BELIEVE: Bimagrumab/Semaglutide Combo Yields Substantial Fat Mass Weight Loss, Preserves Lean Mass

The combination of bimagrumab and semaglutide led to a nearly additive fat mass reduction while preserving lean mass with a tolerable safety profile in adults with overweight or obesity.1

These findings were presented as part of a symposium of the phase 2b BELIEVE study results at the 2025 American Diabetes Association (ADA) Scientific Sessions, held June 20-23, in Chicago, Illinois, by lead investigator Steven Heymsfield, MD, Professor at Pennington Biomedical Research Center.

"This study represents another major step forward in the evolution of obesity treatment, building on the significant weight loss benefits of semaglutide and combining it with bimagrumab to improve patient outcomes,” Heymsfield said in a statement.2 “These insights indicate that is not only possible to achieve substantial fat loss, but also to preserve, or even enhance, lean mass in the process.”

Bimagrumab is a first-in-class monoclonal antibody that targets activin type II receptors, promoting muscle preservation and growth, evaluated alone and in combination with semaglutide in the randomized, double-blind, placebo-controlled, multicenter BELIEVE study.

In the study, 507 participants received semaglutide 1.0 or 2.4 mg as a once-weekly subcutaneous injection and/or intravenous (IV) infusion of bimagrumab 10 or 30 mg at weeks 4, 16, 28, and 40. The study primarily evaluated the change in body weight (BW) from baseline, and secondarily evaluated changes in waist circumference, total body fat mass, visceral adipose tissue, and lean mass.

Heymsfield and colleagues found that combination bimagrumab 30 mg/semaglutide 2.4 mg therapy led to greater reductions across clinical outcomes in weight, body fat, visceral fat, and markers of inflammation compared to either treatment alone. Specifically, participants receiving combination therapy experienced a 22.1% decrease in bodyweight (bimagrumab alone, -10.8%; semaglutide alone, −15.7%) and had 92.8% of their total weight loss be from fat mass (bimagrumab alone, 100%; semaglutide alone, 71.8%).1

Most participants (69.8%) on combination therapy achieved at least a 20% weight reduction, compared to 10.9% and 25.0% with bimagrumab or semaglutide alone, respectively. Similarly, 94.0% of participants on combination therapy had at least a 30% fat mass reduction, compared to 50.0% and 36.4% with bimagrumab or semaglutide alone, respectively.1

Bimagrumab alone did slightly outperform the combination on weight loss from fat mass (100%) and total lean mass (+2.5%) but fell behind on other measures. Overall, fat mass reduction with bimagrumab was similar to with semaglutide alone, with minimal change in caloric intake. Participants receiving bimagrumab 30 mg/semaglutide 2.4 mg also had a statistically significant improvement from baseline on SF-36 Physical Functioning score compared to those receiving semaglutide 2.4 mg alone.1

In terms of safety, findings were consistent with known safety profiles of the 2 drugs and there were no new safety signals. Common adverse events (AEs) included muscle spasms, diarrhea, and acne with bimagrumab, and nausea, diarrhea, constipation, and fatigue with semaglutide. Events were similar scross the 4 combination groups, and 9% of combination-treated participants discontinued due to AEs over 72 weeks. There were no deaths. Bimagrumab-containing groups showed early and transient increases in ALT and lipase while semaglutide-containing groups had a sustained increase in lipase.1

“As we enter a new era of obesity treatments, it’s vital to focus not just on the amount of weight lost, but on preserving muscle mass and gaining the health benefits that result from treating obesity,” Samar Hafida, MD, the new Vice President of Obesity Association a division of the American Diabetes Association, added.2 “We are championing research to ensure people living with obesity can have access effective treatments to reduce adiposity while maintaining muscle mass critical to their well-being, and supporting durable long-term outcomes.”

Heymsfield’s disclosures include Tanita Corporation, Novo Nordisk, Lilly, Regeneron, Abbott, and Medifast.

REFERENCES

1. Heymsfield S. BELIEVE Study Results: BELIEVE Study Efficacy and Safety Results: Weight Reduction and Body Composition. Presented at: ADA 2025; June 20-23; Chicago, Illinois.

2. New GLP-1 Therapies Enhance Quality of Weight Loss by Improving Muscle Preservation. News release. ADA. June 23, 2025. https://diabetes.org/newsroom/press-releases/new-glp-1-therapies-enhance-quality-weight-loss-improving-muscle-0