Do weight-loss medicines cause muscle loss?

What does “lean mass” mean?

A DXA scan estimates body compartments, including fat and lean tissue. Lean tissue includes muscle but also water and other non-fat tissue. A fall in measured lean mass is worth studying, but it is not a direct measurement of muscle fibres, strength or physical performance. Losing weight by other means can also involve changes in lean tissue; a scan alone cannot determine whether a medicine uniquely caused a particular pattern.2

What did the semaglutide scan study show?

An exploratory analysis of STEP 1 included 140 adults with overweight or obesity without diabetes who had body-composition scans. Over 68 weeks, measured total lean mass decreased in the semaglutide group, while lean mass as a proportion of total body weight increased because fat also fell. The analysis concerns a subgroup of a larger trial and was reported as a conference abstract; it does not establish how much muscle strength changed or predict an individual’s result. Novo Nordisk funded the parent trial.1

What did the tirzepatide substudy show?

In a SURMOUNT-1 substudy, 160 adults had scans at the start and end of the 72-week trial: 124 in the pooled tirzepatide groups and 36 on placebo. Average lean mass changed by −10.9% from its starting level with tirzepatide and −2.6% with placebo; both fat and lean mass declined. These percentages describe the change in each group’s lean mass, not the percentage of total weight lost that was muscle. The analysis studied a selected subgroup without type 2 diabetes and does not by itself establish strength or long-term health outcomes. Eli Lilly, the manufacturer, funded the study.2

Does less lean mass mean less strength?

Not necessarily. The amount and quality of muscle, strength, physical function, body size and health are related but distinct. A smaller lean-mass measurement alone cannot diagnose muscle disease or tell whether everyday function improved or worsened. Comparisons across studies with different people, treatments, scan methods and follow-up cannot establish that one medicine preserves muscle better than another.12

What happens to strength and fitness?

A 2026 analysis examined a randomized trial of 193 adults with obesity and without diabetes who had first completed a low-calorie diet. For the next year they were assigned liraglutide, supervised exercise, both, or placebo with usual activity. Compared with liraglutide alone, the combined group completed a stair test faster and had higher cardiorespiratory fitness; exercise alone showed similar benefits. Absolute knee strength was generally maintained, while strength expressed relative to body weight changed partly because body weight changed. This study tested a particular exercise programme and liraglutide, not semaglutide or tirzepatide; participants were selected after a diet, and the fitness analysis was secondary.

A separate 2026 review pooled handgrip changes in people taking semaglutide and found the evidence too uncertain to determine its effect on strength. Its main analysis looked at changes within treated groups without a control comparison; no statistically clear average change does not prove strength was preserved or that the medicine caused no change. Different muscles and everyday tasks may behave differently. The review included short and nonrandomized studies, and individual results varied widely. Discuss changes in strength or function with a clinician; suitable activity and nutrition depend on the person.45

What can a reader discuss with a clinician?

If you are concerned about strength, reduced food intake, persistent vomiting or a change in function, discuss the whole picture with a clinician or dietitian. Persistent vomiting needs prompt clinical advice. Individual needs and suitable activity vary, especially with older age or other illnesses. Protein drinks and resistance exercise are often discussed in this context, but a supplement label or a single trial does not establish a personalised plan. See protein powders and muscle evidence, semaglutide and tirzepatide.

For practical questions about appetite, meals and nausea with these medicines, see eating and drinking with semaglutide or tirzepatide.3