Will weight-loss drugs cause me to lose muscle?

When you lose weight, some of it will be fat loss, and some proportion (usually around 25%) will be lean mass and/or muscle mass. It should be noted that lean mass loss is not always muscle mass loss per se, as lean mass comprises muscle, but also bone, connective tissue, organs, and body water content. The goal of most fat loss programs is to improve body composition — in other words, to increase the body’s proportion of lean mass to fat mass.

Most clinical trials of weight loss drugs such as semaglutide and other GLP-1 agonists (e.g., tirzepatide) report weight loss as a secondary if not a primary outcome, and the results don’t seem to indicate a disproportionate loss of muscle mass. For example, in a 72-week study comparing once-weekly tirzepatide (5, 10, and 15 mg) to placebo, fat loss was 34% on average, and the ratio of total fat mass to lean mass decreased from 0.93 to 0.7 (indicating a favorable improvement in body composition).^[1] In adults with type 2 diabetes, semaglutide also reduced body fat mass by 10% and the proportion of fat mass by 1.4 percentage points. Although lean mass was also reduced by 4%, the proportion of lean mass increased by 1.2 percentage points, and the ratio of fat mass to lean mass decreased.^[2] Semaglutide also reduced visceral fat while preserving fat-free mass and skeletal muscle mass in adults with type 2 diabetes,^[3] and in a 24-week retrospective study of adults taking once-weekly semaglutide, body fat decreased while whole-body lean mass and appendicular skeletal muscle mass (ASMI, the total mass of arm and leg muscles) were preserved.^[4]

Thus, recent clinical data don’t seem alarming regarding the impact of weight-loss drugs on lean mass. However, being prudent about diet and exercise can quell any worries that may exist: sufficient protein intake and regular resistance exercise, when paired with weight loss, can help increase/maintain muscle mass and may even help promote fat loss.^[5][6]