Is trevogrumab FDA-approved?

No. Trevogrumab has not been approved by the FDA for any use. It remains an investigational compound studied in clinical trials.

Does MitoCore sell trevogrumab?

No. This page is a scientific research reference only. MitoCore does not sell, dispense, prescribe, or recommend trevogrumab, and this page contains no dosing or purchasing information.

Is the trevogrumab + garetosmab + semaglutide combination a standard obesity treatment?

No. This three-agent combination is investigational and has only been evaluated within the Phase 2 COURAGE trial. It is not an established or routinely used treatment regimen, and the three-agent group in that trial also had a notably higher rate of stopping treatment due to side effects.

Trevogrumab (REGN1033): Myostatin/GDF8 Monoclonal Antibody Research

Mechanism & Research Overview

Trevogrumab binds directly to myostatin (growth differentiation factor 8, or GDF8), a signaling protein in the TGF-β superfamily that normally acts through activin type II receptors (ActRIIA/ActRIIB) to restrain skeletal-muscle growth.

Mechanism pathway

Relationship-support labels describe the type and directness of the research available, not proof of safety or effectiveness. Indirectly supported, inferred and uncertain relationships are not equivalent to directly supported ones.

CompoundTrevogrumab
Directly supported (Directly supported relationship)
Biological targetMyostatin (GDF8)Extracellular Protein
Supported indirectly (Indirectly supported relationship)
Signal / mechanism stepGDF8/Myostatin activates ActRIIA/ActRIIBMyostatin normally binds activin type II receptors (ActRIIA/ActRIIB) on skeletal muscle.
Supported indirectly (Indirectly supported relationship)
Signal / mechanism stepActRIIA/ActRIIB signaling activates SMAD2/SMAD3Receptor activation triggers downstream SMAD2/3 phosphorylation.
Supported indirectly (Indirectly supported relationship)
Signal / mechanism stepSMAD2/SMAD3 signaling drives negative regulation of skeletal-muscle growthSMAD2/3 activation suppresses muscle-protein synthesis and myogenic transcriptional programs, restraining muscle-mass accrual.
Leads to
PathwayActivin & Myostatin Signaling

Relationship support in this pathway

Directly supported
Supported indirectly

Thin grey links (“Leads to”, “Contributes to”) show structure only and carry no support rating.

Relationship details

Trevogrumab → Myostatin (GDF8) — Directly supportedTrevogrumab binds and neutralizes myostatin (GDF8), preventing it from activating activin type II receptors on skeletal muscle.
GDF8/Myostatin activates ActRIIA/ActRIIB — Supported indirectlySources: SRC-TREVO-002
ActRIIA/ActRIIB signaling activates SMAD2/SMAD3 — Supported indirectlySources: SRC-TREVO-002
SMAD2/SMAD3 signaling drives negative regulation of skeletal-muscle growth — Supported indirectlySources: SRC-TREVO-002, SRC-TREVGARE-001

Open in the Mechanism & Pathway Explorer→

Research Areas Being Studied

Research areas discussed on this page reflect the Metabolic / Weight Management category and the sources cited below.

Findings Reported in Studies

Educational summary only — reported in cited studies, not a claim of proven benefit.

Show findings from 5 human studies

COURAGE Lean-Mass Effects by Baseline Low-Lean-Mass Status (ADA 2026, 1230-OR) (2026):
COURAGE Population-Normed Body-Composition Z-Score Analysis (ADA 2026, 2649-P) (2026):
Phase 1 Study of Garetosmab (REGN2477) Alone and With Trevogrumab (REGN1033) in Healthy Adults (NCT02943239) (2025):
COURAGE: Phase 2 Trial of Semaglutide + Trevogrumab ± Garetosmab in Obesity (NCT06299098) (2024):
Phase 2 Trial of Trevogrumab (REGN1033) in Sarcopenia (NCT01963598) (2015):

Study Tables by Evidence Type

9 study records · 3 with a Study-at-a-Glance summary

Human Studies & Clinical Data 5
Animal / Cell / Preclinical Data 2
Regulatory Documents & Official Trial Registries 1

Human Studies & Clinical Data(5)

Title

Year

Population / Model

Dose / Duration / Finding

Safety Notes

Source

Phase 1 Study of Garetosmab (REGN2477) Alone and With Trevogrumab (REGN1033) in Healthy Adults (NCT02943239)NCT02943239 · DOI 10.1038/s41467-025-59380-3Study-at-a-Glance available

2025

82 healthy postmenopausal women and healthy adult men

Randomized, double-blind, placebo-controlled study using MRI thigh-muscle-volume and DXA body-composition endpoints. Combined blockade of GDF8 (trevogrumab) and Activin A (garetosmab) produced greater muscle growth than either antibody alone, accompanied by fat-mass reductions; effects tracked with antibody exposure and waned as blockade declined. This is healthy-volunteer pharmacology data, not evidence of benefit in FOP or obese populations.

Duration:: Study conducted 2016-12-08 through 2019-04-30 (n=82); published 2025.

Safety note

Generally well tolerated in this healthy-volunteer study. Notable treatment-related events in combination groups included muscle spasms and mouth/aphthous ulcers. No post-treatment anti-drug antibodies were reported.

Nature Communications 2025;16:4376. DOI: 10.1038/s41467-025-59380-3.

View source DOI ClinicalTrials.gov

Key takeaway

This early safety trial in healthy volunteers was not a test of obesity treatment. Blocking two muscle-limiting proteins together increased thigh muscle volume more than blocking either alone at the highest dose, and was generally well tolerated.

READ ORIGINAL STUDY

Study at a Glance

Do two muscle-brake blockers work better than one? An early safety trial in healthy adults

HumanPhase 1RandomizedDouble-blindPlacebo-controlled

Evidence status

Peer-reviewed articleClinical trial registry record

What was being studied?

Whether blocking myostatin (using trevogrumab) and activin A (using garetosmab), two proteins that restrain muscle growth, changes muscle size and body fat, and whether the antibodies are safe.

Who participated?

82 healthy volunteers in New Zealand: 48 in the single-dose part and 34 in the multiple-dose part. They were postmenopausal women aged 45 to 70, and men aged 35 to 60. Only the women received the two-antibody combination.

How was the study done?

Randomized, double-blind, placebo-controlled Phase 1 trial in two parts. In part I women received one dose of trevogrumab alone, garetosmab alone, a combination at several garetosmab doses, or placebo. Part II used repeated doses. Thigh muscle volume was measured by MRI and body composition by DXA scan (a low-dose X-ray body scan).

Key results

At Week 8 after a single dose in women, thigh muscle volume rose 0.88% with placebo and 7.73% with trevogrumab 6 mg/kg plus garetosmab 10 mg/kg, a placebo-adjusted gain of 6.85% (95% CI 3.86 to 9.85). Trevogrumab alone gave 4.61% (nominally significant versus placebo, P=0.0467) and garetosmab alone 2.85% (not significant). Not every combination separated from placebo: with garetosmab 1 mg/kg the gain was 3.51% (not significant), and with 3 mg/kg it was 6.19% (P=0.0056). Total fat mass fell 4.57% in the highest-dose combination, a placebo-adjusted difference of -3.92% (nominal P=0.0173). After repeated dosing, thigh muscle volume rose compared with placebo, then returned to baseline by Week 28.

Measure	Group	Timepoint	Reported value
Thigh muscle volume (MRI), % change from baseline	Placebo (pooled, n=12)	Week 8	0.88%
Thigh muscle volume (MRI), % change from baseline	Garetosmab 10 mg/kg alone (n=6)	Week 8	2.85%difference vs placebo 1.97, not significant
Thigh muscle volume (MRI), % change from baseline	Trevogrumab 6 mg/kg alone (n=6)	Week 8	4.61%difference vs placebo 3.73 (nominal P=0.0467)
Thigh muscle volume (MRI), % change from baseline	Trevogrumab 6 mg/kg + garetosmab 1 mg/kg (n=6)	Week 8	3.51%difference vs placebo 2.63, not significant
Thigh muscle volume (MRI), % change from baseline	Trevogrumab 6 mg/kg + garetosmab 3 mg/kg (n=6)	Week 8	6.19%difference vs placebo 5.31 (nominal P=0.0056)
Thigh muscle volume (MRI), % change from baseline	Trevogrumab 6 mg/kg + garetosmab 10 mg/kg (n=12)	Week 8	7.73%difference vs placebo 6.85 (95% CI 3.86 to 9.85)
Total fat mass (DXA), % change from baseline	Trevogrumab 6 mg/kg + garetosmab 10 mg/kg	Week 8	-4.57%difference vs placebo -3.92 (nominal P=0.0173)

What does this mean?

This was an early safety-focused trial in healthy volunteers, not a test of obesity treatment. Blocking both proteins increased measured thigh muscle size more than blocking either one alone at the higher combination doses, and the increase faded after dosing stopped. This supports further study. It does not show that the combination improves strength, function or health in people with obesity or muscle loss, and the result should not be applied to every dose or combination.

Safety findings

In the single-dose part no serious adverse events, discontinuations or deaths occurred, and events were mild to moderate. Muscle spasms occurred in 7 of 12 (58.3%) of the highest-dose combination group versus 0 on placebo, and mouth ulcers in 3 of 12 (25.0%). One infusion reaction occurred. No participant developed anti-drug antibodies. Muscle spasms and mouth ulcers were also reported more often in the multiple-dose part.

Important limitations

Phase 1 trial with a small number of healthy volunteers; most arms had 6 participants.
The study was not designed to show benefit in people with obesity or muscle loss.
P-values are nominal (not adjusted for multiple comparisons).
The combination was given only to postmenopausal women, not to men.
Results are specific to the doses tested; the lowest combination dose did not separate from placebo at Week 8.
DXA measures were variable in the small multiple-dose group, so MRI muscle volume was the main supported finding there.

Regulatory context

Approved use: Garetosmab (Pasatru) is FDA-approved only for adults with fibrodysplasia ossificans progressiva (FOP).
Investigational use studied here: This study tested muscle and fat effects in healthy volunteers. That is not an approved use of garetosmab, and trevogrumab is investigational.

Sources

Original study: Nature Communications — Journal article
Sources reviewed: Full text reviewed · Trial registry record only.

Other sources for this study (3)

ClinicalTrials.gov NCT02943239 — ClinicalTrials.gov · NCT02943239 · no results section postedContent reviewed for this summary
PubMed 40360471 — PubMed · PMID 40360471Content reviewed for this summary
PubMed Central PMC12075688 — PubMed Central · PMC12075688Content reviewed for this summary

This summary is a plain-language reading aid written by MitoCore. It does not replace the original study, which remains the authoritative source. Research information only, not medical advice.

COURAGE: Phase 2 Trial of Semaglutide + Trevogrumab ± Garetosmab in Obesity (NCT06299098)NCT06299098Study-at-a-Glance available

2024

Adults with obesity (~1,005 enrolled after protocol expansion)

Sponsor-reported Week-26 percent changes: lean mass -6.5% (semaglutide) vs -3.3% (+trevogrumab 200mg), -3.8% (+trevogrumab 400mg), -2.0% (+trevogrumab 400mg+garetosmab); fat mass -15.7% vs -17.3%/-19.1%/-27.1%; body weight -10.6% vs -9.9%/-11.1%/-13.4% respectively. Regeneron's stated interpretation: roughly one-third of semaglutide-associated weight loss in this analysis was lean mass, and trevogrumab-containing arms reduced that lean-mass loss, with the three-agent arm producing the largest lean-mass preservation and fat-mass reduction. This three-agent regimen is investigational, evaluated only within this Phase 2 trial -- not an established or routinely used obesity regimen. The sponsor's term "triplet" refers specifically to this investigational COURAGE arm, not an accepted standard of care. Sponsor-reported Week-52 results (Regeneron release dated 2026-10-01; separate lower-dose portion, trevogrumab 25 mg or 75 mg + semaglutide): lean mass -7.3% (placebo + semaglutide) vs -5.8% (25 mg) and -4.2% (75 mg) at Week 52; at Week 26 in the same portion -6.7%, -4.7% and -3.3%. These lower-dose-portion figures are a different group from the Week-26 higher-dose figures above and must not be combined with them. The sponsor states a Lancet publication is in press; no peer-reviewed publication has been reviewed.

Study/Trial Dosing:: 26-week analysis arms: semaglutide 2.4 mg; semaglutide + trevogrumab 200 mg; semaglutide + trevogrumab 400 mg; semaglutide + trevogrumab 400 mg + garetosmab 10 mg/kg. As reported by the sponsor; not a recommended regimen.

Duration:: Active, not recruiting; study start 2024-03-13; primary completion 2026-06-16 per the latest registry update reviewed, estimated study completion October 2026.

Safety note

Semaglutide + trevogrumab was reported as generally well tolerated. The three-agent arm (adding garetosmab) had a substantially higher discontinuation rate due to tolerability issues/adverse events, and two deaths occurred in that arm; Regeneron stated it had not identified a causal association with treatment (the sponsor's own assessment). Common reported adverse events across groups: muscle spasms, nausea, constipation, fatigue, diarrhea, headache, vomiting, GERD, upper respiratory infection, nasopharyngitis, UTI, influenza, COVID-19. Sponsor-reported 52-week lower-dose portion (release dated 2026-10-01): 77% of trevogrumab participants and 82% of placebo participants had at least one adverse event; events in at least 10% were nausea, constipation, diarrhea and vomiting. These 52-week figures are sponsor-reported; a peer-reviewed publication (stated by the sponsor to be in press with The Lancet) has not been reviewed.

Regeneron Pharmaceuticals. A Study to Learn How Well the Study Medicines Trevogrumab and Garetosmab, Taken in Combination With Semaglutide, Work in Participants Who Have Obesity (COURAGE). ClinicalTrials.gov NCT06299098.

View source ClinicalTrials.gov

Key takeaway

The sponsor reports that adding the experimental drug trevogrumab to semaglutide reduced lean-mass loss in adults with obesity (at 26 and 52 weeks, in different dose groups). The arm that also added garetosmab had more people stop treatment and two deaths.

VIEW TRIAL RECORD VIEW PRIMARY RESULTS SOURCE

Study at a Glance

Does blocking myostatin protect muscle during semaglutide weight loss?

HumanPhase 2RandomizedMasked (per registry)Placebo-controlled

Evidence status

Clinical trial registry recordSponsor report (not peer reviewed)

What was being studied?

Semaglutide, a GLP-1 weight-loss drug, causes loss of both fat and muscle. COURAGE tested whether adding trevogrumab, an antibody that blocks myostatin (a protein that limits muscle growth), reduces the muscle loss. One arm also added garetosmab, an antibody that blocks activin A.

Who participated?

Adults aged 18 to 80 with a BMI of 30 or higher in the weight-loss parts of the trial. The registry lists 1,005 enrolled participants across all parts, including a separate early part in healthy adults with BMI 18 to 32.

How was the study done?

Phase 2, randomized trial run in several parts, with participants, care providers, investigators and outcome assessors masked (per the registry). In the higher-dose portion, people took semaglutide 2.4 mg alone or with trevogrumab 200 mg, trevogrumab 400 mg, or trevogrumab 400 mg plus garetosmab 10 mg/kg for 26 weeks. Semaglutide was then stopped, and trevogrumab or placebo alone was given for another 26 weeks. A separate lower-dose portion tested trevogrumab 25 mg or 75 mg with semaglutide for 52 weeks. Lean and fat mass were measured by DXA scan (a low-dose X-ray body scan); the 52-week release also reports an MRI thigh-muscle substudy. The results below come from sponsor press releases; the ClinicalTrials.gov record has no posted results.

Key results

Week 26, higher-dose portion (Regeneron, 2025): lean mass fell 6.5% with semaglutide alone, versus 3.3% with trevogrumab 200 mg, 3.8% with 400 mg, and 2.0% with the three-drug arm. Fat mass fell 15.7%, 17.3%, 19.1% and 27.1%. Body weight fell 10.6%, 9.9%, 11.1% and 13.4%. Lower-dose portion (Regeneron, 2026): lean mass fell 6.7% at Week 26 and 7.3% at Week 52 with placebo plus semaglutide, versus 3.3% and 4.2% with trevogrumab 75 mg. In an MRI substudy of participants with usable scans, the sponsor reports that trevogrumab 75 mg preserved 72.7% (Week 26) and 68.9% (Week 52) of the thigh muscle volume lost with semaglutide alone. The higher-dose and lower-dose portions are separate groups, and Week 26 and Week 52 figures should not be combined.

Measure	Group	Timepoint	Reported value
Lean mass, % change from baseline (DXA)	Semaglutide alone (n=151)	Week 26	-6.5% (SE 0.5)higher-dose portion
Lean mass, % change from baseline (DXA)	Semaglutide + trevogrumab 200 mg (n=149)	Week 26	-3.3% (SE 0.5)
Lean mass, % change from baseline (DXA)	Semaglutide + trevogrumab 400 mg (n=152)	Week 26	-3.8% (SE 0.5)
Lean mass, % change from baseline (DXA)	Semaglutide + trevogrumab 400 mg + garetosmab 10 mg/kg (n=147)	Week 26	-2.0% (SE 0.6)investigational three-drug arm
Fat mass, % change from baseline (DXA)	Semaglutide alone	Week 26	-15.7% (SE 0.9)
Fat mass, % change from baseline (DXA)	Semaglutide + trevogrumab 400 mg + garetosmab 10 mg/kg	Week 26	-27.1% (SE 1.1)
Body weight, % change from baseline	Semaglutide alone	Week 26	-10.6% (SE 0.5)
Body weight, % change from baseline	Semaglutide + trevogrumab 400 mg + garetosmab 10 mg/kg	Week 26	-13.4% (SE 0.6)
Lean mass, % change from baseline (DXA)	Placebo + semaglutide	Week 26	-6.7% (95% CI -7.9 to -5.5)lower-dose portion
Lean mass, % change from baseline (DXA)	Trevogrumab 75 mg + semaglutide	Week 26	-3.3% (95% CI -4.1 to -2.4)sponsor reports 50.7% lean mass preservation versus placebo + semaglutide
Lean mass, % change from baseline (DXA)	Placebo + semaglutide	Week 52	-7.3% (95% CI -8.8 to -5.8)lower-dose portion
Lean mass, % change from baseline (DXA)	Trevogrumab 75 mg + semaglutide	Week 52	-4.2% (95% CI -5.3 to -3.1)sponsor reports 42.5% lean mass preservation versus placebo + semaglutide
Thigh muscle volume preserved versus placebo + semaglutide (MRI, evaluable participants)	Trevogrumab 25 mg + semaglutide	Week 26	63.6% preservationlower-dose portion; sponsor-calculated
Thigh muscle volume preserved versus placebo + semaglutide (MRI, evaluable participants)	Trevogrumab 25 mg + semaglutide	Week 52	71.8% preservationlower-dose portion; sponsor-calculated
Thigh muscle volume preserved versus placebo + semaglutide (MRI, evaluable participants)	Trevogrumab 75 mg + semaglutide	Week 26	72.7% preservationlower-dose portion; sponsor-calculated
Thigh muscle volume preserved versus placebo + semaglutide (MRI, evaluable participants)	Trevogrumab 75 mg + semaglutide	Week 52	68.9% preservationlower-dose portion; sponsor-calculated

What does this mean?

According to the sponsor, adding trevogrumab reduced how much lean mass was lost during semaglutide weight loss, at the doses and timepoints above. The three-drug arm showed the biggest change in lean mass and fat mass at Week 26 but also the most tolerability problems. These are sponsor-reported results from an ongoing Phase 2 trial, so they are early evidence about body composition, not proof of a health or functional benefit.

Safety findings

Week 26 (sponsor): semaglutide plus trevogrumab was described as generally well tolerated. Adverse events in at least 5% of participants in any group included muscle spasms, nausea, constipation, fatigue, diarrhea, headache, vomiting, reflux, upper respiratory infection, nasopharyngitis, urinary tract infection, influenza and COVID-19. The three-drug arm had a substantially higher rate of discontinuation for tolerability and other adverse events. Two deaths occurred in that arm: one of undetermined cause in a person with several cardiovascular risk factors, and one from cardiac arrest in a person with cardiovascular disease. The sponsor says it has not identified a causal link; that is the sponsor’s own assessment, not an independent finding. Lower-dose portion (sponsor, 52 weeks): 77% of trevogrumab participants and 82% of placebo participants had at least one adverse event, and the most common (10% or more) were nausea, constipation, diarrhea and vomiting.

Important limitations

Results come from sponsor press releases; the ClinicalTrials.gov record has no posted results, and no peer-reviewed paper was reviewed (the sponsor says one is in press).
Week-26 p-values for the primary endpoints were not corrected for multiple comparisons, according to the sponsor.
The higher-dose (200/400 mg) and lower-dose (25/75 mg) portions are separate groups, so their numbers are not interchangeable. The sponsor’s 2025 release also calls the 200 mg arm its “lower-dose” arm, so “lower dose” means different things in the two releases.
MRI results include only participants with usable scans, and the preservation percentages are the sponsor’s own calculations.
The two ADA 2026 abstracts and the 10-Q were not used for figures; their text was not reviewed here.
Lean mass measured by DXA is not the same as muscle strength or physical function.

Regulatory context

Approved use: Garetosmab (Pasatru) is FDA-approved only for adults with fibrodysplasia ossificans progressiva (FOP).
Investigational use studied here: Trevogrumab, and the use of either antibody with semaglutide for obesity or body composition, is investigational.

The three-drug combination is a trial arm. It is not an approved or routine regimen. Semaglutide is the background weight-loss drug; its own approval status is not assessed in this summary.

Sources

Trial record: ClinicalTrials.gov — ClinicalTrials.gov
Primary results source: Regeneron sponsor release: 52-week results (EASD, 1 Oct 2026) (52-week results, lower-dose portion; MRI substudy) — Sponsor releaseSponsor-reported; the sponsor states a Lancet paper is in press. Not a reviewed published article.
Sources reviewed: Trial registry record only · Sponsor-reported results.

Other sources for this study (4)

Regeneron: complete 26-week results (EASD, 17 Sept 2025) — Sponsor releaseContent reviewed for this summary
ADA 2026 abstract 2649-P (population-normed Z-scores) — Conference abstract · DOI 10.2337/db26-2649-P · publisher page blocked automated retrieval; abstract text NOT reviewed for this summaryListed for provenance; content not reviewed
ADA 2026 abstract 1230-OR (low-lean-mass subgroup) — Conference abstract · DOI 10.2337/db26-1230-OR · publisher page blocked automated retrieval; abstract text NOT reviewed for this summaryListed for provenance; content not reviewed
Regeneron Q2 2026 Form 10-Q — Corporate filing · milestone disclosure only; no efficacy or safety figures usedListed for provenance; content not reviewed

This summary is a plain-language reading aid written by MitoCore. It does not replace the original study, which remains the authoritative source. Research information only, not medical advice.

Phase 2 Trial of Trevogrumab (REGN1033) in Sarcopenia (NCT01963598)NCT01963598Study-at-a-Glance available

2015

253 adults age 70+ with objectively measured sarcopenia

Randomized, double-blind, placebo-controlled. Conference-abstract-reported placebo-adjusted total lean-body-mass increases (DXA) of +1.7%, +1.8%, and +2.3% across the three dose groups (~0.7-1.0 kg), with appendicular lean-mass changes of +2.3% to +2.8% vs placebo. Strength/function measures were reported as directionally improved -- not sufficient alone to claim a definitive functional-outcome benefit. Serious-adverse-event frequency was similar between placebo and treated groups in the conference abstract.

Study/Trial Dosing:: Trevogrumab (REGN1033): 100 mg SC every 4 weeks; 300 mg SC every 4 weeks; or 300 mg SC every 2 weeks, vs. placebo. As reported in the trial; not a recommended dose.

Duration:: 12-week treatment period

Safety note

Reported serious-adverse-event rates were similar across placebo and treated groups in the available conference abstract.

Conference Abstract — preliminary, not yet peer-reviewed

Regeneron Pharmaceuticals. REGN1033 (trevogrumab) Phase 2 sarcopenia trial results. Conference abstract, PMC4670752; ClinicalTrials.gov NCT01963598.

View source ClinicalTrials.gov

Key takeaway

A conference abstract reports that in a 12-week Phase 2 trial of 253 older adults with sarcopenia, trevogrumab increased lean body mass by 1.7% to 2.3% more than placebo; this is an abstract, not a peer-reviewed paper.

READ ORIGINAL STUDY

Study at a Glance

HumanPhase 2RandomizedDouble-blindPlacebo-controlled

Evidence status

Conference abstract (not peer reviewed)Clinical trial registry recordAbstract only — full text not reviewed

What was being studied?

Whether trevogrumab (REGN1033), an antibody that blocks myostatin, increases lean body mass in older adults with sarcopenia (age-related muscle loss).

Who participated?

253 adults aged 70 or older with measured sarcopenia (mean age 78, mean lean body mass 43 kg). 95% completed the study.

How was the study done?

12-week, randomized, double-blind, placebo-controlled Phase 2 dose-finding trial sponsored by Regeneron. Participants received placebo every 2 weeks, or trevogrumab 100 mg every 4 weeks, 300 mg every 4 weeks, or 300 mg every 2 weeks, by injection under the skin. The main measure was percent change in total lean body mass by DXA scan from baseline to Week 12. This summary is based on the 2015 conference abstract only.

Key results

Compared with placebo, lean body mass was higher by 1.7% (p=0.008), 1.8% (p=0.004) and 2.3% (p<0.001) in the three trevogrumab groups, corresponding to increases of 0.7, 0.8 and 1.0 kg. Appendicular lean mass (arms and legs) was higher by 2.3% to 2.8% than placebo. Measures of strength and function were described only as directionally greater, with no figures given.

What does this mean?

In this abstract, trevogrumab increased measured lean mass over 12 weeks in older adults with sarcopenia. The abstract does not show that strength or physical function improved by a meaningful amount.

Safety findings

The abstract states trevogrumab was generally safe and well tolerated, with a similar frequency of adverse events across groups. At least one serious adverse event occurred in 7.7% of the placebo group versus 7.4% of the trevogrumab groups, with no discernible pattern. No clinically significant trends were reported in laboratory tests, vital signs, ECGs or echocardiograms.

Important limitations

Conference abstract only; not a peer-reviewed full paper. No full publication was reviewed or cited in the sources used for this summary.
Sponsor-conducted trial; the registry record has no posted results to cross-check the figures.
12 weeks of treatment; long-term effects are not covered.
Strength and function results are described only as directional, with no numbers.

Regulatory context

Investigational use studied here: Trevogrumab for sarcopenia. A Regeneron statement in 2025 says the safety and efficacy of trevogrumab have not been evaluated by any regulatory authority.

Sources

Original study: Conference abstracts (J Cachexia Sarcopenia Muscle, via PMC) — Conference abstract
Sources reviewed: Conference abstract · Trial registry record only.

Other sources for this study (1)

ClinicalTrials.gov NCT01963598 — ClinicalTrials.gov · NCT01963598 · completed; no results section postedContent reviewed for this summary

This summary is a plain-language reading aid written by MitoCore. It does not replace the original study, which remains the authoritative source. Research information only, not medical advice.

COURAGE Lean-Mass Effects by Baseline Low-Lean-Mass Status (ADA 2026, 1230-OR)DOI 10.2337/db26-1230-OR

2026

N=599 with obesity, without type 2 diabetes (COURAGE prespecified subgroup)

Prespecified COURAGE analysis of lean-mass effects stratified by baseline low-lean-mass status, presented at the American Diabetes Association 2026 Scientific Sessions.

Conference Abstract — preliminary, not yet peer-reviewed

American Diabetes Association 2026 Scientific Sessions, abstract 1230-OR. DOI: 10.2337/db26-1230-OR.

DOI

COURAGE Population-Normed Body-Composition Z-Score Analysis (ADA 2026, 2649-P)DOI 10.2337/db26-2649-P

2026

N=599 at baseline/Week 26 (COURAGE)

Population-normed body-composition Z-score analysis of the COURAGE trial, presented at the American Diabetes Association 2026 Scientific Sessions.

Conference Abstract — preliminary, not yet peer-reviewed

American Diabetes Association 2026 Scientific Sessions, abstract 2649-P. DOI: 10.2337/db26-2649-P.

DOI

Phase 1 Study of Garetosmab (REGN2477) Alone and With Trevogrumab (REGN1033) in Healthy Adults (NCT02943239)

2025

NCT02943239 · DOI 10.1038/s41467-025-59380-3

Study-at-a-Glance available

Population / Model: 82 healthy postmenopausal women and healthy adult men

Dose / Duration / Finding

Randomized, double-blind, placebo-controlled study using MRI thigh-muscle-volume and DXA body-composition endpoints. Combined blockade of GDF8 (trevogrumab) and Activin A (garetosmab) produced greater muscle growth than either antibody alone, accompanied by fat-mass reductions; effects tracked with antibody exposure and waned as blockade declined. This is healthy-volunteer pharmacology data, not evidence of benefit in FOP or obese populations.

Show full finding

Duration:: Study conducted 2016-12-08 through 2019-04-30 (n=82); published 2025.

Safety note

Generally well tolerated in this healthy-volunteer study. Notable treatment-related events in combination groups included muscle spasms and mouth/aphthous ulcers. No post-treatment anti-drug antibodies were reported.

Key takeaway

This early safety trial in healthy volunteers was not a test of obesity treatment. Blocking two muscle-limiting proteins together increased thigh muscle volume more than blocking either alone at the highest dose, and was generally well tolerated.

READ ORIGINAL STUDY

Study at a Glance

Do two muscle-brake blockers work better than one? An early safety trial in healthy adults

HumanPhase 1RandomizedDouble-blindPlacebo-controlled

Evidence status

Peer-reviewed articleClinical trial registry record

What was being studied?

Whether blocking myostatin (using trevogrumab) and activin A (using garetosmab), two proteins that restrain muscle growth, changes muscle size and body fat, and whether the antibodies are safe.

Who participated?

82 healthy volunteers in New Zealand: 48 in the single-dose part and 34 in the multiple-dose part. They were postmenopausal women aged 45 to 70, and men aged 35 to 60. Only the women received the two-antibody combination.

How was the study done?

Randomized, double-blind, placebo-controlled Phase 1 trial in two parts. In part I women received one dose of trevogrumab alone, garetosmab alone, a combination at several garetosmab doses, or placebo. Part II used repeated doses. Thigh muscle volume was measured by MRI and body composition by DXA scan (a low-dose X-ray body scan).

Key results

At Week 8 after a single dose in women, thigh muscle volume rose 0.88% with placebo and 7.73% with trevogrumab 6 mg/kg plus garetosmab 10 mg/kg, a placebo-adjusted gain of 6.85% (95% CI 3.86 to 9.85). Trevogrumab alone gave 4.61% (nominally significant versus placebo, P=0.0467) and garetosmab alone 2.85% (not significant). Not every combination separated from placebo: with garetosmab 1 mg/kg the gain was 3.51% (not significant), and with 3 mg/kg it was 6.19% (P=0.0056). Total fat mass fell 4.57% in the highest-dose combination, a placebo-adjusted difference of -3.92% (nominal P=0.0173). After repeated dosing, thigh muscle volume rose compared with placebo, then returned to baseline by Week 28.

Measure	Group	Timepoint	Reported value
Thigh muscle volume (MRI), % change from baseline	Placebo (pooled, n=12)	Week 8	0.88%
Thigh muscle volume (MRI), % change from baseline	Garetosmab 10 mg/kg alone (n=6)	Week 8	2.85%difference vs placebo 1.97, not significant
Thigh muscle volume (MRI), % change from baseline	Trevogrumab 6 mg/kg alone (n=6)	Week 8	4.61%difference vs placebo 3.73 (nominal P=0.0467)
Thigh muscle volume (MRI), % change from baseline	Trevogrumab 6 mg/kg + garetosmab 1 mg/kg (n=6)	Week 8	3.51%difference vs placebo 2.63, not significant
Thigh muscle volume (MRI), % change from baseline	Trevogrumab 6 mg/kg + garetosmab 3 mg/kg (n=6)	Week 8	6.19%difference vs placebo 5.31 (nominal P=0.0056)
Thigh muscle volume (MRI), % change from baseline	Trevogrumab 6 mg/kg + garetosmab 10 mg/kg (n=12)	Week 8	7.73%difference vs placebo 6.85 (95% CI 3.86 to 9.85)
Total fat mass (DXA), % change from baseline	Trevogrumab 6 mg/kg + garetosmab 10 mg/kg	Week 8	-4.57%difference vs placebo -3.92 (nominal P=0.0173)

What does this mean?

This was an early safety-focused trial in healthy volunteers, not a test of obesity treatment. Blocking both proteins increased measured thigh muscle size more than blocking either one alone at the higher combination doses, and the increase faded after dosing stopped. This supports further study. It does not show that the combination improves strength, function or health in people with obesity or muscle loss, and the result should not be applied to every dose or combination.

Safety findings

In the single-dose part no serious adverse events, discontinuations or deaths occurred, and events were mild to moderate. Muscle spasms occurred in 7 of 12 (58.3%) of the highest-dose combination group versus 0 on placebo, and mouth ulcers in 3 of 12 (25.0%). One infusion reaction occurred. No participant developed anti-drug antibodies. Muscle spasms and mouth ulcers were also reported more often in the multiple-dose part.

Important limitations

Phase 1 trial with a small number of healthy volunteers; most arms had 6 participants.
The study was not designed to show benefit in people with obesity or muscle loss.
P-values are nominal (not adjusted for multiple comparisons).
The combination was given only to postmenopausal women, not to men.
Results are specific to the doses tested; the lowest combination dose did not separate from placebo at Week 8.
DXA measures were variable in the small multiple-dose group, so MRI muscle volume was the main supported finding there.

Regulatory context

Approved use: Garetosmab (Pasatru) is FDA-approved only for adults with fibrodysplasia ossificans progressiva (FOP).
Investigational use studied here: This study tested muscle and fat effects in healthy volunteers. That is not an approved use of garetosmab, and trevogrumab is investigational.

Sources

Original study: Nature Communications — Journal article
Sources reviewed: Full text reviewed · Trial registry record only.

Other sources for this study (3)

ClinicalTrials.gov NCT02943239 — ClinicalTrials.gov · NCT02943239 · no results section postedContent reviewed for this summary
PubMed 40360471 — PubMed · PMID 40360471Content reviewed for this summary
PubMed Central PMC12075688 — PubMed Central · PMC12075688Content reviewed for this summary

This summary is a plain-language reading aid written by MitoCore. It does not replace the original study, which remains the authoritative source. Research information only, not medical advice.

Nature Communications 2025;16:4376. DOI: 10.1038/s41467-025-59380-3.

View source DOI ClinicalTrials.gov

COURAGE: Phase 2 Trial of Semaglutide + Trevogrumab ± Garetosmab in Obesity (NCT06299098)

2024

NCT06299098

Study-at-a-Glance available

Population / Model: Adults with obesity (~1,005 enrolled after protocol expansion)

Dose / Duration / Finding

Sponsor-reported Week-26 percent changes: lean mass -6.5% (semaglutide) vs -3.3% (+trevogrumab 200mg), -3.8% (+trevogrumab 400mg), -2.0% (+trevogrumab 400mg+garetosmab); fat mass -15.7% vs -17.3%/-19.1%/-27.1%; body weight -10.6% vs -9.9%/-11.1%/-13.4% respectively. Regeneron's stated interpretation: roughly one-third of semaglutide-associated weight loss in this analysis was lean mass, and trevogrumab-containing arms reduced that lean-mass loss, with the three-agent arm producing the largest lean-mass preservation and fat-mass reduction. This three-agent regimen is investigational, evaluated only within this Phase 2 trial -- not an established or routinely used obesity regimen. The sponsor's term "triplet" refers specifically to this investigational COURAGE arm, not an accepted standard of care. Sponsor-reported Week-52 results (Regeneron release dated 2026-10-01; separate lower-dose portion, trevogrumab 25 mg or 75 mg + semaglutide): lean mass -7.3% (placebo + semaglutide) vs -5.8% (25 mg) and -4.2% (75 mg) at Week 52; at Week 26 in the same portion -6.7%, -4.7% and -3.3%. These lower-dose-portion figures are a different group from the Week-26 higher-dose figures above and must not be combined with them. The sponsor states a Lancet publication is in press; no peer-reviewed publication has been reviewed.

Show full finding

Study/Trial Dosing:: 26-week analysis arms: semaglutide 2.4 mg; semaglutide + trevogrumab 200 mg; semaglutide + trevogrumab 400 mg; semaglutide + trevogrumab 400 mg + garetosmab 10 mg/kg. As reported by the sponsor; not a recommended regimen.

Duration:: Active, not recruiting; study start 2024-03-13; primary completion 2026-06-16 per the latest registry update reviewed, estimated study completion October 2026.

Safety note

Semaglutide + trevogrumab was reported as generally well tolerated. The three-agent arm (adding garetosmab) had a substantially higher discontinuation rate due to tolerability issues/adverse events, and two deaths occurred in that arm; Regeneron stated it had not identified a causal association with treatment (the sponsor's own assessment). Common reported adverse events across groups: muscle spasms, nausea, constipation, fatigue, diarrhea, headache, vomiting, GERD, upper respiratory infection, nasopharyngitis, UTI, influenza, COVID-19. Sponsor-reported 52-week lower-dose portion (release dated 2026-10-01): 77% of trevogrumab participants and 82% of placebo participants had at least one adverse event; events in at least 10% were nausea, constipation, diarrhea and vomiting. These 52-week figures are sponsor-reported; a peer-reviewed publication (stated by the sponsor to be in press with The Lancet) has not been reviewed.

Key takeaway

The sponsor reports that adding the experimental drug trevogrumab to semaglutide reduced lean-mass loss in adults with obesity (at 26 and 52 weeks, in different dose groups). The arm that also added garetosmab had more people stop treatment and two deaths.

VIEW TRIAL RECORD VIEW PRIMARY RESULTS SOURCE

Study at a Glance

Does blocking myostatin protect muscle during semaglutide weight loss?

HumanPhase 2RandomizedMasked (per registry)Placebo-controlled

Evidence status

Clinical trial registry recordSponsor report (not peer reviewed)

What was being studied?

Semaglutide, a GLP-1 weight-loss drug, causes loss of both fat and muscle. COURAGE tested whether adding trevogrumab, an antibody that blocks myostatin (a protein that limits muscle growth), reduces the muscle loss. One arm also added garetosmab, an antibody that blocks activin A.

Who participated?

Adults aged 18 to 80 with a BMI of 30 or higher in the weight-loss parts of the trial. The registry lists 1,005 enrolled participants across all parts, including a separate early part in healthy adults with BMI 18 to 32.

How was the study done?

Phase 2, randomized trial run in several parts, with participants, care providers, investigators and outcome assessors masked (per the registry). In the higher-dose portion, people took semaglutide 2.4 mg alone or with trevogrumab 200 mg, trevogrumab 400 mg, or trevogrumab 400 mg plus garetosmab 10 mg/kg for 26 weeks. Semaglutide was then stopped, and trevogrumab or placebo alone was given for another 26 weeks. A separate lower-dose portion tested trevogrumab 25 mg or 75 mg with semaglutide for 52 weeks. Lean and fat mass were measured by DXA scan (a low-dose X-ray body scan); the 52-week release also reports an MRI thigh-muscle substudy. The results below come from sponsor press releases; the ClinicalTrials.gov record has no posted results.

Key results

Week 26, higher-dose portion (Regeneron, 2025): lean mass fell 6.5% with semaglutide alone, versus 3.3% with trevogrumab 200 mg, 3.8% with 400 mg, and 2.0% with the three-drug arm. Fat mass fell 15.7%, 17.3%, 19.1% and 27.1%. Body weight fell 10.6%, 9.9%, 11.1% and 13.4%. Lower-dose portion (Regeneron, 2026): lean mass fell 6.7% at Week 26 and 7.3% at Week 52 with placebo plus semaglutide, versus 3.3% and 4.2% with trevogrumab 75 mg. In an MRI substudy of participants with usable scans, the sponsor reports that trevogrumab 75 mg preserved 72.7% (Week 26) and 68.9% (Week 52) of the thigh muscle volume lost with semaglutide alone. The higher-dose and lower-dose portions are separate groups, and Week 26 and Week 52 figures should not be combined.

Measure	Group	Timepoint	Reported value
Lean mass, % change from baseline (DXA)	Semaglutide alone (n=151)	Week 26	-6.5% (SE 0.5)higher-dose portion
Lean mass, % change from baseline (DXA)	Semaglutide + trevogrumab 200 mg (n=149)	Week 26	-3.3% (SE 0.5)
Lean mass, % change from baseline (DXA)	Semaglutide + trevogrumab 400 mg (n=152)	Week 26	-3.8% (SE 0.5)
Lean mass, % change from baseline (DXA)	Semaglutide + trevogrumab 400 mg + garetosmab 10 mg/kg (n=147)	Week 26	-2.0% (SE 0.6)investigational three-drug arm
Fat mass, % change from baseline (DXA)	Semaglutide alone	Week 26	-15.7% (SE 0.9)
Fat mass, % change from baseline (DXA)	Semaglutide + trevogrumab 400 mg + garetosmab 10 mg/kg	Week 26	-27.1% (SE 1.1)
Body weight, % change from baseline	Semaglutide alone	Week 26	-10.6% (SE 0.5)
Body weight, % change from baseline	Semaglutide + trevogrumab 400 mg + garetosmab 10 mg/kg	Week 26	-13.4% (SE 0.6)
Lean mass, % change from baseline (DXA)	Placebo + semaglutide	Week 26	-6.7% (95% CI -7.9 to -5.5)lower-dose portion
Lean mass, % change from baseline (DXA)	Trevogrumab 75 mg + semaglutide	Week 26	-3.3% (95% CI -4.1 to -2.4)sponsor reports 50.7% lean mass preservation versus placebo + semaglutide
Lean mass, % change from baseline (DXA)	Placebo + semaglutide	Week 52	-7.3% (95% CI -8.8 to -5.8)lower-dose portion
Lean mass, % change from baseline (DXA)	Trevogrumab 75 mg + semaglutide	Week 52	-4.2% (95% CI -5.3 to -3.1)sponsor reports 42.5% lean mass preservation versus placebo + semaglutide
Thigh muscle volume preserved versus placebo + semaglutide (MRI, evaluable participants)	Trevogrumab 25 mg + semaglutide	Week 26	63.6% preservationlower-dose portion; sponsor-calculated
Thigh muscle volume preserved versus placebo + semaglutide (MRI, evaluable participants)	Trevogrumab 25 mg + semaglutide	Week 52	71.8% preservationlower-dose portion; sponsor-calculated
Thigh muscle volume preserved versus placebo + semaglutide (MRI, evaluable participants)	Trevogrumab 75 mg + semaglutide	Week 26	72.7% preservationlower-dose portion; sponsor-calculated
Thigh muscle volume preserved versus placebo + semaglutide (MRI, evaluable participants)	Trevogrumab 75 mg + semaglutide	Week 52	68.9% preservationlower-dose portion; sponsor-calculated

What does this mean?

According to the sponsor, adding trevogrumab reduced how much lean mass was lost during semaglutide weight loss, at the doses and timepoints above. The three-drug arm showed the biggest change in lean mass and fat mass at Week 26 but also the most tolerability problems. These are sponsor-reported results from an ongoing Phase 2 trial, so they are early evidence about body composition, not proof of a health or functional benefit.

Safety findings

Week 26 (sponsor): semaglutide plus trevogrumab was described as generally well tolerated. Adverse events in at least 5% of participants in any group included muscle spasms, nausea, constipation, fatigue, diarrhea, headache, vomiting, reflux, upper respiratory infection, nasopharyngitis, urinary tract infection, influenza and COVID-19. The three-drug arm had a substantially higher rate of discontinuation for tolerability and other adverse events. Two deaths occurred in that arm: one of undetermined cause in a person with several cardiovascular risk factors, and one from cardiac arrest in a person with cardiovascular disease. The sponsor says it has not identified a causal link; that is the sponsor’s own assessment, not an independent finding. Lower-dose portion (sponsor, 52 weeks): 77% of trevogrumab participants and 82% of placebo participants had at least one adverse event, and the most common (10% or more) were nausea, constipation, diarrhea and vomiting.

Important limitations

Results come from sponsor press releases; the ClinicalTrials.gov record has no posted results, and no peer-reviewed paper was reviewed (the sponsor says one is in press).
Week-26 p-values for the primary endpoints were not corrected for multiple comparisons, according to the sponsor.
The higher-dose (200/400 mg) and lower-dose (25/75 mg) portions are separate groups, so their numbers are not interchangeable. The sponsor’s 2025 release also calls the 200 mg arm its “lower-dose” arm, so “lower dose” means different things in the two releases.
MRI results include only participants with usable scans, and the preservation percentages are the sponsor’s own calculations.
The two ADA 2026 abstracts and the 10-Q were not used for figures; their text was not reviewed here.
Lean mass measured by DXA is not the same as muscle strength or physical function.

Regulatory context

Approved use: Garetosmab (Pasatru) is FDA-approved only for adults with fibrodysplasia ossificans progressiva (FOP).
Investigational use studied here: Trevogrumab, and the use of either antibody with semaglutide for obesity or body composition, is investigational.

The three-drug combination is a trial arm. It is not an approved or routine regimen. Semaglutide is the background weight-loss drug; its own approval status is not assessed in this summary.

Sources

Trial record: ClinicalTrials.gov — ClinicalTrials.gov
Primary results source: Regeneron sponsor release: 52-week results (EASD, 1 Oct 2026) (52-week results, lower-dose portion; MRI substudy) — Sponsor releaseSponsor-reported; the sponsor states a Lancet paper is in press. Not a reviewed published article.
Sources reviewed: Trial registry record only · Sponsor-reported results.

Other sources for this study (4)

Regeneron: complete 26-week results (EASD, 17 Sept 2025) — Sponsor releaseContent reviewed for this summary
ADA 2026 abstract 2649-P (population-normed Z-scores) — Conference abstract · DOI 10.2337/db26-2649-P · publisher page blocked automated retrieval; abstract text NOT reviewed for this summaryListed for provenance; content not reviewed
ADA 2026 abstract 1230-OR (low-lean-mass subgroup) — Conference abstract · DOI 10.2337/db26-1230-OR · publisher page blocked automated retrieval; abstract text NOT reviewed for this summaryListed for provenance; content not reviewed
Regeneron Q2 2026 Form 10-Q — Corporate filing · milestone disclosure only; no efficacy or safety figures usedListed for provenance; content not reviewed

This summary is a plain-language reading aid written by MitoCore. It does not replace the original study, which remains the authoritative source. Research information only, not medical advice.

Regeneron Pharmaceuticals. A Study to Learn How Well the Study Medicines Trevogrumab and Garetosmab, Taken in Combination With Semaglutide, Work in Participants Who Have Obesity (COURAGE). ClinicalTrials.gov NCT06299098.

View source ClinicalTrials.gov

Phase 2 Trial of Trevogrumab (REGN1033) in Sarcopenia (NCT01963598)

2015

NCT01963598

Study-at-a-Glance available

Population / Model: 253 adults age 70+ with objectively measured sarcopenia

Dose / Duration / Finding

Randomized, double-blind, placebo-controlled. Conference-abstract-reported placebo-adjusted total lean-body-mass increases (DXA) of +1.7%, +1.8%, and +2.3% across the three dose groups (~0.7-1.0 kg), with appendicular lean-mass changes of +2.3% to +2.8% vs placebo. Strength/function measures were reported as directionally improved -- not sufficient alone to claim a definitive functional-outcome benefit. Serious-adverse-event frequency was similar between placebo and treated groups in the conference abstract.

Show full finding

Study/Trial Dosing:: Trevogrumab (REGN1033): 100 mg SC every 4 weeks; 300 mg SC every 4 weeks; or 300 mg SC every 2 weeks, vs. placebo. As reported in the trial; not a recommended dose.

Duration:: 12-week treatment period

Safety note

Reported serious-adverse-event rates were similar across placebo and treated groups in the available conference abstract.

Key takeaway

A conference abstract reports that in a 12-week Phase 2 trial of 253 older adults with sarcopenia, trevogrumab increased lean body mass by 1.7% to 2.3% more than placebo; this is an abstract, not a peer-reviewed paper.

READ ORIGINAL STUDY

Study at a Glance

HumanPhase 2RandomizedDouble-blindPlacebo-controlled

Evidence status

Conference abstract (not peer reviewed)Clinical trial registry recordAbstract only — full text not reviewed

What was being studied?

Whether trevogrumab (REGN1033), an antibody that blocks myostatin, increases lean body mass in older adults with sarcopenia (age-related muscle loss).

Who participated?

253 adults aged 70 or older with measured sarcopenia (mean age 78, mean lean body mass 43 kg). 95% completed the study.

How was the study done?

12-week, randomized, double-blind, placebo-controlled Phase 2 dose-finding trial sponsored by Regeneron. Participants received placebo every 2 weeks, or trevogrumab 100 mg every 4 weeks, 300 mg every 4 weeks, or 300 mg every 2 weeks, by injection under the skin. The main measure was percent change in total lean body mass by DXA scan from baseline to Week 12. This summary is based on the 2015 conference abstract only.

Key results

Compared with placebo, lean body mass was higher by 1.7% (p=0.008), 1.8% (p=0.004) and 2.3% (p<0.001) in the three trevogrumab groups, corresponding to increases of 0.7, 0.8 and 1.0 kg. Appendicular lean mass (arms and legs) was higher by 2.3% to 2.8% than placebo. Measures of strength and function were described only as directionally greater, with no figures given.

What does this mean?

In this abstract, trevogrumab increased measured lean mass over 12 weeks in older adults with sarcopenia. The abstract does not show that strength or physical function improved by a meaningful amount.

Safety findings

The abstract states trevogrumab was generally safe and well tolerated, with a similar frequency of adverse events across groups. At least one serious adverse event occurred in 7.7% of the placebo group versus 7.4% of the trevogrumab groups, with no discernible pattern. No clinically significant trends were reported in laboratory tests, vital signs, ECGs or echocardiograms.

Important limitations

Conference abstract only; not a peer-reviewed full paper. No full publication was reviewed or cited in the sources used for this summary.
Sponsor-conducted trial; the registry record has no posted results to cross-check the figures.
12 weeks of treatment; long-term effects are not covered.
Strength and function results are described only as directional, with no numbers.

Regulatory context

Investigational use studied here: Trevogrumab for sarcopenia. A Regeneron statement in 2025 says the safety and efficacy of trevogrumab have not been evaluated by any regulatory authority.

Sources

Original study: Conference abstracts (J Cachexia Sarcopenia Muscle, via PMC) — Conference abstract
Sources reviewed: Conference abstract · Trial registry record only.

Other sources for this study (1)

ClinicalTrials.gov NCT01963598 — ClinicalTrials.gov · NCT01963598 · completed; no results section postedContent reviewed for this summary

This summary is a plain-language reading aid written by MitoCore. It does not replace the original study, which remains the authoritative source. Research information only, not medical advice.

Conference Abstract — preliminary, not yet peer-reviewed

Regeneron Pharmaceuticals. REGN1033 (trevogrumab) Phase 2 sarcopenia trial results. Conference abstract, PMC4670752; ClinicalTrials.gov NCT01963598.

View source ClinicalTrials.gov

COURAGE Lean-Mass Effects by Baseline Low-Lean-Mass Status (ADA 2026, 1230-OR)

2026

DOI 10.2337/db26-1230-OR

Population / Model: N=599 with obesity, without type 2 diabetes (COURAGE prespecified subgroup)

Dose / Duration / Finding: Prespecified COURAGE analysis of lean-mass effects stratified by baseline low-lean-mass status, presented at the American Diabetes Association 2026 Scientific Sessions.

Conference Abstract — preliminary, not yet peer-reviewed

American Diabetes Association 2026 Scientific Sessions, abstract 1230-OR. DOI: 10.2337/db26-1230-OR.

DOI

COURAGE Population-Normed Body-Composition Z-Score Analysis (ADA 2026, 2649-P)

2026

DOI 10.2337/db26-2649-P

Population / Model: N=599 at baseline/Week 26 (COURAGE)

Dose / Duration / Finding: Population-normed body-composition Z-score analysis of the COURAGE trial, presented at the American Diabetes Association 2026 Scientific Sessions.

Conference Abstract — preliminary, not yet peer-reviewed

American Diabetes Association 2026 Scientific Sessions, abstract 2649-P. DOI: 10.2337/db26-2649-P.

DOI

Animal / Cell / Preclinical Data(2)

Title	Year	Population / Model	Dose / Duration / Finding	Safety Notes	Source
Preclinical GLP-1 Combination Bridge: Myostatin/Activin A Blockade and Obesity-Model Body CompositionDOI 10.1038/s41467-025-59485-9	2025		Preclinical work bridging GDF8/Activin A blockade with GLP-1-driven weight loss in an obesity model, providing mechanistic rationale later tested in the COURAGE trial. Preclinical evidence only -- not human obesity outcome data.		Nature Communications 2025. DOI: 10.1038/s41467-025-59485-9. DOI
Preclinical Characterization of REGN1033 (Trevogrumab): Selective Myostatin Antagonism in MicePMID 26457176	2015		REGN1033 showed selective, potent myostatin antagonism in mice, increasing muscle fiber size, muscle mass, and force, including protection/recovery in several experimental muscle-atrophy models. Preclinical mechanistic evidence -- not proof of clinical outcomes in humans.		View source PubMed

Preclinical GLP-1 Combination Bridge: Myostatin/Activin A Blockade and Obesity-Model Body Composition

2025

DOI 10.1038/s41467-025-59485-9

Population / Model

Dose / Duration / Finding: Preclinical work bridging GDF8/Activin A blockade with GLP-1-driven weight loss in an obesity model, providing mechanistic rationale later tested in the COURAGE trial. Preclinical evidence only -- not human obesity outcome data.

Nature Communications 2025. DOI: 10.1038/s41467-025-59485-9.

DOI

Preclinical Characterization of REGN1033 (Trevogrumab): Selective Myostatin Antagonism in Mice

2015

PMID 26457176

Population / Model

Dose / Duration / Finding: REGN1033 showed selective, potent myostatin antagonism in mice, increasing muscle fiber size, muscle mass, and force, including protection/recovery in several experimental muscle-atrophy models. Preclinical mechanistic evidence -- not proof of clinical outcomes in humans.
Show full findingShow less

View source PubMed

Regulatory Documents & Official Trial Registries(1)

Title	Year	Population / Model	Dose / Duration / Finding	Safety Notes	Source
Regeneron Q2 2026 Form 10-Q: COURAGE 52-Week Readout Milestone Disclosure	2026		In its Form 10-Q for the quarter ended June 30, 2026, Regeneron disclosed its plan to present 52-week COURAGE trial results, including findings from an MRI substudy in a subset of participants, at the European Association for the Study of Diabetes (EASD) 2026 meeting. Update (2026-10-06): Regeneron has since issued a sponsor release dated 2026-10-01 reporting those 52-week results; see the COURAGE trial record.		SEC / Corporate Filing — not a medical regulatory source View source

Regeneron Q2 2026 Form 10-Q: COURAGE 52-Week Readout Milestone Disclosure

2026

Population / Model

Dose / Duration / Finding: In its Form 10-Q for the quarter ended June 30, 2026, Regeneron disclosed its plan to present 52-week COURAGE trial results, including findings from an MRI substudy in a subset of participants, at the European Association for the Study of Diabetes (EASD) 2026 meeting. Update (2026-10-06): Regeneron has since issued a sponsor release dated 2026-10-01 reporting those 52-week results; see the COURAGE trial record.
Show full findingShow less

SEC / Corporate Filing — not a medical regulatory source

View source

Review Articles / Secondary Sources(1)

Title	Year	Population / Model	Dose / Duration / Finding	Safety Notes	Source
Regeneron: Complete 26-Week COURAGE Trial Results (Sponsor Press Release)	2025		Sponsor summary of the same 26-week COURAGE results captured in the COURAGE trial record (NCT06299098); the primary public-facing sponsor announcement of those results, dated 2025-09-17.		Sponsor Press Release — not peer-reviewed View source

Regeneron: Complete 26-Week COURAGE Trial Results (Sponsor Press Release)

2025

Population / Model

Dose / Duration / Finding: Sponsor summary of the same 26-week COURAGE results captured in the COURAGE trial record (NCT06299098); the primary public-facing sponsor announcement of those results, dated 2025-09-17.

Sponsor Press Release — not peer-reviewed

View source

Anecdotal Reported Patterns — Not Medical Advice

Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.

Lab Markers to Discuss With a Clinician

Educational topics only — not self-monitoring instructions.

FAQ

No. Trevogrumab is a monoclonal antibody -- a large, lab-made immune protein -- not a peptide. It works completely differently from the peptide therapies discussed elsewhere on this site.

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Disclaimer

This page is a scientific research reference. It does not offer trevogrumab for sale, and does not recommend, prescribe, or provide dosing or usage instructions for it. Trevogrumab has not been evaluated or approved by the FDA for any use.

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Content status: Content pending review. Last updated 2026-09-27.

Trevogrumab

Key facts

Evidence Snapshot

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Regulatory Context

In Plain English

What is it?

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What does the evidence look like?

Biggest things to know

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Research status

Research Takeaway

Quick Summary

Mechanism & Research Overview

Mechanism pathway

Evidence Claims

Safety & Evidence Limitations

Research Areas Being Studied

Findings Reported in Studies

Study Tables by Evidence Type

Human Studies & Clinical Data(5)

What was being studied?

Who participated?

How was the study done?

Key results

What does this mean?

Safety findings

Important limitations

Regulatory context

Sources

What was being studied?

Who participated?

How was the study done?

Key results

What does this mean?

Safety findings

Important limitations

Regulatory context

Sources

What was being studied?

Who participated?

How was the study done?

Key results

What does this mean?

Safety findings

Important limitations

Regulatory context

Sources

Phase 1 Study of Garetosmab (REGN2477) Alone and With Trevogrumab (REGN1033) in Healthy Adults (NCT02943239)

What was being studied?

Who participated?

How was the study done?

Key results

What does this mean?

Safety findings

Important limitations

Regulatory context

Sources

COURAGE: Phase 2 Trial of Semaglutide + Trevogrumab ± Garetosmab in Obesity (NCT06299098)

What was being studied?

Who participated?

How was the study done?

Key results

What does this mean?

Safety findings

Important limitations

Regulatory context

Sources

Phase 2 Trial of Trevogrumab (REGN1033) in Sarcopenia (NCT01963598)

What was being studied?

Who participated?

How was the study done?

Key results

What does this mean?

Safety findings

Important limitations

Regulatory context

Sources

COURAGE Lean-Mass Effects by Baseline Low-Lean-Mass Status (ADA 2026, 1230-OR)