A recent clinical trial has found that combining semaglutide, a GLP-1 receptor agonist, with bimagrumab, an antibody that blocks activin signaling pathways, leads to greater weight loss while preserving lean body mass. The study, published in Nature Medicine and led by Dr. Steven Heymsfield of Pennington Biomedical Research Center, reports that this combination addresses the loss of lean mass often seen with GLP-1-based therapies.
Dr. Heymsfield explained the significance of these findings: "Obesity treatment has traditionally focused on the number on a scale. Patients with obesity who are at risk for low muscle mass, affecting both physical and metabolic function, may benefit from treatments that maximize fat mass reduction while preserving skeletal muscle," he said. "Bimagrumab and semaglutide work through distinct biological pathways, and when combined, we observed not only a preservation of lean mass but also an additive reduction in fat mass that exceeded what either therapy achieved alone."
The BELIEVE study divided participants into groups receiving bimagrumab alone, semaglutide alone, or the combination of both drugs. Those treated only with bimagrumab lost an average of 10.8% body weight; all weight loss was due to reduced fat mass and there was a 2.5% increase in lean mass. Participants taking only semaglutide lost 15.7% of their body weight on average, with nearly three-quarters of the loss coming from fat mass. The group receiving both drugs experienced an average weight loss of 22.1%, with over 90% of this loss attributed to fat while maintaining lean mass.
The double-blind, placebo-controlled trial used two dosing levels for each drug—10 or 30 mg/kg for bimagrumab administered every twelve weeks and 1.0 or 2.4 mg for semaglutide given weekly—resulting in nine randomized participant groups.
In addition to weight reduction, participants saw up to an 83% drop in high-sensitivity C-reactive protein (hsCRP), which is linked to cardiovascular risk, as well as increased adiponectin levels—a hormone important for insulin sensitivity and fat metabolism. Among those identified as prediabetic at baseline, some combination therapy groups achieved full reversion to normal blood sugar levels.
The drug regimen was generally well tolerated; side effects were consistent with known profiles for each medication but included mild-to-moderate acne and muscle spasms among those taking bimagrumab. Researchers emphasize the need for further studies on adverse events related to bimagrumab and suggest shifting research focus from overall weight or BMI toward more detailed measures like body composition when assessing obesity treatments.
Eli Lilly and Company funded the study’s design through Versanis Bio—a wholly owned subsidiary—which also managed part of the trial before being acquired by Eli Lilly.
