The Wegovy, Zepbound and Foundayo labels each state that the medicine lowers body weight with greater fat mass loss than lean mass loss. The two published DXA body composition analyses from the pivotal trials agree on direction but also show that lean mass goes down. In the SURMOUNT-1 tirzepatide substudy, the abstract reports lean mass change of -10.9% versus -2.6% with placebo, and that about 75% of the weight lost was fat and 25% lean mass, for both tirzepatide and placebo. In the STEP 1 semaglutide analysis, the abstract reports lean body mass down 9.7% while its proportion of total body mass rose. Both are small substudies, and “lean mass” is not the same thing as skeletal muscle.
The question people are really asking
Search for GLP-1 side effects and you will find a lot of confident claims about muscle: that these drugs destroy it, or that the worry is overblown. The primary sources are more careful than either camp: a label statement, two body composition analyses from large trials, and a review on why the measurement is easy to over-read. We found no source that quantifies muscle strength or function outcomes in the label text we reviewed, so this article does not make claims about them.
What the labels say
We checked the Wegovy label (revised 06/2026), the Zepbound label (08/2026) and the Foundayo label (07/2026) on 13 October 2026. The statement sits in section 12.2 (Pharmacodynamics) of each:
| Label | What section 12.2 says about body composition |
|---|---|
| Wegovy | Semaglutide lowers body weight with greater fat mass loss than lean mass loss. |
| Zepbound | Tirzepatide lowers body weight with greater fat mass loss than lean mass loss. |
| Foundayo | Reduces body weight, with greater fat mass loss than lean mass loss. |
Two features of this wording matter. It is a single sentence in a pharmacology section, not a warning, and it gives no numbers. And “greater fat mass loss than lean mass loss” is a statement about the balance, not a claim that lean mass is spared: it is consistent with lean mass falling by a smaller amount. The Mounjaro and Ozempic labels (the type 2 diabetes products) did not contain an equivalent sentence in the text we searched.
Why “lean mass” is not “muscle”
The studies below use dual-energy X-ray absorptiometry (DXA), which splits the body into fat mass and lean (fat-free) mass. A 2024 review in the Journal of the Endocrine Society by Tinsley and Heymsfield, “Fundamental Body Composition Principles Provide Context for Fat-Free and Skeletal Muscle Loss With GLP-1 RA Treatments”, makes the point that fat-free mass and skeletal muscle are often conflated even though they are different levels of the body composition model: fat-free mass is a molecular component, skeletal muscle is a tissue. The review also discusses the potential for an obligatory loss of fat-free mass when adipose tissue shrinks, and describes resistance exercise training and increased protein intake as selected countermeasures. We cite it for the measurement distinction only; exercise and protein plans are a conversation for you and your clinician.
SURMOUNT-1 (tirzepatide) DXA substudy
The analysis is Look M, Dunn JP, Kushner RF, et al., “Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight,” Diabetes Obesity and Metabolism, 2025 (PMID 39996356). From the PubMed abstract:
- Participants: 160 of the 2,539 people in SURMOUNT-1 had DXA at baseline and Week 72 (pooled tirzepatide doses n = 124, placebo n = 36); 73% female, mean weight 102.5 kg, BMI 38.0 kg/m2.
- Change from baseline to Week 72 in body weight, fat mass and lean mass: -21.3%, -33.9% and -10.9% with tirzepatide, versus -5.3%, -8.2% and -2.6% with placebo (p < 0.001 for all comparisons).
- Of the body weight lost, “approximately 75% was fat mass and 25% was lean mass for both tirzepatide and placebo,” and the proportions stayed consistent across most subgroups (sex, age, and weight-loss tertiles).
Read carefully, this says two things at once. Lean mass fell more with tirzepatide than with placebo in absolute percentage terms, which is what you would expect when people lose far more weight. But the share of weight lost that was lean mass was about the same as in the placebo group. The authors’ own conclusion is that the proportion of body weight lost as fat or lean mass was relatively consistent. Note the sourcing: the authors include Eli Lilly employees and shareholders, and Lilly funded the study, per the PubMed record. The PubMed record also lists a published correction to this paper (Diabetes Obes Metab 2025, PMID 40832789). We could not read the text of the correction, so we do not know whether it affects the figures above; check the journal’s current version before quoting them.
STEP 1 (semaglutide) DXA analysis
The semaglutide data we found is an exploratory analysis of STEP 1 by Wilding J, Batterham R, Calanna S, and colleagues, “Impact of Semaglutide on Body Composition in Adults With Overweight or Obesity: Exploratory Analysis of the STEP 1 Study,” published in the Journal of the Endocrine Society in 2021. It is an abstract, not a full paper, which limits how much detail we can verify. The abstract reports:
- Participants: 140 (semaglutide n = 95, placebo n = 45), mean weight 98.4 kg, BMI 34.8 kg/m2, 76% female, from 9 sites; body composition measured by DXA at screening and week 68.
- Body weight change from baseline to week 68: -15.0% with semaglutide versus -3.6% with placebo.
- Total fat mass -19.3% and regional visceral fat mass -27.4% with semaglutide. Total lean body mass decreased -9.7%, although its proportion of total body mass increased by 3.0 percentage points.
- No major body composition changes with placebo.
The abstract itself says semaglutide 2.4 mg was associated with reduced total fat mass and regional visceral fat mass and an increased proportion of lean body mass. That last phrase is about proportion of body mass, and it is accurate precisely because fat fell by more than lean tissue did. It should not be read as lean mass being preserved in absolute terms: the same abstract reports lean mass falling 9.7%.
How to read the two studies together
| SURMOUNT-1 DXA substudy (tirzepatide) | STEP 1 DXA analysis (semaglutide 2.4 mg) | |
|---|---|---|
| Participants with DXA | 160 (124 tirzepatide, 36 placebo) | 140 (95 semaglutide, 45 placebo) |
| Time point | Week 72 | Week 68 |
| Body weight change | -21.3% (placebo -5.3%) | -15.0% (placebo -3.6%) |
| Fat mass change | -33.9% (placebo -8.2%) | -19.3% |
| Lean mass change | -10.9% (placebo -2.6%) | -9.7% |
| Format | Full paper, with a published correction | Conference abstract |
It would be tempting to compare the two columns and decide which drug is better for muscle. The sources do not allow that. They enrolled different populations, measured at different times, and the semaglutide abstract does not report the placebo lean mass figure, and the two were never compared in a head-to-head body composition analysis in what we reviewed. What can be said is narrower: in both programs, DXA lean mass fell during large weight loss, fat mass fell by more, and the labels describe the same pattern.
Limits to keep in mind
- Small substudies. Fewer than 7% of SURMOUNT-1 participants (160 of 2,539) contributed DXA data; STEP 1’s analysis included 140 people from 9 sites.
- Funded by the manufacturers. The SURMOUNT-1 paper has Lilly authors and funding, per its record. Readers should weigh that.
- DXA measures lean mass, not strength or function. Nothing in these abstracts tells you whether physical function changed.
- Not every GLP-1 product is covered. We found no equivalent DXA analysis for Foundayo (orforglipron) in the sources we checked, beyond its label sentence.
What to ask your prescriber
If you are older, already have low muscle mass, have a health condition that affects mobility, or simply want to understand your own plan, ask what monitoring makes sense, whether resistance training and protein intake should be part of your plan (the Tinsley and Heymsfield review discusses both as countermeasures), and how quickly your weight is expected to fall. These are questions, not findings from the label.
Frequently asked questions
Do GLP-1 medicines cause muscle loss?
The labels say fat mass loss is greater than lean mass loss, and the DXA substudies reported lean mass declines alongside much larger fat mass declines. Lean mass is not identical to muscle, and the sources we reviewed do not measure muscle function.
How much of the weight lost is muscle?
In the SURMOUNT-1 substudy abstract, approximately 25% of weight lost was lean mass, for both tirzepatide and placebo. The STEP 1 abstract reports lean mass down 9.7% but no lean share of weight lost in the text we saw.
Is DXA lean mass the same as muscle?
No. A review by Tinsley and Heymsfield notes that fat-free mass and skeletal muscle are often conflated but sit at different levels of the body composition model.
Does the Foundayo label say anything about this?
Yes: it says Foundayo reduces body weight, with greater fat mass loss than lean mass loss. We found no DXA study for it in the sources we reviewed.
Sources
- Look M, Dunn JP, Kushner RF, et al. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. Diabetes Obes Metab 2025;27(5):2720-2729. PubMed record fetched 13 October 2026.
- Correction to the SURMOUNT-1 body composition paper, Diabetes Obes Metab 2025;27(11):6823. Text not reviewed.
- Wilding J, Batterham R, Calanna S, et al. Impact of Semaglutide on Body Composition in Adults With Overweight or Obesity: Exploratory Analysis of the STEP 1 Study. J Endocr Soc 2021 (abstract), via Europe PMC, fetched 13 October 2026.
- Tinsley GM, Heymsfield SB. Fundamental Body Composition Principles Provide Context for Fat-Free and Skeletal Muscle Loss With GLP-1 RA Treatments. J Endocr Soc 2024;8(11):bvae164 (abstract reviewed).
- Novo Nordisk, Wegovy prescribing information, revised 06/2026, section 12.2, fetched 13 October 2026.
- Eli Lilly and Company, Zepbound prescribing information, revised 08/2026, section 12.2, fetched 13 October 2026.
- Eli Lilly and Company, Foundayo prescribing information, revised 07/2026, section 12.2, fetched 13 October 2026.
Medical disclaimer. This article is informational, was prepared by the GLP-1.Reviews editorial team from the public sources listed above, and has not been reviewed by a physician. It is not medical advice. Label wording can change; confirm the instructions for your product with the Medication Guide that came with it. Talk to your prescriber or pharmacist about your own treatment, and see our medical disclaimer and editorial standards.
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