Short answer
Some lean mass is lost, as with any major weight loss, but most of what goes is fat. In a SURMOUNT-1 scan substudy, about 75% of weight lost on tirzepatide was fat and 25% lean mass. In STEP 1, semaglutide cut lean mass by 9.7% but fat by 19.3%, so the share of lean mass in the body rose.
What the scan studies found
Both big trials ran DXA body scans on a subset of patients. In the SURMOUNT-1 substudy of 160 adults, published in 2025, people on tirzepatide lost 21.3% of body weight over 72 weeks, including 33.9% of fat mass and 10.9% of lean mass. About three quarters of the weight lost was fat and one quarter lean mass, the same split seen with placebo. In the STEP 1 substudy of 140 adults, semaglutide 2.4 mg cut total fat mass by 19.3% and lean mass by 9.7% over 68 weeks. The FDA labels for Zepbound and Wegovy both state that the drug lowers weight with greater fat loss than lean loss.
Lean mass is not the same as muscle
DXA lean mass counts everything that is not fat or bone, including muscle, organs and water. So a drop in lean mass is not a direct measure of muscle lost, and the scan results covered here do not measure strength. Because fat fell faster than lean mass, the proportion of lean mass in the body went up in STEP 1, by 3.0 percentage points. Whether the lean mass lost matters for strength and function, especially in older adults, is still being studied.
Protecting muscle while you lose weight
Both drugs are approved for use with a reduced-calorie diet and more physical activity, per the FDA labels. Research outside these trials offers a guide. A 2018 meta-analysis of 49 trials found that resistance training plus adequate protein builds strength and fat-free mass, with little extra gain above about 1.6 g of protein per kg a day. Those studies were not done in people on GLP-1 drugs, so treat them as sensible general guidance. Talk with your prescriber about a strength plan and a protein target that suit your health.
Related questions
Is the lean mass lost on tirzepatide higher than on placebo?
In absolute terms yes, because far more weight was lost. As a share of total weight lost, it was about the same, roughly 25%, in both groups.
Are older adults at more risk?
In SURMOUNT-1, post hoc subgroups, including age groups, showed a similar fat-to-lean split in most cases. Older adults with low muscle to begin with should still discuss this with their doctor.
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Published 2026-09-30 · Last checked 2026-09-30
Educational content, not medical advice. Made for the United States.