A person can lose 30 kilograms and end up weaker than before. Not from a lack of discipline, but because new GLP-1 weight-loss drugs are so efficient that they break down muscle alongside fat. In some patients, one in three kilograms lost comes not from fat deposits but from skeletal muscle. A Phase-2 trial published in Nature Medicine in June 2026 now points to a way to shift that ratio without slowing weight loss.
The problem with 60 million users
GLP-1 agonists like tirzepatide (Zepbound) and semaglutide (Ozempic, Wegovy) have fundamentally changed obesity treatment. More than 60 million people worldwide now take these medications. They reduce body fat by 15 to 25 percent of starting weight and demonstrably lower the risk of cardiovascular disease and type-2 diabetes.
The downside: roughly 30 percent of weight lost comes from lean body mass, primarily skeletal muscle. For someone losing 15 kilograms, that calculates to 4.5 kilograms of muscle. Dr. Brendan Gabriel from the University of Aberdeen, who commented on the study for the Science Media Centre, puts this in perspective: "There is no clear evidence that weight-loss medications cause greater muscle loss than conventional dieting." Muscle loss is therefore a side effect of weight loss generally, not a specific problem of GLP-1 injections. Yet it carries medical weight: muscle wasting raises fall risk, lowers basal metabolic rate, and can lead to clinical sarcopenia in older patients.
Myostatin: Nature's growth brake
The protein myostatin was identified in the 1990s when researchers examined cattle with unusually high muscle mass. These animals carried a mutation that inactivated myostatin. Without myostatin, muscle tissue grows largely unchecked. The protein is thus a natural limiter of muscle growth, preventing the body from continuously investing energy in excessive musculature.
Apitegromab is a monoclonal antibody that blocks myostatin. Developed by US pharmaceutical firm Scholar Rock initially for spinal muscular atrophy, a rare genetic disorder, its use in GLP-1 patients would be different: not building new muscle, but preserving what would otherwise remain.
The EMBRAZE trial: what 102 patients showed
EMBRAZE was a randomized, double-blind, placebo-controlled Phase-2 study. Between June and September 2024, 102 adults with overweight or obesity were split 1:1 into two groups: tirzepatide plus apitegromab (10 mg/kg intravenously every four weeks) or tirzepatide plus placebo. Treatment ran for 24 weeks. Nature Medicine published results in June 2026.
Scholar Rock's core finding: the apitegromab group lost 1.9 kilograms less muscle mass than the placebo group with nearly identical total weight loss, which Scholar Rock quantifies as 54.9 percent retention of muscle mass versus placebo. Concretely, 14.6 percent of total weight loss in the apitegromab group came from muscle, compared to 30.2 percent in the control group. Put another way: 85 percent fat and 15 percent muscle versus 70 percent fat and 30 percent muscle. The frequency of adverse events was comparable in both groups: 76 percent in the apitegromab group, 71 percent with placebo.
Munich researches the field, but approval is years away
Prof. Henning Wackerhage at the Technical University of Munich's Chair of Sports Biology called myostatin inhibitors a promising approach to limit muscle loss on weight-loss injections in an interview with Die Zeit. His research group HyperMet at TU Munich received 4.5 million euros in funding from the German Research Foundation for studies on muscle building and metabolic health.
Gabriel from the Science Media Centre urged caution: EMBRAZE was a Phase-2 study with 102 participants and 24 weeks of follow-up. Whether results hold in larger populations over longer treatment periods remains unknown. Long-term data on apitegromab combined with GLP-1 agonists are entirely absent. The clinical relevance of a 1.9-kilogram difference in muscle mass—whether this difference translates to measurable strength, mobility, or reduced fall rates—has not yet been demonstrated.
Neither the FDA nor the EMA has approved apitegromab for use in GLP-1 patients. Scholar Rock has announced Phase-3 trials without naming specific timelines.
The approval question and what follows
The open question is not purely scientific in nature. Apitegromab is infused intravenously every four weeks for spinal muscular atrophy. At that indication, a year of treatment costs six figures. If apitegromab came to market for GLP-1 patients as an add-on treatment, it would create a combination therapy expensive in both components. GLP-1 agonists currently cost 150 to 400 euros monthly in Germany without insurance coverage.
In Germany, statutory health insurance has covered weight-loss injections only in very narrow exceptions, because the Federal Health Ministry has not yet classified them as a benefit. An additional substance for muscle preservation during an already uninsured treatment would initially apply only to self-payers. The Joint Federal Committee and insurers would only weigh coverage if approval were granted.
Phase 3 comes after Phase 2, and EMA approval would be realistic only in three to four years at earliest. For millions of GLP-1 users today, that means: anyone who wants to preserve muscle mass during a weight-loss injection treatment has only one evidence-based option so far—strength training.