Adults with obesity who received a combination of bimagrumab and semaglutide experienced greater weight loss than those treated with either therapy alone in a phase 2 randomized clinical trial.
The double-blind, placebo-controlled trial enrolled 507 adults with obesity or overweight and at least one obesity-related complication but without diabetes. Participants were randomly assigned to nine treatment groups receiving placebo, bimagrumab alone, semaglutide alone, or combinations of the two drugs for 48 weeks, followed by an open-label extension through week 72.
Bimagrumab is a monoclonal antibody that targets activin type II receptors, blocking signaling pathways involved in muscle and fat regulation. The drug has been investigated as a strategy to reduce fat mass while preserving or increasing lean muscle during weight loss.
The greatest reductions in body weight were observed among participants receiving the highest-dose combination of bimagrumab and semaglutide. At week 48, mean weight reduction reached 17.8 kg – exceeding the losses observed with semaglutide alone (14.2 kg), bimagrumab alone (9.3 kg), or placebo (3.3 kg).
Weight-loss differences persisted during the extension phase. By week 72, participants receiving the high-dose combination had lost an average of 24.2 kg, corresponding to approximately 22% of baseline body weight.
Body composition analyses suggested that the combination therapy produced larger reductions in total fat mass and visceral adipose tissue than either drug alone. Lean mass was largely preserved compared with semaglutide monotherapy, in which reductions in lean tissue accounted for a greater proportion of total weight loss.
Clinical improvements were also observed in metabolic measures. Reductions in glycated hemoglobin were greater in groups receiving semaglutide-containing regimens, and a higher proportion of participants with prediabetes at baseline achieved normoglycemia during follow-up.
Safety findings were consistent with the known profiles of the two drugs. Muscle spasms, acne, and diarrhea were more frequently reported among participants receiving bimagrumab, whereas nausea, constipation, diarrhea, and fatigue were common in semaglutide-treated groups. No deaths were reported during the trial.
The authors noted that the results provide a basis for further trials evaluating combination approaches that target both adipose tissue and muscle pathways in obesity. They emphasize that longer-term studies will be needed to assess durability, safety, and potential cardiometabolic benefits of this strategy.
Source: Nature Medicine
