BYM338
Evidence Grade C — Moderate human evidence. 74 published studies, 52 human. 12 registered clinical trials.
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.
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.
Safety, Pharmacokinetics and Efficacy of Bimagrumab in Overweight and Obese Patients With Type 2 Diabetes
An Extension Study of the Efficacy, Safety and Tolerability of BYM338 (Bimagrumab) in Patients With Sporadic Inclusion Body Myositis Who Previously Participated in the Core Study CBYM338B2203
A 24-week Off-drug Extension Study in Sarcopenic Elderly Who Completed Treatment in the 6-month Core Study
Dose Range Finding Study of Bimagrumab in Sarcopenia
Study of Efficacy and Safety of Bimagrumab in Patients After Hip Fracture Surgery
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.
Liraglutide is marketed as Victoza for type 2 diabetes (approved 2010) and Saxenda for weight management (approved 2014). The LEADER trial, involving over 9,300 patients followed for nearly four years, established that liraglutide reduced the risk of major cardiovascular events by 13% — a landmark finding that helped establish GLP-1 treatments as a class with heart benefits. Saxenda is also approved for adolescents aged 12 and older. While historically significant, liraglutide has been substantially surpassed by newer agents. In a direct comparison, semaglutide achieved 15.8% weight loss compared to liraglutide's 6.4%. Liraglutide remains relevant as a lower-intensity option and as a benchmark against which newer treatments are measured. It has over a decade of real-world safety data, making it one of the best-understood medications in this class.
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.
HGH Fragment 176-191 has no marketing authorisation. A Phase IIa trial in obesity (approximately 300 patients) failed to demonstrate statistically significant weight loss at any dose tested. The clinical development programme was discontinued. The disconnect between animal data (which showed significant fat reduction in obese mice) and the failed human trial is the defining feature of this compound's development history. Products available through unregulated channels lack pharmaceutical quality assurance. The failed Phase II trial represents the highest level of clinical evidence available.
