Evidence Grade C — Moderate human evidence. 74 published studies, 52 human. 17 registered clinical trials.
Medically reviewed by a licensed medical professional
Bimagrumab is a monoclonal antibody — not a peptide — that simultaneously reduces body fat while increasing lean muscle mass. Acquired by Eli Lilly for $1.9 billion, it is being developed as a partner to GLP-1 drugs like tirzepatide. Its unique value is addressing the muscle loss that typically accompanies weight loss with current obesity medications — ensuring patients lose fat, not muscle.
Bimagrumab is also known by these brand and alternate names:
74 published studies: 52 human, 5 animal, 2 in-vitro, 31 reviews
Bimagrumab is in Phase II/III development (not yet approved). A Phase II trial (75 patients with type 2 diabetes and obesity) showed 20.5% fat mass reduction with 3.6% lean mass increase — essentially reshaping body composition without net appetite suppression. The BELIEVE Phase IIb trial (507 patients) showed that bimagrumab plus semaglutide achieved 22% weight loss with the weight lost being 88% fat — significantly better body composition than semaglutide alone.
Bimagrumab is not a peptide. Its strategic significance is as a combination partner to address the muscle loss problem inherent in weight loss with current obesity drugs. Eli Lilly's acquisition positions it alongside tirzepatide.
Bimagrumab blocks the activin type II receptors that normally transmit muscle-limiting signals from myostatin, activin, and GDF-11. By removing these growth-restraining signals, the antibody promotes muscle protein synthesis and fat mobilisation simultaneously. Crucially, bimagrumab does not suppress appetite — it works through a fundamentally different mechanism from GLP-1 agonists, making it a natural combination partner.
The BELIEVE trial (507 patients) showed that bimagrumab combined with semaglutide achieved 22% total weight loss, with 88% of the weight lost being fat — significantly better body composition than semaglutide alone. In an earlier trial, it produced 20.5% fat mass reduction alongside a 3.6% increase in lean muscle mass. This body composition advantage addresses a genuine limitation of current obesity treatments: rapid weight loss typically includes significant muscle loss, which can reduce metabolic rate and physical function. Phase 2 trials combining bimagrumab with tirzepatide are underway, but Phase 3 has not yet been initiated. Side effects include muscle spasms, acne, and temporary liver enzyme elevations. An earlier trial in inclusion body myositis (a muscle disease) failed its primary endpoint.
PeptideTrace tracks 17 registered clinical trials for Bimagrumab sourced from ClinicalTrials.gov.
Effect of Tirzepatide and Bimagrumab on Body Composition, Insulin Sensitivity, and Bone in Adults With Obesity
A Study of Bimagrumab (LY3985863) and Tirzepatide (LY3298176), Alone or in Combination, in Participants With Obesity or Overweight With Type 2 Diabetes
A Study of Bimagrumab Alone (LY3985863) and Bimagrumab With Tirzepatide (LY900042) in Healthy Participants
A Study to Investigate Weight Management With Bimagrumab (LY3985863) and Tirzepatide (LY3298176), Alone or in Combination, in Adults With Obesity or Overweight
Safety and Efficacy of Bimagrumab and Semaglutide in Adults Who Are Overweight or Obese
Bimagrumab (BYM338) is a fully human IgG1 monoclonal antibody targeting activin type II receptors (ActRIIA and ActRIIB). NOTE: This is a full monoclonal antibody, NOT a peptide. Molecular weight approximately 150 kDa. Originally developed by Novartis/MorphoSys; licensed to Versanis Bio; Eli Lilly acquired Versanis in July 2023 for approximately $1.9 billion. Currently administered as intravenous infusion, with a subcutaneous formulation under development by Lilly.
Bimagrumab blocks signaling of myostatin, activin A, and GDF11 through activin type II receptors, disinhibiting skeletal muscle protein synthesis and hypertrophy while simultaneously promoting fat mobilization and brown adipose tissue differentiation. Critically, the compound does NOT suppress appetite, distinguishing its mechanism from all incretin-based therapies. The result is simultaneous fat mass reduction and lean mass preservation or increase, addressing the fundamental body composition limitation of GLP-1-based weight loss therapies.
Phase 2 T2D/obesity (Heymsfield et al., JAMA Network Open 2021; N=75): fat mass decreased -20.5% versus -0.5% placebo (P<0.001); lean mass increased +3.6% versus -0.8% (P<0.001); HbA1c improved -0.76% versus +0.04% (P=0.005). BELIEVE Phase 2b (N=507; ADA 2025; Nature Medicine 2026): bimagrumab 30 mg/kg plus semaglutide 2.4 mg achieved -22.1% weight loss at 72 weeks versus -15.7% with semaglutide alone. Body composition quality: 92.8% of weight loss was fat in the combination group versus 71.8% with semaglutide alone. Lean mass loss was only 2.6% (combination) versus 7.9% (semaglutide alone), representing 67% more muscle preservation. Bimagrumab monotherapy produced -10.8% weight loss with 100% derived from fat and +2.5% lean mass gain.
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
Danuglipron's original twice-daily formulation achieved 8–13% weight loss in Phase IIb but with treatment discontinuation rates exceeding 50%, with nausea affecting up to 73% of patients. Pfizer discontinued the twice-daily formulation and is developing a once-daily modified-release version. Danuglipron is not a peptide. Its development trajectory illustrates that even effective weight loss compounds can fail commercially if tolerability is inadequate. The reformulation effort aims to reduce peak drug concentrations that likely drive the gastrointestinal side effects.
Setmelanotide is marketed as Imcivree (Rhythm Pharmaceuticals; approved November 2020 for POMC, PCSK1, or LEPR deficiency; June 2022 for Bardet-Biedl syndrome; December 2024 expanded to patients aged 2 years and older). Genetic testing confirming an eligible mutation is required before treatment. In patients with POMC or PCSK1 deficiency, approximately 80% achieved at least 10% weight loss in clinical trials. In Bardet-Biedl syndrome, 32.3% achieved the same threshold. The most common side effects are injection-site reactions and skin darkening (due to the melanocortin pathway's connection to pigmentation). Setmelanotide exemplifies precision medicine — it is highly effective in the specific genetic populations it targets but is not indicated for common obesity.
CT-388 is in Phase II/III development (not yet approved). Phase II results (469 patients, 48 weeks) showed 22.5% placebo-adjusted weight loss at the highest dose, with low discontinuation rates due to adverse events (5.9%). Phase III trials are underway. The combination of high efficacy and low discontinuation rates in Phase II is notable — many obesity drugs achieve high weight loss but suffer from tolerability-driven dropouts. Roche's $2.7 billion acquisition of the developer signals significant confidence in the programme.
Evidence Reviews
Timelines
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
