Tag: Sarcopenia

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

Doctor Supervised Weight Loss: What Works Long Term

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

Telling patients to eat less and move more doesn’t cut it. Obesity is a chronic disease, and progress requires structured, ongoing, individualized care. The hardest part clinically is making sure the weight that comes off is fat rather than muscle.

Losing muscle costs more than strength. It costs independence, recovery capacity, and eventually survival. Older adults and patients with low baseline activity are the most exposed. Poorly managed weight loss produces sarcopenia, the loss of muscle mass and function. Layer excess fat on top and you get sarcopenic obesity, where a patient looks heavy and is functionally weak and metabolically compromised at the same time.

The European Working Group on Sarcopenia in Older People sets out how to catch it early. It starts with loss of strength, measured by grip strength or a chair-stand test. DXA or BIA can confirm low muscle mass. Poor strength plus low mass plus reduced physical performance defines severe sarcopenia. These definitions give us a framework to act before decline becomes permanent (Cruz-Jentoft et al., Age Ageing, 2019).

Muscle mass predicts survival on its own. Appendicular Lean Mass Index, lean tissue in the arms and legs divided by height squared, is a reliable measure, and people in the top quartile carry substantially lower all-cause mortality than those in the lowest, even after adjusting for BMI and comorbidities (Srikanthan & Karlamangla, Am J Med, 2014). Put plainly, a patient with stronger arms and legs has better odds of living longer regardless of what the scale says.

Strength testing matters as much as mass. Low grip strength tracks with higher mortality from cardiovascular disease, cancer, and respiratory illness. Poor lower-body strength, showing up as slower gait speed or difficulty rising from a chair, tracks with frailty, hospitalization, and long-term disability.

Both measures are cheap and fast, and both are underused. Grip strength needs a dynamometer and a hand to put it in, which rules it out of any remote encounter. The 30-second sit-to-stand doesn’t. A hard chair, arms crossed over the chest, as many stands as the patient can complete in thirty seconds, counted by whoever is watching. It works over video as well as it works in a room, and it yields a number worth tracking across visits. One usable functional measure beats a chart full of weights.

Nutrition is the cornerstone of preserving muscle during weight loss. The baseline protein RDA of 0.8 g/kg/day is inadequate for many adults, particularly older patients and anyone in a calorie deficit. The evidence supports closer to 1.2 to 1.6 g/kg/day, and up to 2.0 g/kg/day in some medically supervised cases (Paddon-Jones et al., Am J Clin Nutr, 2015; Bauer et al., J Am Med Dir Assoc, 2013). Spacing intake across meals rather than loading it at dinner sustains muscle protein synthesis better. Whey and casein, soy, eggs, and blended plant sources all work.

Calculating a target in patients with obesity is genuinely awkward. Actual body weight overshoots. Ideal body weight undershoots. Adjusted body weight is the usual compromise, and reasonable clinicians disagree about which to use. For a 5’6″ patient, a target weight around 73 kg at 1.5 g/kg puts the daily goal near 110 grams, which is a number a patient can actually work with.

Exercise has to include both resistance and aerobic work. Resistance training protects and builds lean mass. Aerobic activity improves cardiovascular and metabolic health. A 2022 systematic review and meta-analysis found the combination conferred the greatest mortality risk reduction, and notably found that weight training alone wasn’t associated with lower mortality among people doing no aerobic exercise (Shailendra et al., Am J Prev Med, 2022). For a patient that translates to brisk walking or cycling most days plus two or three weekly strength sessions using bands, weights, or bodyweight.

Think of muscle like a retirement account. Build it and hold it early, so it is there when it is needed. A patient in their seventies who lands in the hospital with pneumonia can lose a large fraction of their reserve to a few days of immobility and poor intake. If the reserve was thin going in, the decline may be permanent, and it shows up later as falls, fractures, and lost independence. Investing ahead of time changes that trajectory.

Medication is a real adjunct, and it has to be paired with strategies that protect lean tissue. GLP-1 receptor agonists produce substantial weight loss, and a meaningful fraction of that loss is lean mass. Adequate protein and resistance training are the mitigation strategies with actual evidence behind them, and body composition deserves monitoring wherever it is available rather than weight alone.

As clinicians, we need to screen past BMI. Ask about physical activity. Get a functional measure. Consider dietary adequacy. Refer to dietitians, physical therapists, or trainers where it helps, and even a single session with a trainer improves safety and confidence with resistance work. Set goals patients can hold: one to two pounds a week of fat loss while protecting muscle.

Obesity treatment is chronic care. The point is helping patients hold strength, mobility, and independence while metabolic health improves, and preserving muscle sits at the center of that.

Scott Rennie, D.O.

References:

1. Cruz-Jentoft AJ, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16-31. https://pubmed.ncbi.nlm.nih.gov/30312372/

2. Srikanthan P, Karlamangla AS. Muscle mass index as a predictor of longevity in older adults. Am J Med. 2014;127(6):547-553. https://pubmed.ncbi.nlm.nih.gov/24561114/

3. Paddon-Jones D, et al. Protein and healthy aging. Am J Clin Nutr. 2015;101(6):1339S-1345S. https://pubmed.ncbi.nlm.nih.gov/25926511/

4. Bauer J, et al. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. J Am Med Dir Assoc. 2013;14(8):542-559. https://pubmed.ncbi.nlm.nih.gov/23867520/

5. Shailendra P, et al. Resistance Training and Mortality Risk: A Systematic Review and Meta-Analysis. Am J Prev Med. 2022;63(2):277-285. https://pubmed.ncbi.nlm.nih.gov/35599175/

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.