An experimental antibody cut lean-muscle loss roughly in half for people taking the weight-loss drug tirzepatide, according to results from a placebo-controlled trial published this summer, the latest evidence that pairing GLP-1-class medications with a muscle-preserving drug could address one of the treatments' most persistent side effects.
GLP-1 receptor agonists and related drugs, including tirzepatide and semaglutide, can produce substantial weight loss, but researchers have increasingly flagged that a meaningful share of what patients shed is lean mass — muscle, not just fat — raising concerns about strength and metabolic health, especially in older adults. The new trial tested whether blocking myostatin, a protein that limits muscle growth, could offset that loss without blunting the drugs' fat-loss benefits.
How the trial was designed
In the study, published June 8 in Nature Medicine, 102 adults with overweight or obesity were randomly assigned to receive weekly tirzepatide injections for 24 weeks alongside either monthly infusions of apitegromab, an antibody that selectively blocks myostatin activation, or a placebo infusion. Apitegromab, developed by Scholar Rock, had previously been tested as a treatment for spinal muscular atrophy; this trial, dubbed EMBRAZE, examined it for the first time as a companion to GLP-1-driven weight loss.
The two groups lost comparable amounts of total body weight, but their body composition diverged sharply. Lean mass accounted for only about 15 percent of total weight lost in the apitegromab group, compared with roughly 30 percent in the placebo group — meaning participants on the antibody lost about half as much muscle for a similar amount of overall weight loss, according to coverage of the results in Science News. Participants receiving apitegromab also showed modestly better grip strength and leg-strength scores than those on placebo. Rates of adverse events were similar between the two groups, and serious adverse events were balanced, with one recorded in each arm.
Study coauthor Richard Pratley of the AdventHealth Translational Research Institute in Orlando framed the approach as part of a broader move toward personalizing obesity treatment rather than relying on a single drug for every patient.
The right drug for the right patient at the right time.
Richard Pratley, AdventHealth Translational Research Institute, study coauthor
Outside researchers, including Randy Seeley of the University of Michigan Medical School, noted the results add to a growing body of evidence — including a separate Regeneron-sponsored trial of a different myostatin-targeting antibody paired with semaglutide — that muscle preservation during GLP-1 treatment is achievable. Apitegromab itself remains unapproved by the Food and Drug Administration for this use and, for now, is only available by intravenous infusion, so it is not something patients on tirzepatide or semaglutide can access today. Researchers say larger, longer trials will be needed before any such combination could reach the millions of people currently on GLP-1 drugs.