Combination of semaglutide and muscle-preserving antibodies helps preserve lean mass
Approximately 35% of the weight loss observed with semaglutide treatment was due to a decrease in lean mass, according to interim results from the phase 2 COURAGE trial. The combination of semaglutide and muscle-preserving antibodies in patients with obesity mitigated lean mass loss by 50%–80%, while further promoting loss of fat mass.
The ongoing phase 2 COURAGE trial investigates the effects of novel combinations of the GLP-1RA semaglutide and trevogrumab (anti-GDF8/anti-myostatin) with or without garetosmab (anti-activin A) on the quality of weight loss in persons with obesity. The three primary endpoints were percentage change in lean mass, fat mass, and body weight from baseline to week 26. The interim analysis was performed when 50% of patients reached week 26.
The COURAGE trial is divided into two phases, a 26-week weight-loss phase and a 26-week weight-maintenance phase. In the weight-loss phase, patients were randomized to receive semaglutide monotherapy or semaglutide in combination with two different doses of trevogrumab (lower- or higher-dose combination) or higher-dose trevogrumab plus garetosmab (triplet). In the weight-maintenance phase, patients will receive either higher-dose trevogrumab monotherapy or placebo.
In the interim analysis, triplet therapy led to an 80.9% preservation of lean mass (n=147) compared with semaglutide monotherapy (n=151). In the combination groups with a lower dose (n=149) and higher dose (n=152), 50.8% and 51.3% more lean mass was preserved, respectively, compared to semaglutide monotherapy. Greater reductions in fat mass were observed when combining semaglutide with trevogrumab with or without garetosmab compared with semaglutide monotherapy (17.8% in the lower-dose combination group, 15.1% in the higher-dose combination group, and 27.3% in the triplet group).
In COURAGE, the combination of semaglutide with trevogrumab was generally well-tolerated. There were higher rates of discontinuations due to tolerability issues and other adverse events in the triplet group.