Medicine: Protecting muscle during weight-loss treatment (Nature Medicine)

A drug called apitegromab may help to preserve lean body mass during weight loss with tirzepatide, a GLP-1 receptor agonist, according to a phase 2 clinical trial published in Nature Medicine. The findings suggest that blocking a protein that limits muscle growth may improve patient weight loss outcomes by reducing the loss of lean body mass.

GLP-1 receptor agonists such as tirzepatide can help people lose a substantial amount of body weight. However, some of this weight loss can come from lean body mass. Lean body mass is made up mostly of skeletal muscle, which is important for strength, general health, metabolism, and physical activity. Apitegromab is a drug designed to block myostatin, a protein involved in the breakdown of skeletal muscle.

Richard Pratley and colleagues tested apitegromab in a randomised, double-blind, placebo-controlled phase 2 trial. The trial included 102 adults with overweight or obesity, who received either tirzepatide plus apitegromab or tirzepatide plus a placebo for 24 weeks. By the end of the study, total weight loss was similar between the two groups, but people who had received apitegromab lost 1.9 kg less lean mass than those who received the placebo, which represents a 54.9% greater retention of lean mass. Lean mass made up 14.6% of total weight loss in the apitegromab group, compared with 30.2% in the placebo group. Apitegromab was generally well tolerated, with similar rates of adverse events between the treatment groups including 39 of 51 (76%) of apitegromab subjects experiencing any adverse event, compared to 36 of 51 (71%) in the placebo group.

The authors suggest that apitegromab may help to preserve lean mass during tirzepatide treatment and could help to improve the composition of weight loss. However, they note that the trial was relatively small, included more than 80% female participants, and excluded people with significant cardiometabolic conditions, including diabetes.

• Article
• Open access
• Published: 08 June 2026

Pratley, R.E., Denham, D.S., Trivedi, R. et al. Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial. Nat Med (2026). https://doi.org/10.1038/s41591-026-04440-4

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