Regeneron reported on 1 October 2026 that trevogrumab, an investigational anti-myostatin (anti-GDF8) monoclonal antibody, reduced the lean-mass loss associated with semaglutide 2.4 mg in adults with obesity. The Phase 2 COURAGE results were presented at the European Association for the Study of Diabetes (EASD) Annual Meeting and are in press with The Lancet. Trevogrumab holds no marketing authorisation in the UK or elsewhere, and no anti-myostatin agent is available as a medicine. What follows is a research readout.
Trevogrumab is an antibody, not a peptide, and this article would not ordinarily sit in a peptide reference. It does so because it is the first agent in the myostatin pathway to report a muscle-preservation endpoint beside a GLP-1 receptor agonist — and the earlier attempts in that pathway were peptide and fusion-protein constructs.
What COURAGE measured
The trial's lower-dose portion compared trevogrumab 25 mg or 75 mg, added to semaglutide 2.4 mg, against semaglutide alone over 52 weeks. The primary endpoint was lean-mass preservation. By DXA, the placebo-plus-semaglutide arm lost 6.7% of lean mass at 26 weeks and 7.3% at 52 weeks. The trevogrumab arms lost less: 4.7% at 26 weeks (29.9% preservation relative to placebo) and 5.8% at 52 weeks (20.5% preservation) at 25 mg; 3.3% at 26 weeks (50.7% preservation) and 4.2% at 52 weeks (42.5% preservation) at 75 mg.
Lower-dose trevogrumab did not meaningfully increase the weight loss achieved with semaglutide alone. Regeneron reports that the greatest loss of lean mass occurred during the first six months, the period of most rapid weight loss.
The MRI substudy
In a predefined MRI substudy, trevogrumab preserved almost 70% of the thigh-muscle volume that would otherwise have been lost with semaglutide alone. A pre-specified subgroup analysis found that participants meeting the low-lean-mass component of the sarcopenia definition at baseline lost more lean mass on semaglutide alone, and showed numerically greater preservation when trevogrumab was added.
Safety as reported
At least one adverse event was reported in 77% of participants receiving trevogrumab, against 82% on placebo. Events occurring in 10% or more of participants were nausea, constipation, diarrhoea and vomiting — a profile that overlaps with the GLP-1 arm rather than departing from it. This is a 52-week Phase 2 tolerability readout, not a long-term safety dataset.
The peptide attempts that came first
Myostatin — growth and differentiation factor 8 (GDF-8) — is a TGF-beta superfamily member that negatively regulates skeletal muscle mass; the 1997 knockout work in mice established that removing it increases muscle. The first clinical attempts to exploit that pathway were peptide and fusion-protein approaches.
ACE-031 is an activin-receptor type IIB (ActRIIB) ligand trap, a fusion protein built to sequester myostatin and related ligands. It reached a Phase 2 trial in Duchenne muscular dystrophy (NCT01099761) and was terminated over safety findings, including epistaxis and telangiectasia. Follistatin-344, a natural myostatin antagonist, has been investigated largely preclinically and in early gene-therapy work; it has no controlled human muscle-preservation readout and no UK marketing authorisation. Neither construct delivered the endpoint trevogrumab has now reported.
That inversion is the point of interest. In the incretin field, peptides are the medicines and antibodies are the challengers. In the myostatin field it is currently the reverse: the peptide attempts stopped at Phase 2, and an antibody is the first to show lean-mass preservation. That says something about the pathway — sequestering a circulating ligand over a year appears easier to dose and to tolerate than the earlier constructs were — and something about how a class's evidence can be built by a different modality.
What this does and does not show
The readout is Phase 2, with surrogate endpoints: lean mass measured by DXA and by MRI. Lean mass is not the same as muscle function, and the trial was not powered to detect a difference in strength or physical performance. The comparisons are relative percentages within a single trial, and the confidence intervals for the 25 mg and 75 mg arms overlap. Regeneron has said it plans a further Phase 2 trial in older adults with obesity and reduced muscle mass or strength. Until that reports, the proposition that preserving lean mass during GLP-1 therapy changes clinical outcomes is a hypothesis, not a finding.
Nothing here changes the UK position on any GLP-1 medicine. Semaglutide is authorised in the UK for type 2 diabetes and for weight management; a combination with an anti-myostatin antibody is investigational and unlicensed.
The UK legal position
Under the Medicines Act 1968 and the Human Medicines Regulations 2012, whether a product is a medicine is determined by the MHRA case by case, by reference to its presentation and function. Trevogrumab, ACE-031 and follistatin-344 hold no UK marketing authorisation, and supplying them for human use would fall outside the licensed supply chain. Research peptides sold for laboratory use are a separate question: the MHRA has said it disregards 'research purposes' claims where they are being used as an attempt to avoid medicines regulation. Research use only, in the UK, is a laboratory framing — not a route to human use.
This article is AI-researched and editorially reviewed. It is provided for research and educational purposes only and is not medical advice. Research peptides are not licensed for human consumption in the UK.