Trevogrumab is an experimental drug being tested to limit lean-mass loss during weight loss on semaglutide. Lean mass means tissue that isn't fat or bone, including muscle, organs and water. New COURAGE trial findings report a smaller decline when the drugs were combined.
That is encouraging, but a better scan doesn't automatically mean stronger muscles. Trevogrumab remains investigational, meaning it is still being tested, and is not approved anywhere.
What happened in the trevogrumab COURAGE trial
As of September 30, 2026, the day this article was written, the posted COURAGE dose-finding abstract reports less lean-mass loss with trevogrumab added to semaglutide. It belongs to this week's European Association for the Study of Diabetes meeting, known as EASD.
COURAGE is a phase 2 trial, an early study of a treatment's effects and safety. Its Part C enrolled 376 adults with obesity without type 2 diabetes. Everyone received semaglutide; groups also received placebo, an inactive comparison treatment, or weekly trevogrumab at 25 mg or 75 mg.
The public abstract reports these changes after 26 weeks:
| Treatment studied | Lean-mass change from the starting amount |
|---|---|
| Semaglutide plus placebo | −6.8% |
| Semaglutide plus trevogrumab 25 mg | −4.9% |
| Semaglutide plus trevogrumab 75 mg | −3.4% |
Those are 26-week figures. The 52-week results were published in The Lancet on September 30, and a Medical Xpress report on the paper says lean mass fell 7.3% with semaglutide plus placebo by week 52. Against that, the 75 mg combination's difference (+3.1 percentage points) was statistically significant; the 25 mg difference (+1.5) was not.
Researchers measured tissue with DXA, a low-dose X-ray scan that separates fat, bone and lean tissue. The 75 mg group's decline was about half the comparison group's decline. That is a difference between trial averages, not a forecast for someone starting treatment.
The percentages describe changes in lean mass itself. They aren't percentages of total weight lost, which answers a different question.
What the findings mean for someone on semaglutide
The useful question is whether weight loss can come with less loss of tissue the body needs. COURAGE brings that question into a controlled human study. It doesn't establish that everyone on semaglutide needs another medication.
The muscle measurement is worth separating from the lean-tissue measurement. MRI, a scan that uses magnets to show tissue, can examine thigh muscle more directly than DXA.
As of September 30, 2026, the day this article was written, the posted COURAGE MRI abstract reports results from 75 participants. At 26 weeks, the 75 mg combination was associated with 77% less thigh-muscle volume loss than semaglutide alone. The analysis described scan changes without formally testing statistical differences.
That percentage concerns the loss avoided, not the percentage of all muscle retained. It also doesn't establish better walking, strength or balance. Our semaglutide muscle-loss explainer covers the broader evidence behind those distinctions.
How a myostatin inhibitor is meant to help
Myostatin is a protein that acts as a brake on muscle growth. Trevogrumab is an antibody, a lab-made immune protein designed to attach to a specific target. It blocks myostatin's signal. Semaglutide works through GLP-1, a gut-hormone signal involved in appetite and blood sugar.
The idea has some human groundwork. An earlier phase 1 trial, a small initial safety study, enrolled 82 healthy adults. It tested trevogrumab and garetosmab, which blocks another muscle-growth brake called activin A (Gonzalez Trotter and colleagues, Nature Communications, 2025). Most participants were women after menopause.
That study examined muscle size and body composition. It wasn't a trial of semaglutide treatment, so it couldn't settle the weight-loss question COURAGE now asks.
What the news does not mean
Preserving tissue on a scan isn't the same as proving a lasting health benefit. Strength, daily activity and safety over years still matter. A larger muscle measurement alone can't answer all three.
As of September 30, 2026, the day this article was written, the posted 52-week COURAGE abstract describes a separate withdrawal experiment. After semaglutide stopped, participants received trevogrumab 400 mg or placebo for another 26 weeks. Researchers reported lean mass returning to its starting level in the trevogrumab groups; fat also returned after semaglutide stopped. That doesn't establish weight maintenance with the lower 75 mg dose.
The two-drug and three-drug combinations also deserve separate readings. COURAGE's earlier Part B tested semaglutide, trevogrumab and garetosmab together. In its September 17, 2025 release, Regeneron reported more treatment stops and two deaths in that three-drug group.
One death had an undetermined cause in someone with multiple heart-risk factors. The other followed cardiac arrest in someone with heart disease. Regeneron said it had not identified a causal connection to treatment. Those findings concern that combination; they don't prove trevogrumab caused the deaths.
Does this change the muscle question with tirzepatide?
COURAGE studied semaglutide, so its findings cannot establish what adding trevogrumab to tirzepatide would do. Tirzepatide acts on two gut-hormone signals, GIP and GLP-1. Its different design doesn't settle muscle preservation either.
As of September 30, 2026, the day this article was written, the EMBRAZE paper, published June 8, 2026, offers a related caution. This Nature Medicine trial tested a different antibody, apitegromab, with tirzepatide. Participants lost less lean tissue, but researchers reported no notable difference in physical-function tests.
Apitegromab has a separate regulatory story. FDA lists its September 11, 2026 approval for spinal muscular atrophy, an inherited condition that damages the nerves controlling muscles. That indication doesn't cover muscle loss during weight management. Our apitegromab approval explainer covers what that decision means.
What to watch next, and what a visit can address now
As of September 30, 2026, the day this article was written, EASD's official programme lists a dedicated COURAGE session for October 1. The next useful answers concern longer follow-up, older adults and whether scan differences translate into better function. Larger studies also help reveal uncommon side effects.
For someone already considering semaglutide, a visit can address food intake, strength, activity limits and treatment tolerability now. Exercise on semaglutide explains the existing evidence without treating an experimental antibody as part of that plan. The prescriber sets the actual dose.
Through Promise, semaglutide and tirzepatide are dispensed as compounded medications, which is different from an FDA-approved product: the formulations offered here are not FDA-approved. FDA explains that compounded drugs do not undergo its review for safety, effectiveness or quality before marketing.
A licensed provider may still prescribe a compounded formulation; that decision is between you and your doctor. At Promise, a licensed provider reviews every request, and not everyone qualifies.
