New Research Reexamines GLP-1 Muscle-Loss Concerns

Concerns about Ozempic, Wegovy, and Zepbound have often rested on studies measuring lean body mass rather than muscle directly. The 2021 STEP 1 semaglutide substudy and 2025 SURMOUNT-1 tirzepatide substudy each found a loss of roughly 10 percent of lean mass. But lean mass also includes organs, water, and connective tissue; Henning Langer, PhD, estimates muscle accounts for only about half of it. Weight loss can also reduce liver size, glycogen stores, and the water held with glycogen, affecting scan results without reflecting equivalent muscle-tissue loss.

A small Cell Reports Medicine study examined muscle dimensions and physical performance more directly. Ten men used semaglutide during a 12-week period. Their thigh muscles became slightly smaller, while hand-grip performance was maintained. They also retained the same capacity to extend the knee while pushing against resistance. Langer said the size change may partly reflect reduced fat, stored carbohydrates, and water inside muscle rather than substantial loss of working tissue.

The findings are limited by the study’s size, short length, and exclusion of women. They also do not establish whether the same pattern applies to older adults or people with heart failure, cancer, or neuromuscular disease. Still, a 2024 analysis of two trials found that women with obesity and a form of heart failure reported better well-being and easier physical activity after one year on semaglutide than on placebo. They also covered more distance during a six-minute walking test. Robert F. Kushner, MD, said closer attention remains important for people older than 65, those with chronic kidney or heart disease, people beginning treatment with low muscle mass, and those losing excessive weight.