Apitegromab plus tirzepatide limits muscle loss in Phase 2 EMBRAZE trial

A Phase 2 trial called EMBRAZE has produced the clearest evidence yet that the muscle loss that can come with GLP-1 treatment might be limited by adding a second drug. The results, published in Nature Medicine, tested apitegromab in combination with tirzepatide, the molecule sold as Mounjaro and Zepbound ^[1][2].

Across GLP-1 trials, lean mass has accounted for roughly 25% to 40% of the total weight participants lost ^[1][2]. Lean mass includes skeletal muscle, and that range is the main reason companies have been testing compounds meant to protect it. Whether preserving lean mass during treatment changes how patients feel or function has not been established by the EMBRAZE results reported so far.

EMBRAZE is a Phase 2 study, an earlier and smaller stage of testing than the Phase 3 trials regulators rely on for approval. Key details have not been disclosed: how many people took part, how long they were treated, what doses were used, and how much lean mass was preserved. The trial's full design and its inclusion criteria have not been reported.

No drug is approved in the United States to protect muscle during GLP-1 treatment, and apitegromab is not available as a prescribed medicine for this use ^[1][2]. The combination tested in EMBRAZE exists only inside a clinical trial program.

The result arrives as GLP-1 use keeps widening. On 10 August 2026, the UK medicines regulator authorised orforglipron, sold as Foundayo, for weight management and type 2 diabetes, making the UK the first country in Europe to approve the tablet ^[1]. Orforglipron is a small-molecule GLP-1 receptor agonist rather than a peptide, which is why it can be taken by mouth without the fasting window that oral semaglutide requires ^[1]. More people on GLP-1 medicines for longer periods is part of what makes muscle-loss data matter, and the same August roundup recorded continued movement across obesity trials and regulatory reviews ^[1][2].

Why it matters for patients

People taking semaglutide (Ozempic, Wegovy, Rybelsus) or tirzepatide (Mounjaro, Zepbound) lose both fat and lean mass. The 25% to 40% figure means that for every 10 pounds lost in the trials reviewed, roughly 2.5 to 4 pounds came from lean tissue ^[1][2]. Lean tissue includes the muscle used for standing, walking and gripping.

What EMBRAZE does not yet show is whether adding apitegromab changes anything a patient would notice, such as strength, physical function or the ability to stay on treatment. Phase 2 results are not proof that a combination improves health outcomes.

Nothing about the EMBRAZE finding changes what is currently prescribed. There is no approved muscle-protecting drug to add to a GLP-1 regimen, no approved dosing for one, and no evidence reported here about how a second drug would affect side effects, injection burden or cost. Anyone weighing a clinical trial can ask their clinician what studies are enrolling and what participation involves, but no recommendation follows from these results.

What happens next

EMBRAZE is a Phase 2 trial, so a larger Phase 3 program would normally be needed before any regulatory review. A timeline for further apitegromab trials in this setting has not been reported, and no submission to the US Food and Drug Administration for this use has been announced ^[1][2].

In the wider GLP-1 field, a handful of dated milestones remain open. The FDA's decision on CagriSema for weight management is expected in late 2026, and Novo Nordisk has guided to the start of a higher-dose CagriSema trial in the second half of 2026 ^[1]. Eli Lilly plans to submit retatrutide to the FDA in the first quarter of 2027 ^[1]. None of those programs addresses muscle preservation directly.