Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial
Steven B. Heymsfield, Louis J. Aronne, Penelope S. Montgomery, Lloyd B. Klickstein, Laura A. Coleman, Kiran Dole, Linda Mindeholm, Susan E. Spruill, Xingyuan Li, Kenneth M. Attie, for the BELIEVE trial investigators
Abstract
Abstract Bimagrumab is an investigational antibody targeting type II activin receptors, intended to reduce total body and visceral fat mass and promote muscle growth. In this double-blind, placebo-controlled phase 2, trial, 507 adults with obesity (body mass index ≥30 kg m − 2 or ≥27 kg m − 2 with at least one obesity-associated complication (excluding diabetes) were randomized to nine groups (1:1:1:1:1:1:1:1:1 ratio) to receive treatment for 48 weeks: placebo, bimagrumab (10 mg kg −1 or 30 mg kg −1 intravenously every 12 weeks), semaglutide (1.0 mg or 2.4 mg subcutaneously once a week) and combinations thereof. An open-label treatment extension to week 72 followed. Randomization was stratified by sex across the treatment groups. The primary and secondary endpoints were absolute change from baseline in body weight at week 48 and week 72, respectively. The least squares mean absolute changes in body weight at week 48 were −9.3 kg (bimagrumab 30 mg kg −1 ), −14.2 kg (semaglutide 2.4 mg) and −17.8 kg (bimagrumab 30 mg kg −1 plus semaglutide 2.4 mg—that is, high-dose combination) versus −3.3 kg (placebo) (all P < 0.001 versus placebo). Continued improvements were observed through week 72. Common adverse events for bimagrumab included muscle spasms, diarrhea and acne, and semaglutide was associated with nausea, diarrhea, constipation and fatigue. Bimagrumab plus semaglutide resulted in substantial reductions in body weight, and safety was consistent with the known safety profiles of both drugs. ClinicalTrials.gov identifier: NCT05616013 .