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March 4, 2026Nature Medicine49 citationsOpen Access

Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial

SHSteven B. HeymsfieldLALouis J. AronnePMPenelope S. Montgomery

Key Points

  • This trial aims to evaluate the effectiveness of bimagrumab and semaglutide for reducing body weight in patients with obesity.
  • Randomized, double-blind, placebo-controlled design
  • Involved 507 adults with obesity
  • Treatment groups included various doses of bimagrumab and semaglutide, both alone and in combination
  • Primary endpoint was change in body weight at week 48 and secondary at week 72
  • Weight reduction of −17.8 kg with high-dose bimagrumab plus semaglutide
  • Weight reduction of −14.2 kg with semaglutide alone
  • Compared to placebo which saw a reduction of −3.3 kg
  • Continued improvements in weight loss were noted through week 72
  • Common adverse events were mild and consistent with drug profiles

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 . Bimagrumab is a monoclonal antibody targeting type II activin receptors. In a randomized trial, bimagrumab combined with semaglutide led to up to 17.8 kg weight reduction, surpassing the effects of semaglutide alone (up to 14.2 kg). Notably, the combination preserved lean mass while reducing visceral fat, highlighting its potential for effective obesity management.

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Cite This Study

Heymsfield et al. (2026) studied this question.

synapsesocial.com/papers/69a7ccb2d48f933b5eed8752https://doi.org/10.1038/s41591-026-04204-0
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