Regeneron's headline for its COURAGE trial reads: lower-dose trevogrumab "preserved almost 70% of the thigh muscle" that people lose on semaglutide. Elsewhere in the same press release, the whole-body measure of lean mass shows preservation of 20% to 43% at 52 weeks.

Both numbers are correct. They answer different questions, and anyone considering a GLP-1 drug should know which one they are reading.

What did the trial test?

COURAGE was a Phase 2 trial in adults with obesity (BMI of 30 or more). The lower-dose portion gave semaglutide 2.4 mg to everyone for 52 weeks and added either trevogrumab 25 mg, trevogrumab 75 mg or placebo. Trevogrumab is an antibody that blocks myostatin, a protein that limits muscle growth. The idea is to keep muscle while the weight comes off.

Regeneron announced the results on October 1, 2026, from the European Association for the Study of Diabetes meeting, and says the paper is in press at The Lancet.

Do the two muscle measures agree?

Whole-body lean mass (DXA scan)Thigh muscle (MRI substudy)

Source: Regeneron press release, Phase 2 COURAGE trial, October 1, 2026. Preservation is relative to the loss in the placebo plus semaglutide arm. The MRI substudy covers participants with evaluable scans; the press release does not state how many.

View data

arm	dxa	mri
25 mg, 26 weeks	29.9	63.6
25 mg, 52 weeks	20.5	71.8
75 mg, 26 weeks	50.7	72.7
75 mg, 52 weeks	42.5	68.9

The two measures look at different things.

Lean mass by DXA is a whole-body scan. Lean mass is everything that is not fat or bone, so it includes muscle, organs, water and connective tissue. With semaglutide alone, participants lost 7.3% of lean mass at 52 weeks. With trevogrumab 25 mg they lost 5.8%, and with 75 mg they lost 4.2%. That is 20.5% and 42.5% less loss than on semaglutide alone.

Thigh muscle by MRI looks at one body region in a substudy of people with evaluable scans. Lower-dose trevogrumab preserved 71.8% (25 mg) and 68.9% (75 mg) of the thigh muscle lost on semaglutide alone at 52 weeks.

Neither is wrong. MRI of a specific muscle is more precise about muscle, but it covers one region and a subset of participants. DXA covers the whole body but cannot tell muscle from other lean tissue. The press release's headline uses the more favourable of the two.

What happened to weight and safety?

Trevogrumab did not meaningfully increase the weight lost with semaglutide. The effect it was designed for, changing the composition of the weight lost, is the only effect reported. The release gives no weight-loss percentages.

Adverse events were reported by 77% of participants taking the combination and 82% of those taking placebo with semaglutide. The most common were nausea, constipation, diarrhea and vomiting, which are typical of semaglutide itself. The release calls the lower doses generally well tolerated.

What we still do not know

The press release does not state the number of participants in each arm or in the MRI substudy. Without it we cannot put a confidence interval on any of the percentages above. It reports amounts of muscle, not strength or physical function, so we do not know whether keeping more muscle changes what people can do.

Regeneron plans a further Phase 2 trial in older adults with obesity and low muscle mass or strength. That is the population where muscle loss matters most, and the answer there is the one to watch.

Why does this matter beyond one trial?

GLP-1 drugs are a very large market. Eli Lilly's Mounjaro and Zepbound earned $14.9 billion in the second quarter of 2026 (see our briefing), and the question of what kind of weight is lost is a question about millions of patients. A drug that only changes the composition of weight loss would be an add-on to those products, not a replacement.

Sources

1. Regeneron, Phase 2 COURAGE trial confirms trevogrumab prevents lean mass and muscle loss during GLP-1 receptor agonist-induced weight loss, October 1, 2026.
2. Eli Lilly, second-quarter 2026 earnings release: Mounjaro and Zepbound revenue.
3. Our earlier analyses: The GLP-1 gap is closing from the outside and Two molecules, 65% of Lilly's revenue.