An antibody preserves muscle mass during weight loss
Weight loss induced by treatments such as tirzepatide is often accompanied by a reduction in muscle mass, which can harm health and physical function. A recent study evaluated the effectiveness of an antibody called apitegromab in limiting this muscle loss. This antibody works by specifically blocking the activation of myostatin, a protein that regulates muscle degradation. By inhibiting this protein, apitegromab promotes the increase and preservation of muscle mass.
The study involved 102 overweight or obese adults, divided into two groups receiving either tirzepatide combined with apitegromab or tirzepatide with a placebo. After 24 weeks, participants treated with apitegromab lost an average of 1.9 kg less muscle mass than those on placebo, while showing a similar total weight loss. This represents a preservation of nearly 55% of muscle mass compared to the placebo group. Apitegromab and latent myostatin concentrations increased gradually, reaching a plateau after about 16 weeks, confirming the treatment’s effectiveness.
Adverse effects were comparable between the two groups, with mainly mild and transient incidents. No serious effects related to apitegromab were reported. The results show that apitegromab, by selectively targeting myostatin, preserves muscle mass without compromising fat loss, offering a promising approach for people undergoing obesity treatment.
Myostatin is a natural protein that limits muscle growth. Its selective inhibition by apitegromab had already demonstrated benefits in animal models and in patients with spinal muscular atrophy, reinforcing its therapeutic potential. Participants saw their fat loss represent a larger portion of their total weight loss, which is beneficial for metabolic health.
This study confirms that apitegromab, by acting on a well-established biological mechanism, can mitigate muscle loss associated with weight loss treatments while maintaining good tolerance. The results pave the way for new strategies to improve body composition during drug-induced diets.
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Original Publication
DOI: https://doi.org/10.1038/s41591-026-04440-4
Title: Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial
Journal: Nature Medicine
Publisher: Springer Science and Business Media LLC
Authors: Richard E. Pratley; Douglas Scott Denham; Rupal Trivedi; Elaine Watkins; Lisa Connery; Jennifer Barnes; Dongzi Yu; Janet Hong; Christopher Simard; Kimberly Umans; Lan Liu; Giridhar S. Tirucherai; Jing L. Marantz