Whether through dieting, bariatric surgery, or glucagon-like peptide-1 (GLP-1) receptor agonist therapy, rapid weight loss almost always involves the loss of some lean tissue alongside fat. Unfortunately, there can be serious consequences to losing lean tissue, particularly lean muscle tissue. The results of a new Phase II trial, however, could provide a way for patients with obesity to reap the weight-loss benefits of GLP-1s while minimizing muscle loss. Read on for a summary of the randomized controlled Phase II trial results, which were published in Nature Medicine on March 12, 2026.
Mitigating Muscle Loss as a Side Effect of GLP-1 Use
Losing lean mass is a known consequence of the weight loss associated with GLP-1 use. A peer-reviewed 2024 article in Diabetes, Obesity and Metabolism suggests that, in the case of semaglutide (Ozempic®, Wegovy®), roughly 15 to 40 percent of total weight loss comes from lean body mass rather than fat. Per the article, in some extreme cases, that number can reach 60 percent.
The consequences of GLP-1-induced muscle loss can be far-reaching. First, muscle is metabolically active; thus, losing significant muscle can lower an individual’s resting metabolic rate. Unintended muscle loss can also impair physical strength and balance, particularly in older adults. Seniors who lose muscle are generally more vulnerable to falls.
Enter: bimagrumab, an investigational activin pathway inhibitor and the subject of the Phase II trial published on March 12. The Phase II trial results show that, when combined with semaglutide, bimagrumab resulted in substantial weight loss in patients with obesity compared with either drug alone. Perhaps most importantly, the combination largely preserved lean mass, creating another positive health outcome outside of weight loss alone.
Combining Bimagrumab and Semaglutide
Bimagrumab is described in the study as an “investigational antibody targeting type II activin receptors.” It is specifically designed to block the binding of myostatin and activin A; this mechanism inhibits signaling pathways that regulate muscle growth and adipose tissue metabolism.
Semaglutide, conversely, targets the body’s central mechanisms regulating energy balance. Bimagrumab and semaglutide have profoundly different mechanisms; yet, when used in tandem, these agents resulted in enhanced fat loss without proportional muscle loss in the Phase II study, called the BELIEVE trial.
BELIEVE Phase II Trial Achieves Promising Results
The BELIEVE trial enrolled 507 adults. Each enrolled individual had obesity, as determined by body mass index, and at least one obesity-related health complication. The participants were randomly assigned to nine treatment groups, including placebo, bimagrumab monotherapy, semaglutide monotherapy, and various combinations of the drugs.
At week 72, the participants were evaluated. Those receiving the high-dose combination of both drugs achieved an average 22.1 percent reduction in body weight, compared with 15.7 percent for semaglutide alone and 10.8 percent for bimagrumab alone. Notably, the researchers found that 92 percent of weight loss in the high-dose combination group was from fat mass. This is significantly better than the group that received only semaglutide; those participants saw about 76 percent weight loss from fat mass.
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As mentioned above, not all weight loss is inherently positive, particularly where lean mass is concerned. The bimagrumab and semaglutide combination could represent an important shift in weight-loss drug development: moving beyond weight loss alone toward therapies that improve the quality and composition of weight loss. In other words, future obesity treatments may be designed not simply to help patients lose weight but also to preserve muscle, improve metabolic health, and address unintended consequences of significant weight reduction, including muscle loss.
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