Do GLP-1s cause muscle loss? What the research shows

Yes, some of the weight lost on a GLP-1 is muscle, not fat. In the body composition substudies of the two largest trials, STEP 1 for semaglutide and SURMOUNT-1 for tirzepatide, roughly a quarter to just under half of the total weight lost was lean mass rather than fat. That sounds alarming, and the headlines have treated it that way. The fuller picture is more reassuring, and the part that matters most is the part a patient can do something about.

This article covers how much of GLP-1 weight loss is muscle, why it happens, whether it is a problem worth worrying about, and what protects lean mass during treatment. It is written for patients on or considering a GLP-1 who have seen the muscle-loss headlines and want to know what the evidence says.

How much of the weight is muscle

The clearest data comes from the DXA body composition substudies built into the registration trials. In the STEP 1 substudy of semaglutide (published in the New England Journal of Medicine in 2021), lean mass accounted for about 40 to 45 percent of the total weight lost. In the SURMOUNT-1 substudy of tirzepatide (published in the New England Journal of Medicine in 2022), the figure was lower, roughly a quarter to a third.

These were large trials using DXA imaging to measure body composition directly, so the findings are well established. A patient losing 15 percent of their body weight on semaglutide is losing fat and muscle at the same time, and the muscle portion is not trivial.

Older GLP-1s show the same pattern. Liraglutide has been associated with lean mass making up as much as 60 percent of weight lost in some analyses. The effect is a feature of the whole medication class, not one drug.

Why it happens

This is not something the medication does to muscle directly. It is what happens whenever the body loses weight quickly, by any method. When you take in less energy than you burn, the body draws on both fat and lean tissue to make up the difference. Rapid weight loss, whether from surgery, a very low calorie diet, or a GLP-1, always takes some muscle with the fat.

GLP-1s produce more weight loss than diet and lifestyle changes alone, so the absolute amount of muscle lost is larger simply because the total loss is larger. The ratio of muscle to fat is roughly what you would expect for the amount of weight involved. The mechanism is ordinary. The scale is what is new.

Whether it is a problem

Here the honest answer complicates the headline. In both STEP 1 and SURMOUNT-1, the proportion of lean mass relative to total body mass still improved. Patients ended treatment with a better body composition than they started with, because they lost proportionally more fat than muscle. The SEMALEAN study, a 2025 observational study that tracked patients over a year, found that lean mass dropped early but then stabilised, handgrip strength improved, and the prevalence of sarcopenic obesity fell from 49 percent at baseline to 33 percent.

So for most patients, some lean mass loss during active weight loss is a normal part of getting smaller, and overall muscle function can improve rather than decline. The concern is sharper for two groups. Older adults are already losing muscle with age, and anyone starting treatment with low muscle mass has less to spare. For them, losing more lean tissue on top of an existing decline is a real clinical risk worth managing deliberately.

What protects muscle

Two things preserve lean mass during weight loss, and they work together. The first is adequate protein. A 2024 systematic review and meta-analysis found that a protein intake of 1.2 to 1.6 grams per kilogram of body weight per day preserves lean mass during weight loss, well above the standard dietary recommendation of 0.8 grams, because a body in an energy deficit needs more protein to hold onto muscle. The practical problem on a GLP-1 is that the medication suppresses appetite, which makes hitting a protein target harder exactly when it matters most. Anchoring every meal around a protein source, rather than trying to eat more overall, is the workable approach.

The second is resistance training. Lifting, in the broad sense, preserves lean mass during a calorie deficit far better than aerobic exercise or walking alone. A pooled analysis of older adults on calorie-restricted diets found that resistance training preserved nearly all lean mass. In a 2025 published case series, patients who combined a GLP-1 with structured resistance training three to five times a week preserved noticeably more lean mass, and some gained lean tissue while losing between 13 and 33 percent of their body weight.

Resistance training does not require a gym. Bodyweight movements, resistance bands, and a few dumbbells produce the muscle-preserving signal at the level most patients on a GLP-1 need. What matters is that the muscle is asked to work against resistance regularly, so the body has a reason to keep it.

This is the practical heart of it. Muscle loss on a GLP-1 is not a reason to avoid treatment. It is a reason to treat protein and strength work as part of the treatment, not an optional extra. The medication handles appetite and fat loss. Protecting muscle is the work that sits alongside it, and it is work that reliably pays off.

For more on the wider treatment picture, see our companion articles on what GLP-1 treatment costs in South Africa and coming off GLP-1 medication without losing the result.

References

1. Wilding, J.P.H., Batterham, R.L., Calanna, S., et al. (2021) 'Once-weekly semaglutide in adults with overweight or obesity (STEP 1)', New England Journal of Medicine, 384(11), pp. 989-1002.
2. Jastreboff, A.M., Aronne, L.J., Ahmad, N.N., et al. (2022) 'Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1)', New England Journal of Medicine, 387(3), pp. 205-216.
3. Linge, J., Birkenfeld, A.L. and Neeland, I.J. (2024) 'Muscle mass and glucagon-like peptide-1 receptor agonists: adaptive or maladaptive response to weight loss?', Circulation, 150(16), pp. 1288-1298.
4. Alissou, M., Demangeat, T., Folope, V., et al. (2025) 'Impact of semaglutide on fat mass, lean mass and muscle function in patients with obesity: the SEMALEAN study', Diabetes, Obesity and Metabolism, 28(1), pp. 112-121.
5. Tinsley, G.M. and Nadolsky, S. (2025) 'Preservation of lean soft tissue during weight loss induced by GLP-1 and GLP-1/GIP receptor agonists: a case series', SAGE Open Medical Case Reports, 13.
6. 'Enhanced protein intake on maintaining muscle mass, strength, and physical function in adults with overweight or obesity: a systematic review and meta-analysis' (2024), Clinical Nutrition ESPEN.