In this article16 sections
Two Regeneron antibodies that release the body's brakes on muscle. Added to semaglutide, trevogrumab halved the muscle lost; adding garetosmab as well protected almost all of it, but many people stopped and two died. Neither is approved for weight loss or sold anywhere.
Trevogrumab, also known by its development code REGN1033, is a fully human made by Regeneron that binds and neutralises myostatin, the protein that limits skeletal muscle growth. It is the anti-myostatin arm of Regeneron's obesity programme, tested in the COURAGE trial alongside semaglutide to see whether blocking myostatin can stop the muscle loss that accompanies weight loss. This article sets out what trevogrumab is, why it is paired with garetosmab, what COURAGE reported at 26 weeks and at one year, the side effects arm by arm, and when either could be available. It exists because visitors to our retatrutide page ask about it. Trevogrumab is investigational; ALTA PEPTIDES supplies a research-grade version for laboratory use only and this is not guidance on using anything.
- Trevogrumab (REGN1033) is a fully human monoclonal antibody that binds and neutralises mature myostatin (GDF8). It is a biologic, not a peptide.
- COURAGE is Regeneron's phase 2 trial in adults with obesity: semaglutide 2.4 mg alone, or with trevogrumab 200 mg, trevogrumab 400 mg, or trevogrumab 400 mg plus garetosmab, over a 26-week weight-loss phase.
- At 26 weeks, 33% of semaglutide-induced weight loss was (3.3 kg). Adding trevogrumab cut that to 1.5 kg (lower dose) or 1.9 kg (higher dose); the triplet with garetosmab cut it to 0.9 kg.
- The triplet arm had a substantially higher discontinuation rate and two deaths; Regeneron reported no causal association identified.
- Trevogrumab is investigational, has not been evaluated by any regulator, and is not available outside Regeneron's trials. ALTA PEPTIDES supplies a research-grade version for laboratory use only.
What is trevogrumab?
In shortA Regeneron antibody that blocks myostatin, the body's main brake on muscle growth.
Code name REGN1033.
The main brake on muscle growth.
A large protein, not a peptide.
Not approved anywhere.
From this article.
Myostatin, or GDF8, is made by muscle and signals through the activin type II receptors to hold muscle mass down. Trevogrumab is an IgG antibody raised in Regeneron's VelocImmune mice, which carry humanised antibody genes, and it binds mature myostatin so that it cannot reach the receptor. It does not bind activin A, the related ligand that shares the receptor, which is why Regeneron pairs it with a second antibody, garetosmab, in one arm of COURAGE. Our myostatin inhibitor pillar explains the pathway and where each antibody acts on it.
Trevogrumab's first clinical outing was in sarcopenia, roughly a decade ago: a phase 2 study in around 250 adults aged 70 and over reported small lean mass gains at all three doses without a significant improvement in strength or walking tests, the same pattern as most myostatin antibodies before it. The obesity programme rests on a different premise: not growing muscle in people who have lost it, but keeping muscle in people who are losing weight fast.
Why is it paired with garetosmab?
In shortMuscle has two brakes on the same switch. Blocking both protects more muscle.
- 01Myostatin
Brake no. 1. Trevogrumab blocks it.
- 02Activin A
Brake no. 2. Garetosmab blocks it.
- 03Same receptor
Both brakes press on ActRII.
- 04Block both
More muscle kept, but more side effects.
Mechanism as described in this article.
Myostatin (GDF8) and activin A are two signalling proteins that limit skeletal muscle growth, and both act through the same activin type II receptors on the muscle cell. Trevogrumab (REGN1033) binds mature myostatin; garetosmab binds activin A. Block one ligand and the other can still reach the receptor, which is why myostatin antibodies on their own have tended to produce modest gains. Regeneron's animal work suggested that blocking both together protects muscle more completely, and COURAGE was designed to test that in people losing weight on semaglutide. Our myostatin inhibitor pillar explains the pathway and where each antibody acts on it; our garetosmab article covers garetosmab's own history.
What did the COURAGE trial show?
In shortSame weight lost, but far less of it was muscle. With both antibodies, almost none.
Lean mass as a share of total weight lost, by DXA. Regeneron, 17 Sep 2025.
COURAGE enrolled adults with obesity (BMI of 30 or above) and randomised them to semaglutide 2.4 mg alone, semaglutide with trevogrumab 200 mg, semaglutide with trevogrumab 400 mg, or semaglutide with trevogrumab 400 mg plus garetosmab 10 mg/kg (the "triplet"). The trial is split into a 26-week weight-loss phase and a 26-week maintenance phase in which participants receive trevogrumab 400 mg alone or placebo through week 52. The three primary endpoints, measured at week 26, were percent change in lean mass, fat mass and body weight, with lean and fat mass by scan. Regeneron reported interim results in June 2025 and the complete 26-week analysis as a late-breaking oral presentation at EASD on 17 September 2025.
The four arms analysed comprised 151, 149, 152 and 147 participants respectively. Results from baseline to week 26:
- Semaglutide alone: body weight -10.6%; lean mass -6.5% (-3.3 kg, 33.0% of total weight lost); fat mass -15.7% (-6.7 kg, 67.0%).
- Semaglutide plus trevogrumab 200 mg: body weight -9.9%; lean mass -3.3% (-1.5 kg, 16.8% of loss); fat mass -17.3% (-7.6 kg, 83.2%).
- Semaglutide plus trevogrumab 400 mg: body weight -11.1%; lean mass -3.8% (-1.9 kg, 18.1%); fat mass -19.1% (-8.5 kg, 81.9%).
- Triplet (plus garetosmab): body weight -13.4%; lean mass -2.0% (-0.9 kg, 7.4%); fat mass -27.1% (-11.8 kg, 92.6%).
Regeneron's summary was that trevogrumab "could prevent about half" of the lean mass loss caused by semaglutide, with the lean mass differences against semaglutide alone reaching p<0.001 in all three combination arms (not corrected for multiplicity). Total weight loss was not increased by trevogrumab alone; what changed was the composition, with more fat and less lean tissue in what was lost. The triplet went further on both counts. Numerical improvements in waist circumference, blood pressure, cholesterol, triglycerides and A1C were seen across all groups as secondary and exploratory endpoints.
What happened at one year?
In shortOver a full year, lower doses still cut muscle loss by up to about 40%.
Percent of lean mass lost at 52 weeks. Regeneron, 1 Oct 2026; MRI substudy: about 70% of thigh muscle loss prevented.
Regeneron reported one-year results from a second, lower-dose part of COURAGE on 1 October 2026, presented at EASD 2026 and in press with The Lancet. At 52 weeks, people on semaglutide plus placebo had lost 7.3% of their lean mass; adding the lower trevogrumab dose cut that to 5.8%, and the higher dose to 4.2%, which Regeneron expressed as 20.5% and 42.5% of lean mass loss prevented. An MRI substudy found that about 70% of the thigh muscle otherwise lost on semaglutide was kept (71.8% and 68.9% at the two doses). These are company-reported topline figures; the full paper is pending. Regeneron's stated next step is a new phase 2 in older adults with obesity and low muscle mass, not a .
What are the side effects?
In shortMostly muscle spasms and stomach effects from the semaglutide, usually mild.
Regeneron's release listed the adverse events that occurred in 5% or more of any group: muscle spasms, nausea, constipation, fatigue, diarrhoea, headache, vomiting, gastro-oesophageal reflux, upper respiratory tract infection, nasopharyngitis, urinary tract infection, influenza and COVID-19. Trade coverage of the EASD presentation added injection-site reactions. Most events were mild to moderate. The gastrointestinal events are semaglutide's known profile and appeared across all arms; muscle spasms are the event most consistently attributed to myostatin and activin pathway blockade, and they recur in every trial of this class, including bimagrumab's BELIEVE and RESILIENT trials. Regeneron did not publish a per-arm table of individual event rates in its press materials, so we cannot give a percentage for each event by arm; the figures that were released by arm are the discontinuations and deaths below.
How many people stopped, and the two deaths
In shortAlmost 1 in 3 stopped on the three-drug combination, and two people died. No link to the drugs was found.
Share of each arm stopping for adverse events, COURAGE. Regeneron reported no causal link found for either death.
- Semaglutide alone: 4.6% discontinued for adverse events; no deaths.
- Semaglutide plus trevogrumab 200 mg: 4.7% discontinued; no deaths.
- Semaglutide plus trevogrumab 400 mg: 10.6% discontinued; no deaths.
- Triplet (plus garetosmab 10 mg/kg): 30.9% discontinued; two deaths.
The discontinuation rate roughly doubles from the lower to the higher trevogrumab dose and triples again when garetosmab is added. Regeneron said the triplet "had a substantially higher rate of discontinuations due to tolerability issues and other adverse events". The two deaths were one of undetermined cause in a participant with multiple cardiovascular risk factors, and one from cardiac arrest in a participant with a history of cardiovascular disease. The company stated it had not identified a causal association between treatment and these events. Two deaths in 147 people over 26 weeks in a population with obesity and cardiovascular risk is not, on its own, proof of harm; zero deaths in the other 452 participants is not proof of safety either. It is the kind of signal a phase 2 raises and only a much larger trial can settle, and it is the reason the maintenance phase continues with trevogrumab alone rather than the pair.
When could trevogrumab and garetosmab be available?
In shortNot for obesity for years. Garetosmab is approved only for a rare bone disease.
- Sep 202526-week results
Muscle kept; the triplet hit tolerability problems.
- Aug 2026Garetosmab approved
For a rare bone disease only (FOP), as Pasatru.
- Oct 2026One-year results
Lower doses still protected muscle.
- NextAnother phase 2
In older adults with low muscle mass.
- ~2030+Earliest for obesity
Needs phase 3, then regulators.
From Regeneron releases and this article.
COURAGE ran in two parts. After the 26-week weight-loss phase, participants moved to trevogrumab alone or placebo through week 52, to see whether the antibody holds lean mass while weight is maintained, and a second part tested lower doses over a full year; those one-year results are summarised above. What has not been announced is a phase 3 trial of trevogrumab, alone or with garetosmab, in obesity. Regeneron's next step is another phase 2, in older adults with obesity and low muscle mass. A phase 3 would need to run for at least a year and any submission would follow it, so an approved product for obesity is several years away at best, and our estimate for the class is not before about 2030.
Garetosmab has a separate life. It was approved by the FDA on 19 August 2026 as PASATRU (garetosmab-grts) for adults with fibrodysplasia ossificans progressiva, an ultra-rare bone disorder, after the phase 3 OPTIMA trial. That approval does not extend to obesity, and PASATRU is supplied through a rare-disease infusion programme, not a pharmacy.
How much would they cost?
In shortNo obesity price exists. Garetosmab for the rare bone disease costs about $1.4 million a year.
There is no obesity price for either antibody because there is no obesity product. The only number that exists is for garetosmab in FOP: Regeneron told Managed Healthcare Executive that PASATRU's annual list price is about $1.4 million for a patient of the average trial weight at the 10 mg/kg dose, with a launch range of $693,000 to $2.1 million depending on dose and body weight. That is a price for a disease affecting roughly 900 diagnosed people worldwide and is not a guide to what a muscle-preserving add-on for millions of people on GLP-1 drugs could cost. Trevogrumab has never been priced anywhere. Our UK availability timeline keeps the current status and prices for all four antibodies in one dated table.
Can you buy trevogrumab or garetosmab?
In shortNo. Vials sold under these names are not the real antibodies.
Research-grade versions of these antibodies are sold by specialist reagent suppliers: recombinant monoclonal antibodies made from the published sequences by third-party manufacturers, for laboratory work. They are not the originator companies' products, they are not approved biosimilars, and they are not medicines; identity and purity rest on the manufacturer's certificate of analysis (for an antibody, methods such as SEC-HPLC and SDS-PAGE), which is the first thing to check. ALTA PEPTIDES supplies research-grade bimagrumab, apitegromab, trevogrumab and garetosmab as 150 mg vials under our research use policy, for laboratory research only and never for human use.
How does it compare with retatrutide?
In shortIt isn't a rival. It's tested alongside weight-loss drugs to protect muscle.
Trevogrumab does not cause meaningful weight loss on its own and is not meant to; it is being developed as a companion to GLP-1 drugs. Retatrutide is a GLP-1, and glucagon triple agonist that has completed phase 3 trials for obesity, with weight loss larger than semaglutide's; our phase 3 summary has the numbers. Whether a myostatin antibody would add the same muscle protection to retatrutide as to semaglutide has not been tested, and Regeneron has not announced a phase 3 for the obesity combination. The realistic timeline for any approval in obesity is several years, and it would be a prescription infusion or injection given with a GLP-1 drug, not a product. Our GLP-1 explainer and weight and metabolic category cover what we do supply.
Everything above is the quick version. The sections below go deeper.
What garetosmab adds: the FOP label and LUMINA-1
In shortGaretosmab's own safety record, from its rare-disease trials.
Trevogrumab and garetosmab side effects are searched together because of the triplet, and garetosmab now has a US label that describes its own profile in a different disease. PASATRU, approved for adults with fibrodysplasia ossificans progressiva on 19 August 2026, carries warnings for fetal harm, for skin and soft tissue infections requiring treatment or hospital care, and for nosebleeds requiring medical intervention. Its common adverse reactions are nosebleeds, increased hair growth, abscess and acne, with eyebrow loss, mouth ulcers, folliculitis, nail infection and rash also reported. In the phase 3 OPTIMA trial, skin and soft tissue infections rose with dose (7, 9 and 15 participants on placebo, 3 mg/kg and 10 mg/kg) while nosebleeds did not, and there were no deaths. In the earlier phase 2 LUMINA-1, five of 44 participants died in the open-label period; the investigators judged the deaths unlikely to be related but could not exclude causality. Those are FOP findings in a population with a short life expectancy, but the skin, hair and nosebleed pattern is what activin A blockade looks like in people, and it is reasonable to expect some of it in anyone who receives garetosmab. Our garetosmab article has the full trial record.
Effects beyond muscle: what blocking myostatin and activin can do
In shortThese signals do jobs outside muscle too, which is where side effects come from.
Three effects recur across the class. First, muscle spasms and cramps, seen with trevogrumab, bimagrumab and apitegromab (bimagrumab muscle spasms affected just under one in ten participants in RESILIENT), presumably because muscle that is being told to grow behaves differently. Second, skin and hair changes, most visible with activin A blockade (garetosmab) and with receptor-level blockade (bimagrumab, where acne was common in BELIEVE). Third, bleeding: ACE-031, a soluble ActRIIB receptor that trapped myostatin and activins, was halted in 2011 after nosebleeds, gum bleeding and telangiectasias attributed to it also trapping BMP9 and BMP10, which maintain blood vessels. Single-ligand antibodies such as trevogrumab do not bind those proteins, and COURAGE did not report a bleeding signal, but every trial in the class monitors for it. Our bimagrumab side effects gives the receptor-level antibody's record for comparison, and the pillar article explains the pathway.
What is still not known
In shortLong-term safety, and why the two deaths happened, are open questions.
Trevogrumab has "not been evaluated by any regulatory authority", in Regeneron's words. There is no label, no adverse reaction table reviewed by a regulator, and no safety database beyond the COURAGE population and a sarcopenia phase 2 of around 250 older adults a decade ago. One-year data exist only for the lower-dose part of COURAGE, reported on 1 October 2026 and not yet published in full. Nothing is known about use over years, about people with heart disease (the deaths make that the obvious question), about combination with tirzepatide or retatrutide, or about what happens when the antibody is stopped. For the wider question of how much muscle GLP-1 drugs cost on their own, see muscle loss on GLP-1 peptides; for the current regulatory status of all four antibodies, see the UK availability timeline. ALTA PEPTIDES supplies research-grade versions of these antibodies as laboratory reagents under our research use policy: recombinant antibodies made by a third-party manufacturer, not the products of the originator companies.
What ALTA PEPTIDES supplies
Trevogrumab is a biologic made in cell culture under Regeneron's control and exists only within its trials. It has "not been evaluated by any regulatory authority", in the company's words, and is not licensed anywhere. It is not a peptide and cannot be made by peptide synthesis; research-grade versions are recombinant antibodies made in cell culture. Regeneron's own antibody is not sold, so a research-grade vial is never Regeneron's product; its identity rests on the manufacturer's . ALTA PEPTIDES supplies research-grade versions of these antibodies as laboratory reagents under our research use policy: recombinant antibodies made by a third-party manufacturer, not the products of the originator companies. For the other three antibodies in this class, see our articles on garetosmab, apitegromab and bimagrumab.
Sources
- Regeneron press release, 17 September 2025: "Results from Phase 2 COURAGE Trial Demonstrating Potential to Improve Quality of GLP-1 receptor agonist-induced Weight Loss by Preserving Lean Mass, Presented at EASD" (arm sizes, lean mass, fat mass, body weight, adverse events, deaths).
- Regeneron press release, 2 June 2025: interim results from the phase 2 COURAGE trial (discontinuation rates by arm, as reported in press coverage of the interim analysis).
- ClinicalTrials.gov: phase 2 study of REGN1033 in patients with sarcopenia (design and population of the earlier sarcopenia trial).
- Regeneron press release, 17 September 2025: complete 26-week COURAGE results presented at EASD (adverse events in 5% or more of any group, discontinuations, deaths, statement on causality).
- Regeneron press release, 2 June 2025: interim COURAGE results (discontinuation rates by arm); Medscape, September 2025: EASD coverage of COURAGE (full-population discontinuation rates).
- Regeneron press release, 19 August 2026, and FDA announcement: approval of PASATRU (garetosmab-grts); Medical Daily and Managed Healthcare Executive, August 2026: label warnings and common adverse reactions.
- Regeneron press release, 17 September 2025: phase 3 OPTIMA results (skin and soft tissue infections and nosebleeds by arm, no deaths).
- Di Rocco et al., Nature Medicine, September 2023: LUMINA-1 phase 2 trial of garetosmab in FOP (five deaths in the open-label period).
- Muscular Dystrophy Association, April 2011: ACE-031 trials halted for nosebleeds, gum bleeding and telangiectasias.
- Regeneron press release, 17 September 2025: complete 26-week results from the phase 2 COURAGE trial presented at EASD (arm sizes, body weight, fat and lean mass, discontinuations, deaths).
- Regeneron press release, 2 June 2025: interim COURAGE results (discontinuation rates by arm).
- Regeneron Form 8-K, fourth quarter 2025 results (plan to report additional COURAGE data in 2026); Regeneron press release, 30 July 2026: second quarter 2026 results (pipeline updates, no obesity phase 3 announced).
- EASD 2026 final programme and Medscape EASD 2026 preview: new COURAGE weight and body composition outcomes scheduled for presentation in Milan.
- Regeneron press release, 19 August 2026: FDA approval of PASATRU (garetosmab-grts) for adults with FOP; Managed Healthcare Executive, August 2026: PASATRU list price of about $1.4 million a year, launch range $693,000 to $2.1 million.
Questions people ask
Can you buy trevogrumab?
Not Regeneron's antibody, which exists only inside its clinical trials and has never been licensed. Research-grade trevogrumab, made by a third-party manufacturer, is available as a laboratory reagent for in-vitro research; ALTA PEPTIDES supplies it, not for human use.
What is trevogrumab used for?
It is being studied, not used. The current trial tests whether adding it to semaglutide preserves lean mass during weight loss. An earlier phase 2 in sarcopenia (age-related muscle loss) produced a modest lean mass gain without a significant improvement in function.
How is trevogrumab different from garetosmab?
Trevogrumab blocks myostatin (GDF8); garetosmab blocks activin A, a related protein that acts through the same receptors. In COURAGE they were tested together in one arm. Our garetosmab article covers that antibody.
Is trevogrumab a peptide?
No. It is a monoclonal antibody of about 150 kilodaltons made in mammalian cell culture. Research peptides are short synthetic amino-acid chains. They are different classes of molecule and cannot be substituted for each other.
What are the most common trevogrumab side effects?
In COURAGE, muscle spasms and injection-site reactions were the events most clearly linked to the antibody; nausea, constipation, diarrhoea, vomiting and reflux track semaglutide. Regeneron described the semaglutide and trevogrumab combinations as generally well tolerated, with most events mild to moderate.
Did anyone die in the trevogrumab trial?
Two participants died, both in the arm that received trevogrumab, garetosmab and semaglutide together. One death was of undetermined cause in a person with multiple cardiovascular risk factors and one was a cardiac arrest in a person with a history of cardiovascular disease. Regeneron has not identified a causal link. No deaths occurred in the arms that received trevogrumab without garetosmab.
Does trevogrumab cause bleeding?
COURAGE did not report a bleeding signal for trevogrumab. Bleeding is watched in this class because ACE-031, an earlier receptor-based ligand trap, was stopped for nosebleeds and gum bleeding, and because garetosmab's FOP label warns of nosebleeds. Trevogrumab binds myostatin only and does not touch the BMP9 and BMP10 proteins implicated in ACE-031's bleeding.
Is trevogrumab safe long term?
Unknown. The obesity data run to 26 weeks for the main part of COURAGE; 52-week results for the lower-dose part were reported on 1 October 2026 and are in press with The Lancet. An earlier sarcopenia trial ran for a similar period. There is no multi-year safety database, no regulatory review and no label.
Information, not advice. This article summarises published research; nothing here is guidance on human or veterinary use. Products are sold under our research use policy.
