Trevogrumab (anti-GDF8) with or without garetosmab (anti-activin A) for prevention of muscle loss during semaglutide-induced weight reduction in people with obesity (COURAGE): a two-part, phase 2, double-blind, placebo-controlled, randomised trial.

In the US COURAGE phase 2 trial, semaglutide caused lean-mass loss, while trevogrumab preserved lean mass at week 26 with an estimated treatment difference up to +4·5%.

• Why it matters: Rapid GLP-1 receptor agonist weight loss is linked to pronounced muscle loss, and blocking muscle-mass negative regulators (GDF8 and activin A) could improve body composition during weight reduction.
• What they did: Across 60 US sites, adults with obesity (BMI ≥30 kg/m²) received semaglutide for 26 weeks (part A) or 52 weeks (part B) with placebo or trevogrumab (200/400 mg in part A; 25/75 mg in part B), with optional garetosmab 10 mg/kg in part A.
• The result: Lean mass fell with semaglutide plus placebo (−6·6% at week 26; −7·3% at week 52), but trevogrumab increased lean mass versus placebo (ETD +3·1% to +4·5% at week 26; +1·5% to +3·1% at week 52); garetosmab addition improved bodyweight and body composition but had worse safety, including higher serious adverse events and discontinuations.

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