Trevogrumab cuts semaglutide-associated lean mass loss by about half

Clinical takeaway: When discussing semaglutide for obesity, address muscle health alongside weight loss. Trevogrumab reduced lean mass loss in this trial, but it remains investigational, and the study did not establish whether the difference improves strength or daily function.

Weight loss with semaglutide can include a substantial loss of lean mass, raising questions about how best to protect muscle during treatment. In the phase 2 COURAGE trial, adding the myostatin-blocking antibody trevogrumab reduced lean mass loss in adults with obesity.

The trial enrolled 975 participants in two parts. After 26 weeks, lean mass had fallen 6.6% with semaglutide plus placebo, compared with 3.4% and 3.9% with two trevogrumab doses. In a separate year-long comparison, the 75 mg dose significantly reduced lean mass loss relative to semaglutide plus placebo. The 25 mg dose did not.

An exploratory MRI substudy found that trevogrumab reduced thigh muscle-volume loss by about 70% relative to semaglutide plus placebo. A prespecified subgroup analysis also suggested that participants with low lean mass at baseline experienced greater lean-mass loss with semaglutide alone and numerically greater preservation with trevogrumab.

The study also examined what happened after semaglutide was stopped. Among participants assigned trevogrumab for the following 26 weeks, lean mass was 0.4% above its starting level versus 2.4% below baseline among those assigned placebo. Both groups remained below baseline for body weight and fat mass.

Trevogrumab alone was generally well tolerated. Adding a second antibody, garetosmab, preserved more lean mass but brought substantially more serious adverse events and treatment discontinuations, including frequent muscle spasms.

“These findings suggest that obesity treatment may be further optimised by considering not only the magnitude of weight loss but also lean mass and skeletal muscle preservation,” the authors wrote. They noted that whether greater muscle preservation translates into improvements in physical function or clinical outcomes remains unknown.

Regeneron said it plans to evaluate trevogrumab in older adults with obesity and decreased muscle mass or strength.

Sources: European Association for the Study of Diabetes. (2026 Sep 30). Trevogrumab (anti-myostatin) can help preserve lean mass during and after semaglutide-induced weight loss; Regeneron Pharmaceuticals. (2026 Oct 1). Phase 2 COURAGE Trial Confirms Trevogrumab Prevents Lean Mass and Muscle Loss During GLP-1 Receptor Agonist-induced Weight Loss