Muscle-sparing Drug Could Change What the Body Loses on Weight-Loss Jabs

A drug designed to protect muscle has helped people on weight-loss medication keep more of their lean body mass while still losing fat, according to results from an early clinical trial.

The findings, from the Phase 2 EMBRAZE trial, were published in the journal Nature Medicine on 8 June. They concern apitegromab, an investigational antibody made by the US biopharmaceutical company Scholar Rock, given alongside the weight-loss drug tirzepatide.

Tirzepatide and similar GLP-1 medications are widely used for weight management, but rapid weight loss with these drugs can include the loss of lean body mass as well as fat. Lean mass covers skeletal muscle along with organs, water and other non-fat tissue. Researchers have been investigating ways to protect it because losing muscle may affect strength, mobility and long-term metabolic health.

Apitegromab works by selectively blocking the activation of myostatin, a protein that limits muscle growth. The trial tested whether adding it to tirzepatide could reduce the lean mass lost during treatment.

The study enrolled 102 adults with overweight or obesity and split them into two equal groups. All participants received tirzepatide, titrated to a maximum dose of 15 mg weekly. One group also received apitegromab at 10 mg/kg by intravenous infusion every four weeks, while the other received a placebo infusion on the same schedule. The trial was randomised, double-blind and ran for 24 weeks. Most participants were women.

At 24 weeks, total weight loss was broadly similar between the two groups, but the make-up of that loss differed. Participants on apitegromab lost about 1.9 kg less lean mass than those on placebo, a result the researchers described as a 54.9% retention of lean mass relative to placebo. The finding was statistically significant.

Lean mass accounted for 14.6% of total weight loss in the apitegromab group, compared with 30.2% in the placebo group. Fat made up 85.3% of the loss with apitegromab and 69.5% without it.

The trial did not find a clear difference between the groups in grip strength or sit-to-stand tests, both measures of physical function.

Researchers responding to the study through the Science Media Centre noted that lean mass is used as a proxy for muscle but does not measure it directly. As one commentator put it, "Lean mass is often used as a proxy for muscle mass, however it's important to note that is does not measure muscle directly, and the authors do acknowledge this in the study." The lack of a strength difference, the commentary added, "may be due to the relatively short trial, or it could be because lean mass is not accurately capturing muscle mass in this study."

Adverse events occurred at similar rates in both groups, in 39 of 51 participants (76%) on apitegromab and 36 of 51 (71%) on placebo. Serious adverse events were rare and balanced, affecting one participant in each group. The authors described the combination as well tolerated in this proof-of-concept setting.

Apitegromab is not approved for weight management by the FDA or any other regulator. Scholar Rock's main development work with the drug has been in spinal muscular atrophy. In this trial it was given only by intravenous infusion in a research setting.

The authors described EMBRAZE as a proof-of-concept study. They said it demonstrated that targeting myostatin could preserve lean mass alongside tirzepatide, but noted that further and longer trials would be needed to establish whether preserving lean mass leads to meaningful improvements in strength, mobility or long-term health.