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Lancet

Trevogrumab reduced nonfat tissue loss in adults with obesity

At 26 weeks, lean mass fell 6.6% with semaglutide plus placebo; adding 200 mg trevogrumab reduced that decline by 3.1 percentage points.

Paper by Ofri Mosenzon, Julio Rosenstock, José G Raya, +11 more authorsBoaz Hirshberg
Skeletal muscle with full dark blue-green fibers tapering into thin gray strands, surrounded by fat cells and a forked antibody.

Our read

Interventions
Studied:
Randomized trial in 599 adults with obesity, 26 weeks, against semaglutide plus placebo (Double-blind, placebo-controlled, multicenter, registered NCT06299098)
What changed:
Adding 200 mg trevogrumab to semaglutide reduced nonfat tissue loss by 3.1 percentage points versus semaglutide plus placebo
The catch:
Regeneron Pharmaceuticals, Inc. funded the trial
In the record:
One of 7 papers on trevogrumab on record: 3 with results in people.

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
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Adults aged 18–80 with obesity joined a two-part, phase 2, double-blind, placebo-controlled randomized trial enrolling 975 people: 627 women and 348 men. In its 26-week portion, semaglutide was titrated to 2.4 mg weekly, alongside placebo, weekly trevogrumab at 200 or 400 mg, or 400 mg trevogrumab plus intravenous garetosmab at 10 mg/kg every four weeks. Adding both antibodies reduced loss of lean mass—nonfat tissue—by 4.5 percentage points versus semaglutide plus placebo.

The two-antibody group had serious adverse events in 14 of 149 participants (9%) and treatment discontinuations in 48 (32%). Muscle spasms occurred in 61 of 149 (41%), versus 23 of 299 (8%) receiving trevogrumab alone and seven of 151 (5%) receiving semaglutide plus placebo. Two deaths occurred in the two-antibody group; no causal association with treatment was identified.

Why it matters

For healthy aging, the relevant question is whether obesity treatment can reduce fat while preserving muscle.

Caveats

Changes in lean mass do not establish whether muscle strength was preserved, and all participants had obesity. Trevogrumab alone had a safety profile similar to semaglutide plus placebo; gastrointestinal adverse events were the most common across groups.

Where the evidence stands

Trevogrumab

Humans: a single group. Cells, worms or flies and mice: nothing yet.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

  • 3 independent labs
  • 1 finding against
  • 2 trials
  • 2 of 2 trials sponsored by its developers

Semaglutide

Cells, mice and humans: replicated by independent labs. Worms or flies: nothing yet.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

No results posted: trials that ended over a year ago with no results on ClinicalTrials.gov and no paper reporting them.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

  • 432 independent labs in 62 countries
  • 105 findings against
  • 398 trials, 94 with no results posted
  • Funders: Novo Nordisk and others
  • 387 of 1,578 findings with company ties
  • 214 of 398 trials sponsored by its developers

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The paper

Trevogrumab (anti-GDF8) with or without garetosmab (anti-activin A) for prevention of muscle loss during semaglutide-induced weight reduction in people with obesity (COURAGE): a two-part, phase 2, double-blind, placebo-controlled, randomised trial

Ofri Mosenzon, Julio Rosenstock, José G Raya, +11 more authorsBoaz Hirshberg

Lancet, Nov 2026

doi.org/10.1016/s0140-6736(26)01953-7

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