Scholar Rock's EMBRAZE data put a number on drug-assisted lean mass preservation

Scholar Rock has reported the fullest randomized data yet on a question that has followed GLP-1 medications since they became widely used: how much of the weight lost on these drugs is muscle, and can that be prevented with another drug. The company's phase 2 EMBRAZE trial, now published in Nature Medicine, found that adding the investigational myostatin inhibitor apitegromab to tirzepatide preserved 54.9% more relative lean mass over 24 weeks than tirzepatide plus placebo, while total weight loss was similar between the two groups ^[1].

The trial enrolled 102 participants and ran for 24 weeks, comparing tirzepatide plus apitegromab against tirzepatide plus placebo in a randomized, double-blind, placebo-controlled design ^[1]. Tirzepatide is the active ingredient in Mounjaro and Zepbound. Apitegromab works differently than a GLP-1 drug: it targets pro-myostatin and the latent myostatin complex, blocking activation of a protein that normally acts as a natural brake on skeletal muscle growth, which in principle allows more muscle protein synthesis relative to breakdown even while a person is losing weight overall ^[1].

Apitegromab is not a new molecule. It already has a positive phase 3 result in spinal muscular atrophy, giving the drug an established safety record before this obesity-focused testing began ^[1]. Its regulatory path has not been entirely smooth, though the issue has been about manufacturing rather than the drug's biology: the FDA issued a Complete Response Letter in September 2025 concerning the third-party facility that handles fill-finish operations, not apitegromab itself. Following a resubmission and a change of facility, the FDA's action date is now set for September 30, 2026 ^[1].

Apitegromab is one of several drugs being tested against the same biological target, known as the myostatin-activin axis, by different companies. Others in development include bimagrumab, trevogrumab, and taldefgrobep alfa, each blocking the pathway at a slightly different point and each at an earlier or differently paced stage of testing ^[1]. EMBRAZE is the most concrete randomized evidence among them to date that this approach can meaningfully change body composition outcomes during GLP-1 treatment.

Why it matters for patients

Loss of lean mass, which includes muscle, is a recognized side effect of substantial weight loss on GLP-1 medications, and it has been a source of concern for patients and clinicians alike. The EMBRAZE result is notable because it puts an actual number on how much that loss can be reduced with an added drug in a controlled trial, rather than relying on estimates or observational data ^[1].

That said, this combination is not something patients can currently be prescribed. Apitegromab plus tirzepatide remains investigational and is not approved for weight management ^[1]. The trial was also relatively small, at 102 participants, and ran only 24 weeks, so longer-term effects on strength, function, and durability of the lean mass benefit are not yet established from this data alone ^[1]. Whether this translates into meaningful differences in strength or physical function, and whether the benefit holds up over longer treatment periods, is not addressed in the sources here.

What happens next

The FDA's action date tied to apitegromab's manufacturing resubmission is September 30, 2026, though that review concerns the drug's existing spinal muscular atrophy approval pathway rather than a weight-management use ^[1]. A path toward approval for muscle preservation alongside a GLP-1 drug specifically would require further trials beyond EMBRAZE, and no timeline for that step is given in the available reporting.