Introduction Most obesity therapies reduce body fat, but they also cause a meaningful loss of lean mass, including skeletal muscle. This matters because preserving muscle is important for physical function, metabolic health, and long-term weight loss.
Introduction
Most obesity therapies reduce body fat, but they also cause a meaningful loss of lean mass, including skeletal muscle. This matters because preserving muscle is important for physical function, metabolic health, and long-term weight loss. Bimagrumab is an investigational monoclonal antibody that blocks activin type II receptors, promoting fat loss and muscle preservation/growth. Semaglutide, a GLP-1 receptor agonist, mainly reduces weight by lowering appetite and food intake. The BELIEVE phase 2 trial tested whether combining these two drugs could produce greater weight loss with better body composition than either alone.
Summary
In this randomised phase 2 trial, 507 adults with obesity received placebo, bimagrumab, semaglutide, or combinations for 48 weeks, followed by extension to 72 weeks. At week 48, body weight fell by 9.3 kg with high-dose bimagrumab alone, 14.2 kg with semaglutide 2.4 mg, and 17.8 kg with the high-dose combination, versus 3.3 kg with placebo. By week 72, the high-dose combination achieved about 22.1% weight loss, greater than semaglutide alone.
The major strength of the combination was body composition. It produced striking reductions in total fat mass and visceral fat while preserving lean mass far better than semaglutide alone. At week 72, the high-dose combination reduced fat mass by 45.7% and visceral adipose tissue by 58.2%, while limiting lean-mass loss. Glycemic measures, waist circumference, hsCRP, and several metabolic markers also improved.
Adverse effects reflected known profiles of both drugs. Bimagrumab was associated with muscle spasms, diarrhea, and acne, while semaglutide caused nausea, diarrhea, constipation, and fatigue.
Key Message
This study suggests that bimagrumab plus semaglutide may offer a next-generation obesity treatment approach: substantial weight loss with enhanced fat loss and relative preservation of muscle mass.
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