BELIEVE Trial: Semaglutide + Bimagrumab—Fat Loss with Lean-Mass Preservation

The BELIEVE phase 2 randomized trial evaluated semaglutide in combination with bimagrumab in adults with obesity, and it notes an emphasis on measures such as body composition alongside weight and BMI. The study’s design included blinded bimagrumab or placebo assignment, while semaglutide was administered open-label.

In the report, the combination regimen is described as producing greater fat loss while largely preserving lean mass compared with either agent alone. As reported for the highest-dose groups at week 72, participants receiving bimagrumab 30 mg/kg plus semaglutide 2.4 mg lost an average of 22.1% of body weight, compared with 15.7% with semaglutide 2.4 mg alone and 10.8% with bimagrumab 30 mg/kg alone. At week 72, 92.2% of the weight loss in the high-dose combination group was attributable to fat mass, versus 75.6% in the semaglutide 2.4 mg group, while weight loss in the bimagrumab 30 mg/kg group was fully attributable to fat mass. Lean mass was described as largely preserved in the combination groups, while bimagrumab 30 mg/kg alone was reported to produce a 2.5% increase in lean mass at week 72.

Trial structure in the same account centers on randomized comparisons of placebo, bimagrumab alone, semaglutide alone, and combination therapy. The trial included nine randomized groups spanning bimagrumab dosing at 10 or 30 mg/kg administered intravenously, with loading doses at randomization and week 4 followed by dosing every 12 weeks, semaglutide dosing at 1.0 or 2.4 mg administered subcutaneously once weekly, and four combination groups receiving dose levels of both agents. The framework enabled monotherapy-versus-combination comparisons while varying dose levels within each drug.

Beyond body composition, the report describes additional metabolic and inflammatory signals observed during the trial. It reports least-squares mean hsCRP reductions at week 48 ranging from 71.5% to 83.1% in the combination groups, along with increases in adiponectin. Among participants with baseline indicators of prediabetes, the report states that by week 48, 100% reversion to normoglycemia was achieved only in the combination groups except the low-dose combination, and by week 72, normoglycemia was achieved in all participants with baseline prediabetes in the combination groups.

Safety is described as consistent with the known profiles of the individual drugs. The report notes muscle spasms, diarrhea, and acne with bimagrumab, and nausea, diarrhea, constipation, and fatigue with semaglutide, with similar events in the combination groups. It also states that additional research is needed to better understand specific adverse events such as muscle spasms and acne.

Key Takeaways:

• The combination group was reported to have greater overall weight loss, with a higher share of loss from fat mass and relative lean-mass preservation compared with either monotherapy, particularly in the highest-dose groups at week 72.
• The trial was described as using nine randomized groups that included placebo, two dose levels each of bimagrumab and semaglutide, and four combination groups, with the primary endpoint defined as absolute change in body weight at week 48 and longer-term extension results reported through week 72.
• Reported accompanying details included hsCRP and adiponectin changes, full reversion to normoglycemia in combination groups among participants with baseline prediabetes at later assessments, and safety findings described as consistent with the known profiles of bimagrumab and semaglutide.