Tag: GLP-1

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

On 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.

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

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  33. Santos-Dias A, et al. Taurine concentrations in humans and nonhuman primates do not decline with age. Science. 2025;388(6751). https://doi.org/10.1126/science.adl2116
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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 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.

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

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
Man holding dumbbell and protein shake on mountain with rising fitness progress chart

Do Ozempic and Zepbound Cause Muscle Loss?

On By Dr. Scott RennieIn Weight Loss & Metabolic Health1 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.

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:

GLP-1 Therapies in 2026: Beyond Blood Sugar and the Scale, AJMC: https://www.ajmc.com/view/glp-1-therapies-in-2026-beyond-blood-sugar-and-the-scale

Should We Be Concerned About Muscle Loss With GLP-1s?, Medscape: https://www.medscape.com/viewarticle/should-we-be-concerned-about-muscle-loss-glp-1s-2026a1000p67

Increasing GLP-1 Use Raises Muscle Loss Concerns, Medscape: https://www.medscape.com/viewarticle/increasing-glp-1-use-raises-muscle-loss-concerns-2026a1000p4h

Deep Dive: GLP-1, Muscle Loss and What It Means, Medscape: https://www.medscape.com/c99/p10/are-concerns-glp-1s-and-muscle-loss-real-or-overblown-2026a1000gdz

New GLP-1 Therapies Enhance Quality of Weight Loss by Improving Muscle Preservation, American Diabetes Association: https://diabetes.org/newsroom/press-releases/new-glp-1-therapies-enhance-quality-weight-loss-improving-muscle-0

Drug enhances muscle repair during GLP-1 weight-loss treatment in mice, Stanford Medicine: https://med.stanford.edu/news/all-news/2026/06/muscle-glp-1.html

Retatrutide FDA Approval Status 2026, freemedicaljournals.com: https://freemedicaljournals.com/blog/retatrutide-fda-approval-status-2026/

Results From Amgen’s Phase 2 Obesity Study of Monthly MariTide, Amgen: https://www.amgen.com/newsroom/press-releases/2025/06/results-from-amgens-phase-2-obesity-study-of-monthly-maritide-presented-at-the-american-diabetes-association-85th-scientific-sessions

Spiral staircase with glowing blue arrow indicating growth percentages of +15%, +35%, +58%, +60%, culminating at 100%.

Wegovy 7.2 mg: Who Should Consider the Higher Dose?

On By Dr. Scott RennieIn Weight Loss & Metabolic Health1 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.

One safety finding from STEP UP deserves more attention than it got. Dysesthesia, meaning abnormal skin sensation, was reported by 22.9 percent of patients on 7.2 mg against 6.0 percent on 2.4 mg and 0.5 percent on placebo. I go through what that means and how to counsel for it in my article on GLP-1 skin and nerve pain.

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

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

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

Sources:

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

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

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

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

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

On By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

For years, if you asked me “is there a pill version of these weight-loss drugs?”, the honest answer was no, not really. That changed twice in the past eight months. If you haven’t been following the news closely, the options today look very different than they did just a year ago.

A quick note on names first, since patients ask me this a lot. The Lilly drug some people have heard called “Fonday-o” is actually called orforglipron. Its brand name is official now, not a guess. The FDA approved it on April 1, 2026, under the brand name Foundayo. Before that, on December 22, 2025, the FDA approved a 25 mg oral semaglutide tablet under the Wegovy name. GLP-1 medicines help control appetite and blood sugar, and this was the first pill version of one approved for long-term weight management. Both pills are real, both are approved, and both can be prescribed today.

Why the two pills work so differently in your body

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

Novo Nordisk’s solution was to add an ingredient called SNAC that helps the drug get absorbed before your stomach destroys it. According to a review in the medical journal Clinical Diabetes, SNAC does three things at once. It changes the local acidity around the tablet as it dissolves, it briefly protects the drug from a stomach enzyme called pepsin that would otherwise break it down, and it helps the drug pass through the stomach lining into your bloodstream. This absorption happens in the stomach itself, not the intestines, which is unusual for a pill. The drug essentially enters your body right where the tablet is sitting against your stomach wall.

That clever trick comes with a catch. You have to take oral semaglutide on an empty stomach with no more than about four ounces of plain water, and you can’t eat or drink anything else, including coffee or other medications like thyroid pills, for at least 30 minutes afterward. Taking it too close to breakfast or your other pills can reduce how much of the drug actually gets into your system. This isn’t a small detail. It can be the difference between the medicine working well and not working at all.

Orforglipron works completely differently. It’s what’s called a small molecule, meaning it’s a simple, stable chemical rather than a fragile peptide chain. It belongs to the same family of drugs as semaglutide. GLP-1 receptor agonists mimic a natural gut hormone that reduces appetite, and because orforglipron has no peptide to protect, it doesn’t need any special absorption booster and doesn’t come with a strict timing routine. Lilly describes it as the only GLP-1 weight-loss pill you can take at any time of day, with or without food or water. In real life, that means someone who works night shifts, or who already takes six other pills each morning, doesn’t need a complicated schedule to make it work.

What the study results actually show

Here’s where I want you to slow down before drawing conclusions, because it’s easy to misread these numbers.

In a 64-week study called OASIS 4, which tested the drug in 307 adults with obesity or being overweight who did not have diabetes, oral semaglutide 25 mg led to about 17% average weight loss in people who stayed on the medicine the whole time, compared with about 3% for those taking a placebo (an inactive pill used for comparison). When you count everyone in the study, including people who stopped early, the numbers were about 14% versus 2%. Seventy-six percent of people lost at least 5% of their body weight, compared with 31% on placebo.

In a separate study called ATTAIN-1, published in the New England Journal of Medicine, orforglipron was tested at three different doses (low, medium, and high) over 72 weeks. Average weight loss was 7.8%, 9.3%, and 12.4% at those doses, compared with 2.1% on placebo. At the highest dose tested in the trial, 36% of people lost 15% or more of their body weight, and 18.4% lost 20% or more, compared with 5.9% and 2.8% on placebo.

If you compare those numbers side by side, it looks like semaglutide wins, and I don’t think that comparison holds up. These are two separate studies, different patients, different lengths of time, different ways of measuring results, and nobody has run them head-to-head in the same people at the same time. What I can say confidently is that both pills produce weight loss that’s meaningful and far beyond anything we had in pill form before 2025.

One more detail worth knowing, because it can be confusing if you read news coverage of the studies. The doses of Foundayo that actually got approved are 0.8, 2.5, 5.5, 9, 14.5, and 17.2 mg, and your doctor increases your dose gradually, about every 30 days. Those numbers are different from the 6, 12, and 36 mg doses mentioned in the New England Journal of Medicine study. That’s because the trial used a different capsule formula than the one that ended up on the market. The 17.2 mg tablet you can actually get prescribed is equivalent to the 36 mg dose used in the trial. So if you notice your maximum dose sounds much smaller than what you saw in the news, that’s why.

Side effects

Both drugs work in a similar way in the body, and both come with similar side effects: nausea, vomiting, diarrhea, and constipation.

The ATTAIN-1 study reported specific numbers for orforglipron. Nausea occurred in 28.9% to 35.9% of people across the different doses, compared with 10.4% on placebo. Constipation occurred in 21.7% to 29.8%, versus 9.3% on placebo. Vomiting occurred in 13.0% to 24.0%, versus 3.5% on placebo. The number of people who stopped taking the drug because of side effects went up with higher doses, from 5.3% at the lowest dose to 10.3% at the highest, compared with 2.7% on placebo. Most side effects were mild to moderate.

Novo Nordisk reported that oral semaglutide’s side effects looked similar to what we already know from the injectable version of semaglutide, including the same warnings about pancreas inflammation, gallbladder problems, and allergic reactions. If you’ve taken injectable semaglutide before, this side effect pattern will likely feel familiar.

How I think about choosing between them

If you’re already doing well on injectable semaglutide and want to get away from needles, the oral tablet is the more natural next step. It’s the same active medicine, has a familiar side effect pattern, and carries the same approved benefit for heart health in people with existing heart disease.

If your biggest obstacle is fitting a medicine into a busy or unpredictable schedule, orforglipron tends to be more forgiving. That 30-minute waiting period for oral semaglutide sounds minor when we talk it through on a video visit, but in real life it trips people up. I’ve seen patients struggle with oral semaglutide not because it didn’t work, but because busy weekday mornings made it hard to follow the timing rules.

Cost is the third thing to consider, and it’s changing quickly. Novo Nordisk launched the 1.5 mg starting dose at $149 per month, with savings programs available. Lilly is offering self-pay pricing through its LillyDirect program, with commercially insured patients paying as little as $25 per month, and some Medicare Part D patients paying $50 starting as soon as July 1, 2026. These programs get updated often, so it’s worth checking the current terms before assuming a specific price applies to you. I haven’t run into a prior-authorization fight or a stocking problem with Foundayo yet. Most of what I prescribe goes through LillyDirect, cash pay, because it’s one of the cheaper options on the table. Patients who have insurance coverage tend to ask for injectable Wegovy or Zepbound instead.

We finally have two pill options, and each one tends to fail for a different reason, whether that’s the timing rules or something else. Figuring out which failure point matters most for your life is really the key to choosing the right one.

Scott Rennie, D.O.

Sources

FDA approves Novo Nordisk’s Wegovy pill, the first and only oral GLP-1 for weight loss in adults (PR Newswire): https://www.prnewswire.com/news-releases/fda-approves-novo-nordisks-wegovy-pill-the-first-and-only-oral-glp-1-for-weight-loss-in-adults-302648344.html
FDA Approves Oral Semaglutide as First GLP-1 Pill for Weight Loss (AJMC): https://www.ajmc.com/view/fda-approves-oral-semaglutide-as-first-glp-1-pill-for-weight-loss
Current Understanding of SNAC as an Absorption Enhancer: The Oral Semaglutide Experience (Clinical Diabetes, ADA): https://diabetesjournals.org/clinical/article/42/1/74/153538/Current-Understanding-of-Sodium-N-8-2
FDA approves Lilly’s Foundayo (orforglipron) (Eli Lilly investor release): https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-foundayotm-orforglipron-only-glp-1-pill
FDA Approves First New Molecular Entity Under National Priority Voucher Program (FDA): https://www.fda.gov/news-events/press-announcements/fda-approves-first-new-molecular-entity-under-national-priority-voucher-program
Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment (New England Journal of Medicine, ATTAIN-1): https://www.nejm.org/doi/full/10.1056/NEJMoa2511774
Complete ATTAIN-1 results published in NEJM (Eli Lilly): https://lilly.gcs-web.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-demonstrated-meaningful-weight
FOUNDAYO (orforglipron) tablets, US prescribing information (FDA): https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/220934Orig1s000lbl.pdf
Approved dosing for Foundayo for weight management (Lilly Medical): https://medical.lilly.com/us/products/answers/what-is-the-approved-dosing-for-foundayo-orforglipron-for-weight-management-320858
Foundayo now available in the U.S. (Eli Lilly investor release): https://investor.lilly.com/news-releases/news-release-details/foundayotm-orforglipron-lillys-new-oral-glp-1-pill-weight-loss

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.

Can You Do Intermittent Fasting on Ozempic or Wegovy?

On By Dr. Scott RennieIn Weight Loss & Metabolic HealthLeave a comment

Weight comes up in almost every visit I do. For some patients it is fifteen pounds standing between them and a better blood pressure number. For others it is obesity that has already done damage, and the conversation starts further back. The work can feel overwhelming from the inside. What’s changed is that the tools finally match the size of the problem. Medications like Ozempic, Wegovy, Mounjaro, and Zepbound, the GLP-1 receptor agonists, have shifted how this is approached, and paired with a structure like intermittent fasting they help people lose weight and keep it off.

What GLP-1 Agonists Do

These drugs mimic glucagon-like peptide-1, a hormone that regulates appetite and blood sugar. Given as medication, they slow gastric emptying and push stronger satiety signals to the brain, so fullness arrives earlier and stays longer. They also improve insulin sensitivity, which is why they earned their place in type 2 diabetes first.

The weight effect is substantial. Wegovy and Zepbound carry FDA approval specifically for weight loss. Ozempic and Mounjaro are approved for diabetes and produce strong weight results as well, which is the source of most of the confusion patients arrive with about which drug is which.

How They Work With Intermittent Fasting

Intermittent fasting improves insulin sensitivity, supports fat loss, and helps regulate hunger hormones. Staying with it is the hard part. Many patients tell me they can’t get past the hunger. GLP-1 medications change that equation by blunting appetite and cravings, which makes a fasting schedule something a person can actually hold.

A patient of mine started a 16:8 fasting plan (16 hours fasting, 8 hours eating) while on a GLP-1 medication. Before starting the medication, she felt shaky and irritable during fasting. After starting, she was surprised by how manageable it felt. She ate smaller meals, felt full, and didn’t struggle to maintain the fasting window.

Side Effects and Adjustments

Nausea leads the list, and it’s worst early. Diarrhea and reflux show up too. Most of it settles as the body adapts. Start low, titrate slowly, and resist the urge to chase the next dose because the scale stalled for two weeks. Patients who stay in contact through the titration get their dose adjusted before they quit over side effects, and the ones who go quiet are the ones who stop the drug entirely.

Barriers to Access

Getting these medications is its own project. Cost is the main wall. Insurance coverage for weight loss remains inconsistent in a way that’s hard to explain to a patient who has just been told the drug would help, and out-of-pocket pricing is punishing. Demand has outrun supply, so delays and shortages are part of the picture.

Then there are the compounded versions. Some pharmacies sell them well below brand pricing, and they’re not FDA-approved. Safety and potency can’t be guaranteed. I tell patients to stay away from them, and I don’t soften that advice when someone pushes back on price.

Putting It Into Context

These aren’t quick fixes. They are tools, and they work when they sit on top of durable changes: balanced eating, regular activity, attention to mental health. Intermittent fasting is one workable way to structure eating alongside them. The lifestyle piece doesn’t become optional because a medication is doing part of the lifting.

When patients pair the medication with habits they can sustain, results hold longer and vary less. The goal is a set of strategies that still works three years from now, not the fastest possible drop on the scale.

Scott Rennie, D.O.

Sources

U.S. Food and Drug Administration. FDA Approvals: Wegovy, Zepbound.

Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384:989-1002.

Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387:205-216.

American Diabetes Association. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes, 2024. Diabetes Care. 2024;47(Suppl 1):S181-S202.

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.