Also known as: REGN1033, REGN-1033, SAR-391786
Lean mass preservation during GLP-1 agonist weight loss therapy
Amount
200-400 mg
Frequency
Subcutaneous injection (dosing interval not publicly specified)
Duration
26-week weight-loss phase followed by 26-week maintenance
Route
SCSchedule
Periodic subcutaneous injection (interval not disclosed)
Timing
Administered in combination with semaglutide 2.4 mg SC weekly in the COURAGE trial. Clinical trial setting only.
Duration
52 weeks (26-week weight-loss + 26-week maintenance)
Repeatable
Single cycle
DXA body composition scan
When: Baseline and 26 weeks
Why: Measure lean mass and fat mass changes
CMP (Comprehensive Metabolic Panel)
When: Baseline
Why: Liver and kidney function baseline
Lipid panel
When: Baseline and 26 weeks
Why: Monitor cardiovascular risk factors
Anti-drug antibodies
When: Periodic
Why: Monitor for immunogenicity
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Trevogrumab (REGN1033) is a fully human immunoglobulin G4 kappa (IgG4-kappa) monoclonal antibody that selectively targets and neutralizes myostatin (also known as growth differentiation factor 8, or GDF-8). Myostatin is the best-characterized negative regulator of skeletal muscle mass, and its blockade leads to increased muscle growth and preservation.
Developed by Regeneron Pharmaceuticals (with Sanofi as a development partner), trevogrumab represents a selective approach to myostatin pathway modulation. Unlike bimagrumab, which blocks activin type II receptors and thereby inhibits multiple TGF-beta superfamily ligands, trevogrumab specifically binds myostatin with no cross-reactivity to the closely related GDF-11.
Trevogrumab works by binding directly to myostatin, preventing it from interacting with activin type II receptors (ActRIIA/ActRIIB) on muscle cells. Under normal conditions, myostatin signals through these receptors to activate the Smad2/3 pathway, which suppresses muscle protein synthesis and promotes muscle catabolism:
GLP-1 receptor agonists like semaglutide and tirzepatide produce significant weight loss, but approximately 30-40% of the weight lost comes from lean mass (primarily muscle). This presents a clinical concern:
The COURAGE trial demonstrated that semaglutide alone caused 34.5% of weight loss to come from lean mass. Adding trevogrumab preserved approximately half of this lean mass while simultaneously increasing fat loss.
The landmark trial for trevogrumab is COURAGE (NCT06299098), a randomized, double-blind, placebo-controlled Phase 2 study in 999 patients with obesity:
| Treatment Arm | Weight Loss | Fat Loss | Lean Mass Preserved |
|---|---|---|---|
| Semaglutide alone | -10.4% (-23.0 lbs) | -15.3 lbs | Reference |
| Semaglutide + trevogrumab 200 mg | -9.9% (-21.6 lbs) | -16.9 lbs | 50.8% |
| Semaglutide + trevogrumab 400 mg | -11.3% (-24.8 lbs) | -18.9 lbs | 51.3% |
| Semaglutide + trevogrumab 400 mg + garetosmab | -13.2% (-30.0 lbs) | -25.4 lbs | 80.9% |
Results were presented at EASD 2025 (26-week analysis).
Regeneron is also evaluating the addition of garetosmab (REGN2477, an anti-activin A antibody) to create a triplet therapy. The combination of trevogrumab + garetosmab addresses both major negative regulators of muscle mass (myostatin and activin A), achieving greater lean mass preservation (80.9%) and enhanced fat loss (27.3% more than semaglutide alone). However, the triplet combination had a notably higher discontinuation rate (28.3%).
| Feature | Trevogrumab | Bimagrumab |
|---|---|---|
| Target | Myostatin (GDF-8) directly | ActRIIA/ActRIIB receptors |
| Specificity | Selective (myostatin only) | Broad (myostatin + activin A + GDF-11) |
| Antibody class | IgG4-kappa | IgG1-lambda |
| Administration | Subcutaneous injection | Intravenous infusion |
| Developer | Regeneron/Sanofi | Novartis/Versanis/Lilly |
| GLP-1 combination trial | COURAGE (with semaglutide) | BELIEVE (with semaglutide) |
Trevogrumab is an investigational drug that has not been approved by any regulatory agency. It is not available for purchase or prescription and can only be accessed through clinical trial enrollment. As a monoclonal antibody (~150 kDa), it cannot be obtained from peptide suppliers or compounding pharmacies. The COURAGE trial is ongoing, and full 52-week results including the weight-maintenance phase have not yet been reported.
Myostatin blockade with a fully human monoclonal antibody induces muscle hypertrophy and reverses muscle atrophy in young and aged mice, published in Skeletal Muscle (Latres E et al., 2015; PMID: 26457176):
Foundational preclinical study characterizing REGN1033 as a specific and potent myostatin antagonist. Chronic treatment of mice with REGN1033 increased muscle fiber size, muscle mass, and force production. REGN1033 prevented muscle atrophy from immobilization, glucocorticoid treatment, and hindlimb unweighting. In aged mice, REGN1033 increased muscle mass, strength, and treadmill exercise performance.
GDF8 and activin A are the key negative regulators of muscle mass in postmenopausal females: a randomized phase I trial, published in Nature Communications (Gonzalez Trotter D et al., 2025; PMID: 40360471):
Two-part, randomized, placebo-controlled Phase 1 trial in 82 healthy postmenopausal women and healthy males. Tested trevogrumab (anti-GDF8) alone, garetosmab (anti-activin A) alone, and combinations. Combination blockade produced dose-dependent increases in MRI-quantitated thigh muscle volume greater than either antibody alone, establishing that GDF8 and activin A are the dominant negative regulators of muscle mass in humans. No anti-drug antibodies detected.
GDF8 and activin A blockade protects against GLP-1-induced muscle loss while enhancing fat loss in obese male mice and non-human primates, published in Nature Communications (Mastaitis JW et al., 2025; PMID: 40360507):
Preclinical study demonstrating that dual blockade of GDF8 and activin A prevents muscle loss associated with GLP-1 receptor agonists and even increases muscle mass in both obese mice and non-human primates. Muscle preservation enhanced fat loss and was metabolically beneficial, providing the preclinical rationale for the COURAGE clinical trial.
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See real-world usage patterns alongside the clinical evidence above. Community-sourced, not clinically verified.
Based on 15+ community reports
View community protocolsACE-031: ActRIIB-Fc myostatin inhibitor for muscle wasting. Covers mechanism, Duchenne dystrophy trials, dosing, side effects, and clinical status.
Apitegromab (SRK-015): anti-promyostatin antibody by Scholar Rock. Phase 3 SAPPHIRE met primary endpoint in SMA. Also studied for lean mass in obesity.
Bimagrumab (BYM338): activin type II receptor antibody for muscle preservation and fat loss. BELIEVE trial showed 22.1% weight loss with semaglutide combo.
Enobosarm (Ostarine/GTx-024): oral SARM for muscle preservation during GLP-1 weight loss. QUALITY Phase 2b positive. PLATEAU trial with tirzepatide planned.
This website is for educational and informational purposes only. The information provided is not intended to diagnose, treat, cure, or prevent any disease. Always consult with a qualified healthcare professional before using any peptide or supplement.
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Comprehensive guide to peptides for muscle growth and preservation โ myostatin inhibitors (follistatin, bimagrumab, trevogrumab, apitegromab), IGF-1 pathway (IGF-1 LR3, MGF), and growth hormone secretagogues (ibutamoren, HGH) with clinical evidence and body recomp strategies.
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