Most of the kilograms lost on semaglutide are body fat, and in the trials muscle strength did not fall but rose. In a 2026 meta-analysis, lean mass made up on average 35.2 percent of the weight lost on semaglutide, and the rest was fat. In the SEMALEAN study, handgrip strength rose by 4.5 kg after a year. Below we show what the studies measured and what helps protect muscle during treatment.
Why do you also lose lean mass when losing weight?
With any larger weight loss the body loses some lean mass alongside fat. This applies to diet, exercise, bariatric surgery and medicines. Lean mass is not only muscle: it also includes water, internal organs and connective tissue.
DXA, a low-dose whole-body X-ray scan, does not separate muscle from the other parts of this mass. A loss of lean mass in a study therefore does not mean the same loss of muscle. Magnetic resonance imaging measures muscle more precisely, and we describe its results below.
How much of the weight lost is fat?
According to a meta-analysis of 20 trials with 15,782 participants, lean mass made up 25 to 39 percent of the weight lost with medicines of this group. The work was published in March 2026 in Diabetes, Obesity and Metabolism. It compared the medicines with lifestyle changes alone.
| Way of losing weight | Share of lean mass in the weight lost |
|---|---|
| Semaglutide | 35.2 percent |
| Tirzepatide | 25.4 percent |
| Liraglutide | 26.8 percent |
| Diet and exercise | 26.2 percent |
| Diet and exercise with strength training | 17.5 percent |
According to the authors, the share of lean mass with the medicines was close to that with diet and exercise alone. The combination with strength training did best. Fat was therefore lost clearly faster than lean mass.
What did the SEMALEAN study show?
SEMALEAN looked not only at body composition but also at muscle strength. It included 115 people with obesity treated with semaglutide 2.4 mg for a year, and 106 completed follow-up. The average BMI was 46.3, so this was a group with very severe obesity.
| SEMALEAN | After 7 months | After 12 months |
|---|---|---|
| Weight loss | 10 percent | 13 percent |
| Fat loss | 14 percent | 18 percent |
| Lean mass | down by 3 kg | no further fall |
| Handgrip strength | not reported | up by 4.5 kg |
Lean mass fell during the first seven months and then stabilised. Handgrip strength rose after a year. The share of people with sarcopenic obesity, meaning obesity combined with weak muscles, fell from 49 to 33 percent.
Who loses the most fat?
In SEMALEAN women lost the most weight and fat. Weaker effects were seen in people with type 2 diabetes and in people who had used a GLP-1 medicine before. The clearest changes in body composition were seen in people who had had bariatric surgery.
The study also measured resting metabolism. Expressed per kilogram of lean mass, it rose between the seventh and twelfth month. The authors write that semaglutide 2.4 mg preserved lean mass and metabolic efficiency while improving muscle function.
What did MRI of the thigh muscles show?
Magnetic resonance imaging showed that semaglutide reduced not only body fat but also the fat inside the muscles. These results come from an analysis of 55 participants of STEP UP, published in September 2026. Most of them received 7.2 mg of semaglutide for 72 weeks.
- Body fat: 11.1 litres less than on placebo.
- Visceral fat: 1.5 litres less than on placebo.
- Fat in the thigh muscles: 0.92 percentage points less than on placebo.
- Thigh muscle volume: 1.1 litres less, without a significant difference from placebo.
Physical function measured by the number of chair stands in 30 seconds did not get worse. In the semaglutide group and in the placebo group it averaged 13 repetitions at the start and 15 repetitions after 72 weeks. The authors write that the effect of weight loss on muscle structure and function needs further research.
Why do study results differ so much?
A review of six studies with 1541 participants, published in 2024, showed a wide spread of results. The share of lean mass in the weight lost ranged from almost zero to 40 percent. Larger losses were seen more often in larger trials.
Several things affect the result at once. The first is the method of measurement, because DXA counts all lean mass and MRI only muscle. The second is the group studied, for example the very severe obesity in SEMALEAN. The third is whether participants trained and how much protein they ate. The review's overall conclusion was still favourable: the share of lean mass in the whole body rose after treatment.
How to protect muscle during treatment?
Strength training proved the strongest way to protect muscle in the studies. In the 2026 meta-analysis, diet and exercise with strength training limited the share of lean mass in the weight lost to 17.5 percent. The authors name three things that help keep muscle during a large weight loss.
- Strength training: gave the most favourable composition of the weight lost of all the approaches compared.
- Enough protein: the authors name it alongside training as a basis for protecting muscle.
- Measuring body composition: shows whether you are losing fat, not just kilograms.
With a smaller appetite it is especially worth watching the amount of protein in your meals. How to measure body composition and fitness is described in the guide on how to measure peptide results.
Does semaglutide do worse than tirzepatide?
In the 2026 meta-analysis the share of lean mass was higher with semaglutide than with tirzepatide, 35.2 against 25.4 percent. The comparison comes, however, from different trials, not from a direct head-to-head comparison. The trials differed in their groups, duration and method of measurement.
The details of tirzepatide's effect on muscle are described in a separate guide in this series. A comparison of the weight results alone is in the guide semaglutide vs tirzepatide vs retatrutide.
Where to buy semaglutide?
The shop offers semaglutide 3 mg Bio-Peptide for 90 EUR, in stock. All information about the molecule is on the semaglutide page. The course of weight loss over the months is described in the guide on semaglutide results.
The products in the shop are material for laboratory research, not the medicines Wegovy or Ozempic. Decisions about treating obesity are made by a doctor. The difference is explained in the guide on why semaglutide and tirzepatide are prescription-only.
Frequently asked questions
Does semaglutide burn muscle?
Part of the weight lost is lean mass, on average 35.2 percent according to a 2026 meta-analysis. Most of the loss is fat, and in SEMALEAN handgrip strength rose by 4.5 kg after a year.
How much fat do you lose on semaglutide?
In SEMALEAN body fat fell by 18 percent after 12 months with a 13 percent fall in body weight.
How to keep muscle on semaglutide?
Strength training did best, limiting the share of lean mass in the weight lost to 17.5 percent. The authors of the meta-analysis also name enough protein and measuring body composition.
Does semaglutide weaken physical fitness?
In the STEP UP analysis the number of chair stands in 30 seconds rose on average from 13 to 15, the same as on placebo. In SEMALEAN handgrip strength rose after a year.
Is lean mass the same as muscle?
No, it also includes water, organs and connective tissue. DXA does not separate muscle from these parts; magnetic resonance imaging does this more precisely.
Sources
- Eisa N, Barood O. Lean Mass Changes With Incretin Therapy Versus Lifestyle Intervention: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. Diabetes, Obesity and Metabolism, 2026, 28(6): 4818-4827. https://doi.org/10.1111/dom.70666
- Alissou M, Demangeat T, Folope V et al. Impact of Semaglutide on fat mass, lean mass and muscle function in patients with obesity: The SEMALEAN study. Diabetes, Obesity and Metabolism, 2026, 28(1): 112-121. https://doi.org/10.1111/dom.70141
- Hjelmesæth J, Bhat S, Garvey WT et al. Effect of Semaglutide on Thigh Skeletal Muscle Volume, Fat Infiltration and Physical Function in People With Obesity: Secondary Analysis of STEP UP. Diabetes, Obesity and Metabolism, 2026. https://doi.org/10.1111/dom.71323
- Bikou A, Dermiki-Gkana F, Penteris M et al. A systematic review of the effect of semaglutide on lean mass: insights from clinical trials. Expert Opinion on Pharmacotherapy, 2024, 25(5): 611-619. https://doi.org/10.1080/14656566.2024.2343092