trevogrumab + garetosmab + semaglutide

This is a **combination therapy** under clinical investigation for obesity that consists of **trevogrumab** (an anti-GDF8/anti-myostatin monoclonal antibody), **garetosmab** (an anti-activin A monoclonal antibody), and **semaglutide** (a glucagon-like peptide 1 receptor agonist)[1][3][5][7]. The triplet is designed to maximize fat loss and preserve muscle mass during weight reduction: - **Semaglutide** promotes weight loss primarily via appetite suppression and slower gastric emptying, acting as a GLP-1 receptor agonist[2][6][8]. - **Trevogrumab** blocks GDF8 (myostatin), which inhibits muscle growth; antagonism leads to preservation or increase of lean (muscle) mass[1][3][5]. - **Garetosmab** blocks activin A, which is implicated in muscle wasting and metabolic regulation; antagonism aids further muscle mass preservation[1][3][5]. In the phase 2 COURAGE trial (NCT06299098), the three-drug combination ("triplet therapy") resulted in significantly **greater fat mass reduction** while preserving **over 80% of lean body mass** compared to semaglutide alone in patients with obesity[1][5][7]. This combination is experimental and not yet marketed; it is being developed to address the muscle loss often encountered with major weight loss agents.