Bimagrumab plus semaglutide boosts weight loss beyond semaglutide alone in phase 2 obesity trial

Obesity is projected to affect nearly 3.3 billion adults by 2035. Incretin-based drugs like semaglutide produce large weight loss, but about 25–40% of the weight lost can be lean tissue, including skeletal muscle and organs. That matters for physical function and metabolic health, especially in people already at risk of low muscle mass. Therapies that maximize fat loss while preserving muscle are therefore of strong interest.

Bimagrumab is a fully human monoclonal antibody that blocks activin type II receptors (ActRIIA and ActRIIB), preventing myostatin and activin signaling. In muscle this has anabolic effects. In adipose tissue it appears to increase lipolysis and lipid mobilization, reducing fat mass. It does not appear to change food intake, so its mechanism complements appetite-suppressing incretins. An earlier phase 2 study in adults with obesity and type 2 diabetes showed reduced fat mass, visceral fat and liver fat alongside increased lean mass.

BELIEVE was a double-blind, placebo-controlled phase 2 trial run from November 2022 to May 2024. It randomized 507 adults with obesity (BMI ≥30, or ≥27 with at least one obesity-related complication; diabetes excluded) equally across nine groups of about 56 each. The groups received placebo, bimagrumab (10 or 30 mg/kg IV every 12 weeks), semaglutide (1.0 or 2.4 mg weekly), or the four bimagrumab–semaglutide combinations. Randomization was stratified by sex. Treatment lasted 48 weeks, followed by an open-label extension to week 72. Participants averaged 47.5 years and 107.5 kg (BMI 37.3), and 57.4% were female. About 74% completed week 48.

The primary endpoint was absolute weight change at week 48. Least-squares mean changes were −3.3 kg for placebo, −9.3 kg for bimagrumab 30 mg/kg, −14.2 kg for semaglutide 2.4 mg, and −17.8 kg for the high-dose combination, all P<0.001 versus placebo. The combination thus lost about 3.6 kg more than semaglutide 2.4 mg alone. Weight continued to improve through week 72. The authors also report that the combination preserved lean mass while reducing visceral fat. Bimagrumab-associated adverse events included muscle spasms, diarrhea and acne. Semaglutide-associated events were nausea, diarrhea, constipation and fatigue. Discontinuations for adverse events were highest with bimagrumab alone (14.0–21.4%), versus 3.6–8.8% with semaglutide, 5.3–12.5% with combinations and 3.6% with placebo. Overall safety was consistent with the known profiles of both drugs.

These results suggest that targeting activin signaling alongside incretin therapy could improve the quality of weight loss, not just the quantity. Important caveats apply. This is a phase 2 study, groups were small, the sponsor was Eli Lilly, and bimagrumab is investigational. Functional benefits of preserved muscle, such as strength and mobility, and the tolerability of the combination need testing in larger, longer phase 3 trials. This summary draws on the abstract and the available results sections, so detailed body-composition and secondary outcome data are not reproduced here.