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 hand mirror, a pair of folded cotton socks and a home glucose meter with a lancet on a sunlit wooden table

What Does Diabetes Do to Your Skin?

On August 29, 2026August 30, 2026 By Dr. Scott RennieIn Skin & Wound CareLeave a comment

Skin is the one organ I can actually see on a video visit. No stethoscope, no palpation, no reaching across the desk. Just a camera, whatever light the patient happens to have, and a screen. That limitation has made me pay closer attention to skin than I did when I worked in urgent care, because on video it is often the first physical evidence that something metabolic is going on.

Between 30 and 70 percent of people with diabetes develop a skin problem attributable to the disease at some point (1). That is an enormous range, which tells you the studies are measuring different populations and different definitions rather than anything precise. Take the range as what it is, a signal that this is common, not a statistic to quote back to anyone.

What follows is what I look for, why it matters, and where I think the usual advice is weaker than it sounds.

The velvet patch on the back of the neck

Acanthosis nigricans is the one I care about most, because it is visible, it is early, and patients almost never bring it up. Dark, thickened, velvety skin in the folds. Back of the neck, armpits, groin, under the breasts. Patients describe it as dirt that will not wash off, and some have been scrubbing at it for years.

The mechanism is insulin. Hyperinsulinemia drives IGF-1 receptor activation on keratinocytes and fibroblasts, which proliferate (2). So the plaque is a rough readout of how much insulin the pancreas has been pushing out to keep glucose in range. It shows up before the fasting glucose does. Sometimes years before.

Skin tags travel with it and share the same driver (2). A patient with acanthosis nigricans and a crop of acrochordons on the neck and axillae is telling you about their insulin resistance without a single lab drawn.

Here is where I differ from what patients are usually told. Dermatology handles acanthosis nigricans as a cosmetic complaint and offers topical retinoids, urea, sometimes laser. Those do something to the appearance. None of them touch the reason it is there. I follow the ADA rule and screen every adult from 35 regardless of BMI, and when I see that patch I do not wait for the birthday. I check an A1c.

It also improves. Not overnight, and not completely in everyone, but weight loss and improved insulin sensitivity soften the plaques over months. That is worth telling someone who has been scrubbing their neck since high school.

Skin tags carry information

I have a whole post on what skin tags are and what they look like, and it gets steady traffic from people worried about a lesion. What that post does not do is explain why someone in their thirties suddenly has fifteen of them.

Friction is part of it. Insulin is the rest.

What high glucose actually does to a wound

This one deserves its own post and is getting one. The short version: glycosylation impairs neutrophil and macrophage function, which prolongs the inflammatory phase instead of letting the wound move on to proliferation. Fibroblast activity drops, VEGF expression drops, matrix metalloproteinases go up, collagen density falls. Layer underlying vascular disease on top of that and you have a wound that stalls.

The practical consequence is that a cut on someone with an A1c of 11 is a different clinical problem than the same cut on someone with an A1c of 6, even though it looks identical on camera.

The infections that come with the territory

Candidal intertrigo lives in the skin folds, and the bigger the fold the more reliably it shows up. Beefy red, satellite lesions at the edge, itching or burning rather than pain. Patients treat it with hydrocortisone from the drugstore, which makes it worse, and then arrive convinced they have an allergy.

Tinea in all its addresses, feet, groin, nails. Onychomycosis in particular is stubborn and, in a diabetic foot, is not merely a nuisance: a thickened dystrophic nail is a pressure point and a portal.

Then cellulitis. Elevated glucose, impaired barrier, and a break in the skin from a fissure or a fungal infection between the toes. My rule for an abscess is that it goes out for drainage rather than getting empiric antibiotics from me over video, and I am firmer about that than some colleagues are.

Hidradenitis suppurativa, and what changed

HS has been badly served for a long time. Painful nodules and sinus tracts in the axillae, groin and under the breasts, frequently mistaken for recurrent boils for years before anyone names it. The association with obesity is strong and it is not a coincidence of body habitus alone; the inflammatory biology overlaps.

What has changed recently is incretin therapy. Multiple cohorts and case series now report reduced disease activity, fewer flares and less pain in HS patients treated with GLP-1 receptor agonists, alongside the expected BMI reduction (3). A cross-sectional survey found roughly two thirds of respondents reporting improvement in HS-specific measures (4).

I want to be honest about the strength of that evidence, because the enthusiasm is running ahead of it. These are retrospective cohorts, case series and patient-reported surveys. There is no adequately powered randomized trial with standardized background therapy. The signal is consistent enough that I take it seriously in a patient who has both conditions and would be a candidate for the drug anyway. It is not a reason to start an incretin in someone whose only indication is HS.

The foot

Somewhere between 19 and 34 percent of people with diabetes will develop a foot ulcer in their lifetime (5). The number that changed how I talk to patients is not that one, though. It is what happens after the ulcer closes: roughly 40 percent recur within one year, close to 60 percent within three years, and 65 percent within five (5).

Armstrong and colleagues argued from that data that a patient whose wound has closed should be thought of as in remission rather than healed (5). I use that word deliberately with patients now, because a person who believes they are healed puts the mirror away and stops looking at the bottom of their feet, while a person who believes they are in remission keeps checking, keeps wearing the shoes that were fitted for them, and calls about a blister on the day it appears rather than three weeks later when it has become something else. Remission gets you daily foot checks. Healed gets you a pair of sandals and a summer of walking on hot pavement with neuropathy.

That framing does more work in a fifteen-minute visit than any amount of education about glycemic targets.

What I ask for on video

Skin over a camera is genuinely hard. Autofocus hunts, phone processing smooths texture, and the color balance depends on whether someone is under a kitchen light or a window.

So I ask for two photographs of anything I need to actually assess. One from a distance, far enough back to show where the lesion sits and what the surrounding skin looks like, and one macro, as close as the phone will focus without blurring. Multiple angles if there is any elevation to it. The blur problem is the single most common reason I have to ask twice, and it is almost always because the patient is closer than the lens can handle. Backing up six inches fixes it.

For anything in a fold, I want the fold held open in the shot. For feet, I want the sole and between the toes, which usually means someone else holds the camera.

For patients

If the skin on the back of your neck or in your armpits has gone dark and thick and will not scrub off, that is not hygiene, and it is worth an A1c. If you are getting skin tags in bunches, same. If you have painful recurring lumps in your armpits or groin that have been called boils for years, ask specifically about hidradenitis suppurativa by name, because that is often what gets the diagnosis moving.

And if you have diabetes, look at your feet every day. Every day, including between the toes, including the bottom, using a mirror or a family member if you cannot see them.

For colleagues

Acanthosis nigricans in an adult is a screening prompt, not a dermatology referral. Check the A1c and the lipids before you send them for cosmetic treatment of the plaque.

The GLP-1 and HS literature is worth knowing about and worth being careful with. When a patient with both conditions asks whether the drug will help their skin, the honest answer names the cohorts, names their design, and stops short of promising anything.

On the foot, adopt the remission language. It changes adherence in a way that repeating ulcer statistics does not.

The Bottom Line

Skin is where metabolic disease announces itself, often years before a lab does. A velvety patch behind the neck, a crop of skin tags, a yeast infection in a fold that keeps coming back, a nail that will not clear. None of those are dermatologic curiosities to be treated in isolation. They are all the same disease showing up at the surface, and treating the surface without asking why it is there wastes the information. Check the A1c. Look at the feet. And when a wound closes on a diabetic foot, say remission, not healed.

Sources

1. Vâță D, et al. Cutaneous Manifestations Associated with Diabetes Mellitus: A Retrospective Study. Diseases. 2023;11(3). PMID 37606477. https://pubmed.ncbi.nlm.nih.gov/37606477/

2. Marchand L, et al. All about skin manifestations of insulin resistance and type 2 diabetes: acanthosis nigricans and acrochordons. Postgrad Med J. 2020;96(1134):237. PMID 31611265. https://pubmed.ncbi.nlm.nih.gov/31611265/

3. Rao S, et al. Skin Impacts and Tradeoffs of GLP-1 Therapy: Improved Patient-Reported Outcomes of Inflammatory Skin Disease. Dermatol Ther (Heidelb). 2026. PMID 42579223. https://pubmed.ncbi.nlm.nih.gov/42579223/

4. Javaheri ED, et al. Impact of GLP-1 Receptor Agonists on Hidradenitis Suppurativa: A Cross-Sectional Survey. Int J Dermatol. 2026 Jul 16. PMID 42461155. https://pubmed.ncbi.nlm.nih.gov/42461155/

5. Armstrong DG, Boulton AJM, Bus SA. Diabetic Foot Ulcers and Their Recurrence. N Engl J Med. 2017;376(24):2367-2375. PMID 28614678. https://www.nejm.org/doi/10.1056/NEJMra1615439

6. International Working Group on the Diabetic Foot. IWGDF Guidelines on the prevention and management of diabetes-related foot disease, 2023. https://iwgdfguidelines.org/guidelines-2023/

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

Plain grey canvas walking shoes, a smooth stone and an unlabeled clear glass bottle on a wooden floor in daylight.

Longevity Medicine: What Actually Works, and What Doesn’t

On August 24, 2026September 11, 2026 By Dr. Scott RennieIn Longevity & Healthy AgingLeave a comment

Longevity medicine is a wide field, and most of it is not what gets marketed. This is a review of what the evidence actually supports, from fitness and blood pressure to the drugs and supplements patients ask about by name.

Patients bring me longevity questions on video, which is how every visit I do happens. It usually arrives as a general question about what I recommend for living longer, followed by one specific thing they read about online. Phosphatidylcholine. Rapamycin. GLP-1 medications.

Here is the part that disappoints almost everybody. The things with the largest measured effect on how long you live are cheap, boring, and nobody can patent them, so nobody sells them. The drugs people ask about by name sit lower on the list, and several sit there with no human results at all. That does not make them worthless. I prescribe GLP-1 receptor agonists and think they are the most important thing to happen to metabolic medicine in my working life. The point is ordering.

What actually works, and it is not a close call

Start with cardiorespiratory fitness, which means how well your heart and lungs move oxygen while you work hard. Nothing else here comes close to it.

Mandsager’s team at Cleveland Clinic followed 122,007 patients who had treadmill tests between 1991 and 2014. The fittest group came out at an adjusted hazard ratio of 0.20 against the least fit (1). A hazard ratio compares the risk in one group against another. Anything under 1.00 means less risk, so 0.20 means the fittest people died at roughly a fifth the rate of the least fit. That is an enormous gap.

That paper also produced the line that being unfit is worse than smoking, and here is the correction. It reported hazard ratios of 1.41 for smoking and 1.40 for diabetes sitting next to 1.41 for below-average fitness (1). Those are similar sizes inside one model. Nobody raced them against each other, and a poor treadmill result is partly a measure of disease nobody has found yet. The pattern does hold up elsewhere, at roughly 14 percent lower death rates for each one-MET gain in fitness (2). A MET is a unit of effort, and one MET is about what your body burns sitting still, so gaining one is real training.

Resistance training is the second lever, and the useful finding is where it stops. Momma pooled dozens of studies and found that any muscle-strengthening work was linked to a 10 to 17 percent lower risk of death, heart disease, cancer and diabetes. The benefit peaks at 30 to 60 minutes a week and flattens after 60 (3). Two half-hour sessions. That is the whole prescription, and the flattening is the part fitness content never mentions, because there is no business in telling somebody they are done.

Grip strength comes at it sideways. In PURE, across 139,691 adults in 17 countries, the death rate rose with a hazard ratio of 1.16 for every 5-kg drop in grip (4). Grip stands in for how much muscle you carry. Nobody should go train their hands.

Nobody ever counted to ten thousand

Paluch pooled 15 cohorts and found the benefit of daily steps levels off around 6,000 to 8,000 for adults 60 and older, and 8,000 to 10,000 under 60 (5).

Here is my one digression. The 10,000 figure has no medical origin whatsoever. It came from a pedometer sold in Japan in 1965, the manpo-kei or ten-thousand-step meter, named partly because the Japanese character for ten thousand looks a bit like a person walking. A marketing name became a health target millions of people feel guilty about missing. Nobody ever checked the math.

The interventions with no sales force

SPRINT assigned people at random to a tight blood pressure goal, under 120 on the top number, against the usual goal of under 140. All-cause mortality, meaning death from any cause, came out at a hazard ratio of 0.73, with an NNT of about 90 over a median of 3.26 years (6). NNT is the number needed to treat. Hold 90 people to the tighter goal for a bit over three years and one of them lives who otherwise would not have. Nothing sold as a longevity supplement has an NNT, because none of them has ever been tested against death.

Quitting smoking gives back more life still. From Jha’s 201,248 US adults, quitting between 25 and 34 gets back about ten years, and quitting in your late fifties still returns four (7).

Sleep follows a U-shaped curve, with the lowest risk near seven hours and the risk climbing faster on the long side, up to a relative risk of 1.37 at ten hours (8). What I want people to stop expecting is a heart benefit from CPAP. SAVE assigned 2,717 adults with moderate-to-severe sleep apnea and known heart disease at random, and the main result came back at HR 1.10, flatly null, which means no difference at all (9). None. CPAP treats symptoms. Say that out loud when you prescribe it.

Then the one physicians skip. Holt-Lunstad’s pooled work put the odds of dying at 1.29 for social isolation and 1.26 for loneliness, with living alone at 1.32 (10). The line about loneliness equalling fifteen cigarettes a day restates those same odds rather than adding a calculation, so hold it loosely.

Diet belongs here too, and PREDIMED is where the honest version lives. Its Mediterranean groups cut the main heart outcome by roughly 30 percent, which is a real result, though the trial was never built to measure death from any cause, and it was pulled and republished in 2018 after an audit found problems with how 1,588 of 7,447 people were assigned (11). Eat that way for your heart. It does not follow that it buys you years.

Weight loss, and what SELECT actually settled

For years there was no good answer on whether losing weight on purpose lowers the death rate. Look AHEAD assigned 5,145 adults with type 2 diabetes at random to an intensive diet and exercise program, held weight loss near 6 percent, and returned a heart outcome of HR 0.95 before stopping for futility (12). Well conducted. Well powered. Null.

SELECT changed that without finishing it. 17,604 adults with overweight or obesity and known heart disease, no diabetes; major heart events hit 6.5 percent on semaglutide against 8.0 on placebo, HR 0.80 (13). All-cause mortality came in at HR 0.81, 95% CI 0.71 to 0.93, and gets quoted everywhere as proof. It is not, and the reason is worth knowing. The trial used hierarchical testing, which means the questions were ranked in advance and answered in order, and once one of them fails, nothing below it counts as proof anymore. That chain broke a step earlier, at heart-related death, HR 0.85, CI 0.71 to 1.01, P=0.07. So the rule bit. So the death result is a strong hint. I think the effect is probably real. I will not tell you it has been proven.

The prescriptions people ask me for by name

GLP-1 receptor agonists are the only drugs here I reach for gladly, and I use them for obesity and its complications. FLOW cut its main kidney outcome to HR 0.76 in 3,533 patients with type 2 diabetes and chronic kidney disease, stopped early because the drug was plainly working, and turned up roughly 20 percent lower all-cause mortality among the secondary results, though I could not confirm the exact confidence interval on that one (14). SURMOUNT-MMO is testing tirzepatide against a combined outcome that includes death from any cause, and it has reported nothing (15). Orforglipron, approved April 2026 as the first pill in the class, has no death data either (16). I prescribe it. I do not pretend it has evidence it does not have.

The catch is muscle. Across these trials, lean tissue was about 45 percent of the weight lost with semaglutide in STEP-1 and about 26 percent with high-dose tirzepatide in SURMOUNT-1 (17). Lean tissue is mostly muscle. Losing close to half your weight as muscle matters in a 68-year-old whose grip is already borderline. It matters a lot. Protein at 1.0 to 1.2 g/kg/day is the geriatric target, and in older patients that is the number I use (18). For most other adults the adequate intake sits higher, and I aim for 80 to 120 grams a day, or 1.6 g/kg/day. Resistance training two to three days a week, covering all major muscle groups, is what decides how much of that muscle survives the loss.

Metformin I would not prescribe to a person without diabetes for longevity. The famous claim is Bannister’s 2014 comparison, which adjusted for nothing: 14.4 deaths per 1,000 person-years among metformin-treated diabetics against 15.2 in matched non-diabetic controls (19). A twenty-year reanalysis found the reverse (20). Most of that first result is confounding by indication, meaning the people who stay on metformin alone were healthier to begin with, in better shape before anyone handed them a pill, so the drug quietly takes credit for a head start it never gave them. TAME was meant to settle it, and as of August 2026 AFAR’s own page still describes it as seeking funding, enrollment not begun (21). Two randomized trials meanwhile found metformin blunting the gains older adults get from exercise, cutting improvements in how well muscle cells make energy and in fitness (22), and losing to placebo on lean mass at 1,700 mg/day over 14 weeks of resistance training (23). Fitness and muscle are the two biggest levers in this piece. Dulling both to chase a result nobody has repeated is a bad trade.

Rapamycin. PEARL assigned 114 adults aged 50 to 85 at random to placebo or 5 or 10 mg of weekly compounded rapamycin for 48 weeks and found it tolerable, with side gains in lean tissue and self-reported pain in women at the higher dose (24). The trial was funded and run by AgelessRx, a longevity telehealth company that sells the thing being studied. Human data on living longer does not exist. I would not write it for this. Senolytics have less. A senolytic is a drug built to clear out worn-out cells that have stopped dividing but keep irritating the tissue around them, and no senolytic has produced any human data on health or lifespan. Everything published so far is safety work (25).

Statins I treat as cholesterol drugs, which is what the guidelines say they are; PREVENTABLE reports in December 2026 on adults over 75 without heart disease (26).

Aspirin is the cleanest example of a longevity assumption failing once somebody randomized it. ASPREE tested low-dose aspirin in healthy older adults for primary prevention, meaning people who had never had a heart attack or a stroke. They died at a higher rate on aspirin, HR 1.14, driven mainly by cancer death, with more major hemorrhage, meaning serious bleeding, and no heart benefit (27). The primary endpoint, which is the single question a trial is built to answer, was years lived without disability, and it showed nothing (28). If you take a daily aspirin with no vascular disease because someone suggested it in 2006, raise it at your next visit.

The supplement aisle, and phosphatidylcholine in particular

NAD+ precursors sell on a mechanism and a biomarker. A biomarker is something you can measure in blood that may or may not track with how you feel or how long you live. Nicotinamide riboside raises whole-blood NAD+ up to 142 percent at 1,000 mg over two weeks, in an open-label study with no clinical endpoint (29). A review of ten NMN trials found the same shape: NAD+ rises, a thin signal on physical performance, nothing resembling a disease or death outcome (30). Tested against thinking and memory in people with mild cognitive impairment, it moved the blood chemistry and nothing else (31).

The ones people tell me they are already on are NAD+ precursors, NMN or NR, and resveratrol. Resveratrol has its own long and contested story, which this post is not going to settle, so read its absence from the rest of this as scope rather than a verdict.

NMN’s legal status is a mess. FDA ruled in November 2022 that it does not count as a dietary supplement, and trade reporting says two FDA letters dated September 29, 2025 reversed that. I have not confirmed those letters against FDA’s own text, so treat the status as unsettled.

Taurine is the most interesting fight in the field. Singh’s 2023 Science paper stretched the median mouse lifespan by 10 to 12 percent and reported that taurine in the blood falls with age in humans, monkeys and mice (32). That second claim is what created the product. An NIA-led group then found taurine flat or rising with age across three human groups plus primates and mice (33), and a separate group measuring 137 men aged 20 to 93 found no link between taurine and age, muscle, strength or how well muscle cells make energy (34). The mouse result stands unchallenged. The human claim underneath the marketing failed to repeat. Twice. No trial has tested taurine against a real human outcome. Anyone selling you certainty either way has not read all three papers.

Phosphatidylcholine earns its own answer, because the real story beats the marketing one. It is a fat molecule and one of the main ways we get choline from food, sold in pills for memory and cell health, and injected as a fat-dissolving product. Pill trials of phosphatidylcholine and lecithin have not helped memory in Alzheimer’s disease, the supporting work on lifespan sits in worms and mice, and no human trial measures anything that matters.

The case against it is better built than the case for it. Choline, phosphatidylcholine and carnitine feed gut bacteria that make a compound called trimethylamine, which the liver turns into TMAO. Tang followed 4,007 heart patients and found that high TMAO went with more heart attacks and strokes (35), building on Wang’s 2011 Nature paper showing that gut bacteria breaking down phosphatidylcholine drives artery disease in animals (36). Read that honestly and the research against phosphatidylcholine pills is stronger than the research for them. I would not take it. The injected version is worse. FDA warns about phosphatidylcholine and sodium deoxycholate products sold online as Aqualyx, Lipodissolve and Kabelline, and the only approved injection for fat reduction is deoxycholic acid on its own, for fat under the chin (37).

The money I would rather you did not spend

Injectable peptides bought online are the clearest line I draw. FDA put several, BPC-157 and epitalon among them, into category 2 of its bulk drug substances list in September 2023, which flags a real safety risk and blocks pharmacies from mixing them up for patients (38). There has been plenty of trade reporting that HHS moved to pull most of them back off that list. I have not confirmed any of it against FDA’s own text, so I am not going to tell you the rules changed. Coming off a restricted list would not be approval anyway. It never was.

I have seen videos online of people advocating injecting peptides, and it makes me uneasy.

Stem cell and exosome clinics have a legal record anyone can read. A federal court ruled against US Stem Cell Clinic in 2019, finding its product adulterated and misbranded, which are the legal terms for failing quality standards and being sold under a false label, and the reported harms include blindness. FDA states there is no approved exosome product for any medical use in this country (39). Young plasma got its own February 2019 FDA notice: no convincing evidence of benefit, against risks including fluid overload, TRALI, which is a serious lung injury, and catching an infection from the donor (40).

Growth hormone marketed for aging can put you in criminal court. 21 U.S.C. §333(e) makes it a federal felony to hand out hGH for anything other than an FDA-approved use in a diagnosed disease, and FDA counts writing the prescription as handing it out (41). It is the only drug in the code carrying that rule. The pitch still traces to Rudman’s 1990 NEJM paper: 21 men, six months, no placebo group, an 8.8 percent rise in lean body mass (42). Nobody counted deaths, and nobody was blinded. NEJM said in 2003 that consumers who meet those citations are being misled (43). Still doing sales work.

Consumer epigenetic age tests belong in the entertainment column. A 2025 preprint reports that running one sample twice can give answers as much as nine years apart on some clocks, and the reliability problem shows up in peer-reviewed work too (44). If your number moves three years after you start a supplement, you measured the test.

Full-body MRI in people with no symptoms is the expensive one. Scans turn up a confirmed cancer roughly 1.1 to 1.5 percent of the time, while about 95 percent of healthy adults show an incidental finding, meaning something the scan spots by accident, and around 91 percent of those turn out to mean nothing (45). Nine in ten. Nothing. What it reliably produces is a repeat MRI, a biopsy of something harmless, and months of fear. Skip it.

For patients, and for the clinicians reading over their shoulder

If you are a patient, work the list in the order the effect sizes come in. Blood pressure to target, which on my end means you own a cuff and bring me the readings, since I cannot take them from here. Quit smoking at any age, because the payoff is measured in years rather than percentage points. Build an aerobic base and lift something twice a week. Then, with whatever money and attention is left over, consider a supplement, and ask one question before you buy it: what did the trial actually measure? If the answer is a blood level, a clock or a marker, it did not measure your life. That question alone empties most of the aisle.

If you are a clinician, the awkward part of this field is that our best-evidenced longevity drugs are ones we already prescribe under other names. Blood pressure drugs, statins, GLP-1 receptor agonists, quit-smoking therapy. Patients arrive on video already carrying things they bought from direct-to-consumer platforms, so ask what they are taking without an eyebrow, because a patient who feels judged stops telling you. Get the compounded rapamycin, the peptide vial and the NMN into the chart and screen interactions properly. When you quote SELECT, quote the hierarchical testing failure along with it.

The Bottom Line

The gap between the best-proven ways to live longer and the most heavily marketed ones runs opposite to the ad money. Cardiorespiratory fitness, blood pressure control, and never picking up another cigarette sit at the top, with effects no capsule has come near.

GLP-1 receptor agonists have real outcome data and a real reason to use them. Metformin for longevity in people without diabetes rests on a weak comparison nobody randomized, plus two randomized trials showing it gets in the way of exercise. Rapamycin is interesting and unproven in humans. Senolytics have nothing at all. Aspirin in healthy older adults who had never had a heart attack made things measurably worse. NAD+ precursors move a blood level nobody has shown you should care about, the human claim behind taurine failed to repeat, and phosphatidylcholine has better research against it than for it.

Buy the used bike before you buy the peptide. If you want one thing to do this week, it does not cost anything.

Sources

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Large red EMERGENCY sign on the exterior of a hospital emergency department

Nurse Practitioners vs. Doctors in the ER: What the Research Actually Shows

On August 23, 2026August 30, 2026 By Dr. Scott RennieIn Healthcare System & TechnologyLeave a comment

A paper landed in the American Economic Review this month that is going to get quoted badly by almost everyone who quotes it. Physician groups will pull three numbers out of it. Nursing organizations will pull a different three. Both sets are in there, which is exactly why the paper is worth an hour of your attention instead of a headline.

David Chan and Yiqun Chen looked at 1.1 million emergency department visits across 44 Veterans Health Administration sites, involving 156 nurse practitioners and 1,348 physicians (1)(2). What makes it different from the usual scope-of-practice study is the design. VA provider schedules are set months in advance. Patients show up when they show up. That mismatch means the question of whether you got an NP or a physician on a given night was close to a coin flip rather than a reflection of how sick you looked, and it lets the authors claim causation instead of the correlation that plagues most of this literature.

What the numbers say

Patients seen by NPs had emergency stays 11 percent longer and cost about 7 percent more, roughly 66 dollars per visit (1)(3). Thirty-day preventable hospitalizations ran 20 percent higher. The AMA ran the arithmetic forward and estimated that routing a quarter of VA emergency patients to NPs adds about 129 million dollars a year net, after accounting for the salary difference between the two groups (3).

Thirty-day mortality showed no statistically significant difference (2).

Hold onto both of those. People are going to publish articles this fall that mention one and not the other.

The number everyone is going to skip

Here is the finding I think actually matters, and it is the one I expect to see least in the press coverage. It needs a slow walk, because it is the part that gets garbled every time.

Everything in the section above compares two averages. Add up all 156 NPs and take the mean. Do the same for the 1,348 physicians. Compare the two. Physicians win that comparison, and I am not waving that away.

Now throw the other profession out and look at physicians alone. We are not all the same. Some of us order a great deal of testing and some order very little. Look at length of stay instead, or at thirty-day bouncebacks, and the same wide scatter turns up. The NP group has an equally wide scatter inside it.

What Chan and Chen found is that the spread inside each profession is larger than the distance between the two averages. The gap between a low-resource physician and a high-resource physician is wider than the gap between the typical physician and the typical NP.

Put those two facts together and the distributions overlap most of the way. The strongest NPs sit well inside the physician range. The physicians at the expensive end sit well inside the NP range.

So the authors ran the obvious test. Pull one NP at random. Pull one physician at random. Compare what each of them actually did, and repeat that many times over. The NP is the better performer in 38 out of every 100 draws (1)(2).

That is not a rounding error, and the number is worth calibrating against the two ends it could have landed on. If the professions were genuinely separate tiers, with the weakest physician still ahead of the strongest NP, you would expect something near zero. If they were interchangeable you would expect 50. Thirty-eight sits far closer to interchangeable than to separate.

Two things it does not say. It does not say NPs are 38 percent as good. It does not say that 38 percent of NPs outperform physicians across the board. It describes random one-to-one matchups and nothing wider than that.

And physicians still take 62 of those 100 draws. The average difference did not evaporate. Both of those are true at the same time, and holding both at once is the whole trick with this paper.

The gap also moved around depending on what walked in the door. For the least complicated cases, the extra cost attached to NP care fell by roughly 80 percent compared with the average case (2). It narrowed further as NPs accumulated years, and narrowed again as they accumulated reps with a specific condition. Chan framed the takeaway as a question of “which patients they should see” rather than whether NPs should practice at all, and I think that is the honest reading of his own data.

The mechanism looks like uncertainty, not carelessness. NPs ordered more diagnostic testing and more specialist consults. For sepsis, stroke, and heart failure they were substantially more likely to admit. They wrote fewer opioid prescriptions and more antibiotic prescriptions (2). Read that list as a set and a pattern shows up: when the picture was ambiguous, the threshold to spend a resource dropped. Anyone who has been six months out of residency recognizes that behavior in themselves, because we all did it, and the thing that fixed it was not a different diploma but two thousand more patients.

An aside, because the word keeps getting misused. “Productivity” here is an economics term. It means outputs relative to inputs consumed, not effort expended and not how hard someone works. Nothing in this paper says NPs work less hard. It says a given clinical result cost more to produce.

Where I think it is weakest

One health system. One care setting. One hundred fifty-six NPs, against a national workforce of more than 461,000 licensed NPs (4)(5). The AANP’s objection that you cannot generalize from that sample to every emergency department in the country is fair, and I would make the same objection if the finding had gone the other way.

The VA population is also not America. Older, more male, more comorbidity, and enrolled in an integrated system with a shared record. The VA also grants full practice authority, which means these NPs were working without the collaborative arrangement most of my colleagues in private systems actually have. What the paper cannot see is the physician who glanced at a chart, said one sentence in passing, and quietly changed a plan. That interaction leaves no data trail and it happens constantly.

None of that makes the effect estimates wrong. It makes them local. An 11 percent length-of-stay difference in a VA emergency department is a measurement of that department, and treating it as a national verdict on a profession is a category error.

What this means for a virtual urgent care visit

Most of my work is telemedicine, so this is the setting I thought about first. Virtual urgent care now runs largely on nurse practitioners and physician assistants, and the mechanism Chan and Chen identified does not carry over to a video call cleanly. I cannot order a CBC in the middle of an encounter. I cannot walk anyone down the hall for imaging. When uncertainty rises the levers available are prescribe empirically or send the patient somewhere with hands, which happen to be the same two the study found NPs pulling more often (2).

There turned out to be more to say about that than belongs inside a piece about an economics paper. What the payment and rating structures do to the decision. Why recognizing the sick patient matters more in this setting than almost any other. What happens when the platform cannot order a test at all. I put all of it in its own article: Spotting the Sick One: The Only Decision That Really Matters in Virtual Urgent Care.

Virtual weight management is a different problem, and a more forgiving one.

Weight management is a different animal, and I think the gap mostly closes

Obesity medicine breaks almost every condition that produced the ED result. There is no undifferentiated chest pain arriving at 2 a.m. The diagnosis is usually made before the visit starts. Care is longitudinal, protocol-heavy, and forgiving of a decision revisited in four weeks. The study’s own results predict a smaller gap here, because it found the difference shrinking by about 80 percent on the least complex cases and shrinking again with condition-specific experience (2). An NP who has titrated a thousand patients through semaglutide dose escalation has more relevant pattern recognition than a physician who has titrated forty.

That said, the complexity in this field is real. It just shows up in different places than people expect. Sorting expected GLP-1 nausea from something needing imaging. Recognizing that a patient on 30 units of basal insulin and a sulfonylurea will need those doses coming down as the weight comes off, before the hypoglycemia arrives rather than after. Pancreatitis history. Family history of medullary thyroid carcinoma. Restrictive eating patterns that look like excellent adherence on a video call and are not. Secondary causes, and the long list of psychiatric medications that drive weight gain and never get revisited.

So the risk in virtual weight management is not the credential on the screen. It is the eight-minute refill visit, whoever is running it. A physician doing rushed protocol care and an NP doing thorough protocol care are not close, and I would put my patients with the second one.

The tell is what got asked. Did anyone go back through the medication list once the weight started coming off, or was the box checked and the refill sent? Did anyone ask what the patient is actually eating on the days the nausea is bad, which is the question that separates a tolerable side effect from six weeks of accidental starvation. Nothing on that list has a degree attached to it. It has time attached to it, and time is a scheduling decision made by somebody in an office who has never met the patient.

For patients

You are allowed to ask who you are seeing and what their background is, and no reasonable clinician will be offended. What you should not do is treat the letters after the name as the whole answer. This study says a randomly chosen NP outperforms a randomly chosen physician 38 times out of 100. Experience with your specific problem is the more useful question. If you are starting a GLP-1, ask how many patients they have managed on it. If you are calling a virtual urgent care with chest pain or a severe headache, understand that any competent clinician in that setting is going to send you somewhere with a CT scanner, and that is the correct answer rather than a failure of the visit.

For clinicians

Two things I would take into practice from this paper. First, the within-profession spread being wider than the between-profession spread should change how we think about quality improvement. We spend enormous political energy on scope-of-practice fights and almost none on identifying and coaching the outliers inside our own group, and the data says the second one has more room in it.

Second, the actionable finding for anyone designing care is the complexity gradient rather than the average effect. Straightforward cases should route broadly. Diagnostic ambiguity and high-acuity complaints should route to whoever has the most reps with them, assigned on individual performance data rather than on license class. That is a solvable engineering problem and almost nobody is solving it.

The Bottom Line

This is a serious paper with a genuinely strong design, and its central finding is not the one being headlined. Physicians came out ahead on average in a VA emergency department. NPs came out ahead in 38 percent of head-to-head matchups, the difference nearly disappeared on straightforward cases, and thirty-day mortality was a wash. The spread inside each profession was wider than the gap between them, which is the part worth carrying around.

For virtual weight management I expect the gap to be small, and I care far more about how much time the visit gets and how deep the protocol runs than about which degree is on the screen.

Match the case to the clinician. That is the finding.

Sources

Chan DC Jr, Chen Y. The Productivity of Professions: Evidence from the Emergency Department. American Economic Review, August 2026. https://www.aeaweb.org/articles?id=10.1257/aer.20241007
Berkeley Research. New study upends traditional thinking about doctors versus nurse practitioners. August 22, 2026. https://vcresearch.berkeley.edu/news/new-study-upends-traditional-thinking-about-doctors-versus-nurse-practitioners
American Medical Association. Nurse practitioners’ care linked to 11% longer stays in the ED. https://www.ama-assn.org/practice-management/scope-practice/nurse-practitioners-care-linked-11-longer-stays-ed
Clinician.com. Organizations Take Issue with Data Regarding Nurse Practitioner Care in the ED. https://www.clinician.com/articles/organizations-take-issue-with-data-regarding-nurse-practitioner-care-in-the-ed
American Association of Nurse Practitioners. Nurse Practitioners in Primary Care (2025 NP count). https://www.aanp.org/advocacy/advocacy-resource/position-statements/nurse-practitioners-in-primary-care
Chan DC Jr, Chen Y. The Productivity of Professions: Evidence from the Emergency Department. NBER Working Paper No. 30608, issued October 2022, revised August 2026. https://www.nber.org/papers/w30608

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

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 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 velvet patch on the back of the neck

Skin tags carry information

What high glucose actually does to a wound

The infections that come with the territory

Hidradenitis suppurativa, and what changed

The foot

What I ask for on video

For patients

For colleagues

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 actually works, and it is not a close call

Nobody ever counted to ten thousand

The interventions with no sales force

Weight loss, and what SELECT actually settled

The prescriptions people ask me for by name

The supplement aisle, and phosphatidylcholine in particular

The money I would rather you did not spend

For patients, and for the clinicians reading over their shoulder

The Bottom Line

Related Reading

Sources

What the numbers say

The number everyone is going to skip

Where I think it is weakest

What this means for a virtual urgent care visit

Weight management is a different animal, and I think the gap mostly closes

For patients

For clinicians