral medication.

Thirty minutes. Every morning. Before coffee.

Orforglipron works completely differently. It is a small molecule, meaning a stable chemical rather than a fragile peptide chain. It belongs to the same drug family, mimicking a natural gut hormone that reduces appetite, but with no peptide to protect it needs no absorption booster and carries no timing ritual. Its label says to take it once daily with or without food, and specifies no water restriction and no waiting period (5). For someone who works nights, or who already swallows six other pills at breakfast, that is the whole ballgame.

What the labels actually say, and why the number in your news feed is wrong

Most of the figures circulating online come from journal publications and press releases rather than from the approved labels. The label numbers are the ones your prescription is based on, so those are the ones I use.

For Wegovy tablets, the label reports a 64-week trial in 205 adults on the tablet against 102 on placebo, all with obesity or overweight plus a weight-related condition, with diabetes excluded (4). Average weight change was 13.6 percent down on the tablet and 2.4 percent down on placebo, a difference of 11.2 percentage points. Broken out by how much people lost: 76.3 percent lost at least 5 percent of their body weight versus 31.3 percent on placebo, 59.8 percent lost at least 10 percent versus 14.4 percent, 47 percent lost at least 15 percent versus 5.5 percent, and 27.9 percent lost at least 20 percent versus 3.1 percent.

For Foundayo, the label reports a 72-week trial in 3,127 adults without diabetes (5). Average weight change was 7.4 percent down at the 5.5 mg dose, 8.3 percent down at 9 mg, and 11.1 percent down at the maximum 17.2 mg dose, against 2.1 percent down on placebo. At 17.2 mg, 35.9 percent of patients lost at least 15 percent of their body weight, compared with 6 percent on placebo.

Put those side by side and the semaglutide tablet looks better, and I would be careful with that read. Different patients, different trial lengths, different placebo responses, and nobody randomized the same people to both. What is harder to wave away is the size of each evidence base. The semaglutide tablet’s label efficacy rests on 205 treated patients. Foundayo’s rests on 3,127. Both cleared the FDA, so both met the bar, but I have more confidence in how a drug behaves across a wide range of real people when the number in the trial is measured in thousands.

Here is the detail that confuses almost everyone who reads the news coverage. The approved Foundayo strengths are 0.8, 2.5, 5.5, 9, 14.5, and 17.2 mg, stepped up roughly every 30 days. The trial used a capsule at 1, 3, 6, 12, 24, and 36 mg. Those map onto each other in order, so the 17.2 mg tablet you can actually be prescribed is the 36 mg dose you read about. If your maximum dose sounds far smaller than the headline, that is why.

One thing I noticed reading the Foundayo label closely: the 14.5 mg strength is approved and dispensable, and it does not appear in the label’s efficacy table at all. You can be prescribed a dose with no published average weight loss attached to it. Not dangerous, just worth knowing if you end up parked there.

The only comparison anyone has run, and who paid for it

There is still no head-to-head trial of these two drugs in obesity. There is now an indirect comparison, published in Diabetes, Obesity and Metabolism in August 2026, which pulled individual patient data from the semaglutide tablet trial and aggregate data from the orforglipron trial and statistically adjusted for differences in sex, body weight and glucose status between the two populations (6).

It found oral semaglutide 25 mg ahead by 3.2 percentage points of body weight (95% confidence interval 5.9 to 0.4) and reported higher discontinuation with orforglipron, with an odds ratio of 4.1 for stopping due to any adverse event and 13.9 for stopping due to gastrointestinal side effects.

Five of the authors are Novo Nordisk employees and shareholders, two more work for a consultancy Novo paid to run the analysis, and Novo makes the drug that won. That does not make the result false. It does mean I apply a discount. The direction is plausible and roughly matches the gap between the two labels. The magnitude I would not quote to a patient as fact. And that gastrointestinal odds ratio of 13.9 has a confidence interval running from 2.0 to 96.0, which is another way of saying the study could not pin it down.

There is one true head-to-head, and it points the other way. In adults with type 2 diabetes, orforglipron beat oral semaglutide on weight loss (7). That trial used semaglutide at 7 mg and 14 mg, well under the 25 mg weight-management dose, in a different population, for a different purpose. It answers a different question than the one you are asking.

Birth control is the difference nobody mentions

This is the most actionable difference between the two drugs and it almost never comes up in the coverage.

The Foundayo label instructs patients on oral hormonal contraceptives to switch to a non-oral method, or to add a barrier method for 30 days after starting the drug and for 30 days after every dose escalation (5). Count the escalations. With six strengths, somebody climbing to the top dose is looking at several separate 30-day windows where their pill alone is not considered reliable. Non-oral hormonal contraception is not expected to be affected.

The Wegovy tablet label carries no equivalent instruction. Its pharmacokinetic studies found no clinically significant interaction with ethinyl estradiol and levonorgestrel (4).

For a woman in her twenties or thirties on a combined oral contraceptive who does not want a pregnancy, that single difference outweighs three percentage points of average weight loss. I bring it up before either drug gets prescribed, not after.

The other interactions that quietly decide this

Orforglipron is cleared through CYP3A4, and the label puts real fences around that (5). On a strong CYP3A4 inhibitor, the maximum Foundayo dose drops to 9 mg. Clarithromycin raised orforglipron exposure 3.5-fold in a study. Going the other way, carbamazepine cut exposure by 82 percent and efavirenz by 61 percent, so strong inducers are to be avoided and moderate ones need the dose pushed up while you watch whether it still works. Strong inhibitors that also block OATP1B, ritonavir being the example the label gives, are to be avoided outright. And simvastatin is capped at 20 mg a day alongside it.

The semaglutide tablet has a shorter list but one that matters in my practice. A single 600 mcg dose of levothyroxine taken with it produced a 33 percent rise in total thyroxine exposure (4). Add the 30-minute rule on top, which pushes every other morning medication back, and a patient on thyroid replacement plus a few other dailies has a genuine scheduling problem.

If someone comes to me on carbamazepine, or on ritonavir-boosted therapy, Foundayo is awkward enough that I start elsewhere. If someone is on levothyroxine and already struggles to take it correctly, I think hard before adding a second pill with its own empty-stomach window.

Side effects

Both drugs hit the gut, and both labels say so plainly.

Foundayo’s pooled safety data runs nausea at 26 percent, 34 percent and 35 percent across the 5.5, 9 and 17.2 mg doses against 10 percent on placebo (5). Vomiting climbs from 13 to 24 percent against 4 percent. Constipation runs 20 to 27 percent against 9 percent, and diarrhea 21 to 25 percent against 11 percent. Hair loss shows up at 4 to 5 percent against 2 percent, which patients ask me about more than the numbers would suggest.

The Wegovy tablet label describes side effects similar to the injection, and adds a few tablet-specific figures (4). Just under 7 percent of patients stopped the drug for an adverse reaction, against about 6 percent on placebo. Severe gastrointestinal reactions occurred in 2 percent of tablet patients and no placebo patients. Dysesthesia, meaning abnormal or unpleasant sensation, was reported in 5 percent of tablet patients and in nobody on placebo. That last one is not something I had on my radar before reading the label, and it is worth mentioning to a patient who calls about odd skin sensations rather than writing it off.

Both drugs carry a boxed warning about thyroid C-cell tumors and are contraindicated in anyone with a personal or family history of medullary thyroid carcinoma or MEN 2 (4)(5).

If you have heart disease, the answer is already made

Wegovy tablets carry an approved indication to reduce the risk of major adverse cardiovascular events, meaning cardiovascular death, non-fatal heart attack and non-fatal stroke, in adults with established cardiovascular disease and either obesity or overweight (4). The wording is identical to the injection’s.

Foundayo has no cardiovascular outcome indication. Its cardiovascular outcomes trial has not reported.

For a patient who has already had a heart attack or a stroke, that settles it. I go to semaglutide, and the only remaining question is tablet or injection.

How I actually choose

If you are the patient reading this, the useful question is not which drug is stronger. It is which one you will still be taking in a year. The 30-minute waiting period for the semaglutide tablet sounds minor when we talk it through on a video visit, and it trips people up in real life. I have watched patients lose ground on oral semaglutide because weekday mornings made the timing rules impossible to follow, and the drug cannot work from inside the bottle. If your mornings are chaotic, say so out loud when we talk. That is clinical information, not an excuse.

If you are a prescriber, I would frame the choice around four things before efficacy. Established cardiovascular disease points to semaglutide on the label. An oral contraceptive points away from orforglipron, or at least commits you to counseling a barrier method through every escalation. A CYP3A4 problem, especially an enzyme inducer, makes orforglipron hard to dose. Levothyroxine and a crowded morning pill box make the semaglutide tablet hard to take. What is left after those four filters is usually a clear answer, and in my experience the efficacy gap is the least useful thing to lead with.

What this costs right now

Both manufacturers run tiered self-pay pricing that starts low at the smallest dose and rises as you titrate up, and both have promotional rates on their lower strengths that are scheduled to end on December 31, 2026. Because these terms change faster than I can keep a blog post current, check the two official pages directly rather than trusting a number you read anywhere, including here: LillyDirect for Foundayo (8) and NovoCare for Wegovy (9).

What I can tell you from prescribing both is operational. I haven’t run into a prior-authorization fight or a stocking problem with Foundayo yet. Most of what I prescribe goes through LillyDirect on cash pay, because it has been one of the cheaper options on the table. Patients who have real insurance coverage tend to ask for injectable Wegovy or Zepbound instead, and I do not talk them out of it. For a fuller breakdown of cash prices across the whole class, including the injections, see my separate post on cash pay options.

The Bottom Line

Two pills, both approved, both effective, and the deciding factors are mostly not about weight loss. The semaglutide tablet takes off a bit more weight in the label data, carries a cardiovascular indication, and demands an empty stomach and a 30-minute wait every single morning. Foundayo asks nothing of your schedule, has a far larger trial behind it, and brings a contraception instruction and a list of drug interactions that rule it out for some people entirely.

Bring your actual medication list and your actual morning routine to the visit. Those two things will pick the drug faster than any comparison chart.

Sources

1. FDA approves Lilly’s Foundayo (orforglipron), the only GLP-1 pill for weight loss (Eli Lilly): https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-foundayotm-orforglipron-only-glp-1-pill

2. FDA approves Novo Nordisk’s Wegovy pill, the first and only oral GLP-1 for weight loss in adults (PR Newswire): https://www.prnewswire.com/news-releases/fda-approves-novo-nordisks-wegovy-pill-the-first-and-only-oral-glp-1-for-weight-loss-in-adults-302648344.html

3. Current Understanding of SNAC as an Absorption Enhancer: The Oral Semaglutide Experience (Clinical Diabetes, American Diabetes Association): https://diabetesjournals.org/clinical/article/42/1/74/153538/Current-Understanding-of-Sodium-N-8-2

4. WEGOVY (semaglutide) injection and tablets, US prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b

5. FOUNDAYO (orforglipron) tablets, US prescribing information (Eli Lilly): https://uspl.lilly.com/foundayo/foundayo.html

6. Michalak W, Bøg M, Bendixen T, Chowdhury R, Cowley P, Laugesen C, et al. Oral Semaglutide 25 mg Versus Orforglipron 36 mg in Obesity: A Population-Adjusted Indirect Treatment Comparison. Diabetes, Obesity and Metabolism. 2026;28(8):7247-7256: https://pubmed.ncbi.nlm.nih.gov/42225305/

7. Orforglipron Outperforms Oral Semaglutide in Head-to-Head Type 2 Diabetes Trial (AJMC): https://www.ajmc.com/view/orforglipron-outperforms-oral-semaglutide-in-head-to-head-type-2-diabetes-trial

8. Foundayo self-pay pricing (LillyDirect): https://www.lilly.com/lillydirect/foundayo

9. Wegovy self-pay pricing (NovoCare): https://www.novocare.com/

10. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment (New England Journal of Medicine, ATTAIN-1): https://www.nejm.org/doi/full/10.1056/NEJMoa2511774

A pharmacist standing in front of shelves of medicines

Compounded Semaglutide and Tirzepatide: What to Know Now

On October 17, 2025September 29, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

When patients ask me about compounded weight loss drugs like semaglutide and tirzepatide, I take a deep breath. The topic is complicated and keeps changing. I won’t just tell patients to avoid them. They’re already looking for these options, and my job is to help them navigate the risks safely.

Dr. Beverly Tchang’s “swim safely” analogy fits well. We can’t stop people from diving into the ocean of compounded products, but we can at least give them floaties: information, caution, and tools to make better decisions. (Tchang, Medscape)

Here’s how I explain it to patients and colleagues, updated with the most recent data.

Why compounded versions exist

When semaglutide and tirzepatide injections were in short supply a few years ago, patients turned to compounding pharmacies that offered custom formulations, often at a lower price. (GoodRx)

In late 2024, the FDA ended the declared shortage of tirzepatide. (Stat News) By early 2025, semaglutide (Ozempic and Wegovy) followed. Once the shortages ended, enforcement ramped up against compounded versions. (GoodRx)

Now, compounded versions are only legal in narrow circumstances, such as when a patient has a medical need that can’t be met by an approved product. (GoodRx)

In December 2024, the FDA sent warning letters to several companies selling unapproved GLP-1 drugs labeled “for research use only.” (Reuters) Some of these contained no active ingredient, incorrect salt forms, or inconsistent potency. (Verywell Health)

Key risks and what to look for

Not all compounding pharmacies operate at the same standard. A friendly local pharmacist doesn’t necessarily mean the product is safe. Dr. Tchang’s checklist gives a good framework for evaluating any compounded GLP-1 medication. A simplified version: look for a pharmacy where the medication is prescribed by a licensed provider, there are no disciplinary actions on file, the pharmacy has been in business for more than a year, only semaglutide base is used (not a salt form), and the facility is FDA-registered or FDA-inspected; it should also be able to ship sterile drugs safely to all 50 states.

If a compounding pharmacy cannot meet these criteria, that’s a red flag. Ask directly for documentation. If they can’t provide it, walk away.

Some compounders also mix in vitamins or preservatives to make their product “different” from the brand name; that may sound harmless, but combining untested additives with peptides can change how the drug behaves. (GoodRx)

A few are promoting oral or sublingual forms of semaglutide and tirzepatide. These seem attractive for patients who don’t like injections, but they haven’t been validated in clinical trials, and absorption is unpredictable. (Omada Health)

Even small changes in formulation or dosing can interrupt treatment and cause rebound weight gain or side effects.

How I approach this with patients

When a patient says, “I found a compounding pharmacy that sells it for half the price,” I acknowledge their concern. Access and cost are real issues. But I explain that the regulatory situation has changed. If an FDA-approved version is available, that’s the standard we should use first.

I encourage patients to ask the pharmacy for their certificate of analysis, sterility test results, and ingredient source; if the pharmacy hesitates or says it’s proprietary, that’s enough reason to stop.

One patient of mine was on a compounded semaglutide microdose that wasn’t commercially available, at least as she described it to me. I never could pin down what she was actually getting. The compounder wouldn’t release potency data either. We moved her to a low-dose commercial version instead. Weight loss slowed a little. Safety and consistency improved, and I knew what was in the pen.

We also reviewed manufacturer assistance programs and insurance coverage. Many patients don’t realize that drug makers often cap out-of-pocket costs for brand medications; cost confusion is one of the biggest drivers behind compounded use.

The FDA’s BeSafeRx campaign

The FDA has an ongoing public safety campaign called BeSafeRx, designed to help patients and providers verify the legitimacy of online pharmacies and compounded drug sources; it offers tools to check pharmacy licenses, identify red flags, and report suspicious products.

It’s a good resource for anyone considering buying compounded or online medications; I often share it directly with patients so they can see what trustworthy sourcing looks like.

You can find the BeSafeRx information at:

https://www.fda.gov/drugs/buying-using-medicine-safely/besaferx-your-source-online-pharmacy-information

What’s changed recently

The REDEFINE trial (NEJM, 2025) studied cagrilintide combined with semaglutide (CagriSema) and showed about 20.4 percent weight loss over 68 weeks, compared with 14.9 percent with semaglutide alone; that kind of data will shape treatment algorithms going forward. GoodRx reports that the FDA’s grace period for compounding GLP-1s has officially ended for both tirzepatide and semaglutide, though some pharmacies still market “custom” or “non-identical” formulations, and regulators are watching closely.

Approach this without judgment if you’re a clinician. Patients are trying to find affordable solutions. And they often trust what they see on social media more than official channels; we can help most by staying informed, asking questions, and documenting carefully. Patients should be cautious for a different reason. Ask your provider to review any compounded medication before you use it, make sure your pharmacy meets every item on that checklist, and use resources like the FDA’s BeSafeRx to verify safety.

Knowledge and transparency remain the best safeguards.

Why Weight Loss Plateaus Happen and How to Break One

On September 18, 2025September 29, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

Most people losing weight eventually hit a plateau. The number on the scale stops moving, sometimes for weeks, and it can feel like something has gone wrong. Nothing has. Plateaus happen because of biology: at a lower body weight the body burns fewer calories than it used to, and hormones like leptin shift in ways that increase hunger, slow resting metabolism, and make the next five pounds harder to lose than the first fifty.

Handling a plateau matters more than trying to prevent one. In my practice, we look at the medication plan, nutrition, and activity together. Sometimes the answer is moving to a higher dose of semaglutide (Wegovy) or tirzepatide (Zepbound), switching between the two, or starting orforglipron (Foundayo) if a patient hasn’t tried it yet. In my experience two patterns show up most. An early one within the first month, when patients think the medication has stopped working but it’s actually just been started low to help the body adjust rather than to drive weight loss yet. And a later one once someone’s at the highest dose they can tolerate, when exercise drops off and food choices drift back to where they started. Other times the prescription isn’t the issue at all. Small changes in nutrition, like adding more protein, cutting liquid calories, or tightening portions, can make the difference.

Physical activity plays a role too. The National Weight Control Registry has shown that people who keep weight off long term usually exercise about an hour a day. That doesn’t mean a treadmill. Brisk walking, biking, swimming, anything that raises the heart rate consistently, counts, and strength training helps by preserving lean muscle and keeping metabolism steady.

Daily habits matter. People who maintain weight loss tend to eat breakfast every day and weigh themselves regularly. They also tend to watch less television, generally under ten hours a week. None of this is a rigid rulebook. It’s structure, and structure makes it harder to drift back into old patterns.

If you hit a plateau, don’t get discouraged. Treat it as a signal to check in and adjust, not to quit. My first move is usually education, making sure the patient understands what the medication is actually doing and why the scale has stalled. If food noise is still loud after that conversation, I’ll increase the dose or add another medication, but not before we’ve gone back through lifestyle and food choices together. Whatever the starting point, there are proven strategies to get moving again.

Reference: National Weight Control Registry. www.nwcr.ws

Binge Eating Disorder Signs and Treatment in Adults and Kids

On September 17, 2025September 29, 2026 By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

Binge Eating Disorder, or BED, is one of the eating disorders I screen for most often in practice. Clinicians define it as repeated episodes of eating a large amount of food in a short period of time while feeling a loss of control during the episode. BED involves episodes that feel compulsive: the person cannot stop eating even when full or uncomfortable. This goes well beyond a second helping at dinner or an indulgent dessert.

The diagnostic criteria for BED require both that large amounts of food are consumed in a discrete time frame and that there is a sense of loss of control while eating. The episodes are also linked to behaviors such as eating more rapidly than normal, eating until uncomfortably full, eating when not hungry, eating alone because of embarrassment, and feeling disgusted or guilty afterward. At least three of those behaviors must be present. The episodes need to occur at least once a week for three months, cause distress, and they are not followed by purging behaviors like in bulimia.

Here’s a hypothetical that illustrates the pattern: someone sits down in the evening and works through an entire pizza and a half-gallon of ice cream in under two hours, not from hunger but because they can’t stop. They feel physically ill afterward. Ashamed, too. The cycle repeats weekly or more often. I’ve seen a real version of this on video visits. One of my patients was managing things with intermittent fasting, and it worked in the sense that the scale moved, but every time the eating window opened back up, they took in way more calories than they needed. The fast itself was setting up the binge.

Children complicate this picture. For kids under 12, researchers have proposed a related diagnosis called Loss of Control Eating Disorder, or LOC-ED (Tanofsky-Kraff et al., 2008). The issue is that children may not consume amounts of food that adults would consider objectively large, but they still experience the same loss of control. In this group, the definition focuses on the subjective sense of being unable to stop eating. The proposed criteria mirror those of BED but apply specifically to children younger than 12. The episodes still need to happen at least once a week for three months and cause distress.

Picture a hypothetical case in pediatrics: a 10-year-old who sneaks into the kitchen at night, eats snack foods quickly, and can’t stop once started. The amount might look modest by adult standards. For a child, it’s significant. What matters is the loss of control, not the portion size. Wrappers hidden in the trash. A refusal to eat breakfast the next morning. Those are often the only clues a parent gets.

Treatment is available for both BED and LOC-ED. For adults with BED, the most evidence supports cognitive behavioral therapy, which helps patients identify triggers, restructure eating patterns, and address guilt and shame. Interpersonal therapy has also been shown to help, especially when social stress is a driver. Some patients benefit from medications. SSRIs have modest benefit for binge frequency, and lisdexamfetamine is the only medication currently approved by the FDA for BED in adults. Nutritional counseling and structured meal planning are usually part of the approach.

I should be direct about where I actually fit into this picture. I don’t manage BED treatment myself. Real treatment leans heavily on behavioral health, and in my current telemedicine positions I don’t have the coordination with a therapist or eating-disorder specialist that this really requires. What I do is screen for it on video visits: ask the direct questions, name what I’m seeing, and refer out from there.

For children with LOC-ED, treatment recommendations are less formalized since the diagnosis itself is still considered research-based. The focus is often on family-based behavioral therapy, involving parents in setting up structured eating schedules and reducing situations where loss of control is most likely to occur. Addressing mood or anxiety symptoms is important, since these are often linked to eating episodes. Nutrition support is also key, both for the child and for parents trying to guide food choices. Medications are not first-line in children.

Recognizing BED or LOC-ED is important because both conditions are linked to higher rates of obesity, depression, and medical complications if untreated. Many people don’t come forward because of shame or because they don’t realize their pattern is a diagnosable disorder. Asking direct questions about eating behaviors, especially around loss of control, can uncover these conditions and open the door to treatment.

If this description fits you or someone you know, talk with a healthcare provider. Early recognition, especially in children, can change the trajectory and reduce the risk of chronic problems.

Why your compounded supply is drying up

Why can’t I just convert my compounded dose?

Restart low, or match the dose?

What I would gather before the video visit

What restarting will feel like

What will the brand version cost?

Pills as a way out

Gray-market sellers and “research use” vials

If you are the patient

If you are the clinician

The Bottom Line

Related Reading

Sources

Why you want to stop matters more than the fact that you want to stop

What the evidence actually shows

It is physiology, not a character flaw

Most people stop anyway

What I actually do: lower the dose rather than stop

When the reason is cost

Protecting muscle

When I bring up the long-term question, and why not sooner

When I support stopping

Restarting

For clinicians

The Bottom Line

Related Reading

Sources

What the Label Now Says

The Trial Behind It

Where This Leaves Ozempic, Wegovy, and Zepbound

For Patients

The Practical Question for Prescribers

The Bottom Line

Related Reading

Sources

The scale was never the menopause story

Where the fat goes

Your metabolism did not crash at 50

Why it happens, and how much of that is known

What shows up on your labs

Lift something heavy, then eat enough protein to use it

The strongest diet trial here is a prevention trial

Hormone therapy, stated precisely in both directions

GLP-1s and the muscle question

What is oversold

If you are the patient reading this

For the clinicians

The Bottom Line

Related Reading

Sources

What the data actually shows

What’s changing in how we prescribe

What’s coming that may change this conversation further

The bottom line

Related Reading

Why the two pills work so differently in your body

What the labels actually say, and why the number in your news feed is wrong

The only comparison anyone has run, and who paid for it

Birth control is the difference nobody mentions

The other interactions that quietly decide this

Side effects

If you have heart disease, the answer is already made

How I actually choose

What this costs right now

The Bottom Line

Related Reading

Sources

Why compounded versions exist

Key risks and what to look for

How I approach this with patients

The FDA’s BeSafeRx campaign

What’s changed recently

Related Reading

Related Reading

Related Reading