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Investigational triple agonist (GLP‑1/GIP/glucagon). Phase 2 data show large, dose‑dependent weight loss and improvements in metabolic markers. Potential benefits include potent appetite reduction plus higher energy expenditure via glucagon signaling. Long‑term safety and outcomes are still under evaluation.
Description
Retatrutide (LY3437943) is an investigational, acylated peptide that acts as a triple agonist at the glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon (GCGR) receptors. This multi-receptor profile is designed to combine incretin-driven appetite and glycemic effects (GLP-1, GIP) with glucagon-mediated increases in energy expenditure and lipid mobilization. In a phase 2 obesity study, retatrutide produced substantial weight reduction over 48 weeks with dose-dependent effects.
Chemical Structure / Identifiers
| Property | Detail |
| Class/Targets | Triple agonist: GLP-1R, GIPR, and GCGR |
| Molecular Formula (PubChem) | C221H342N46O68 |
| Approx. Molecular Weight (PubChem) | ≈ 4731 g/mol |
| CAS Number | 2381089-83-2 |
| PubChem CID | 171390338 (retatrutide free base); 171934787 (sodium salt) |
| Synonyms | LY3437943; retatrutide [INN] |
| Sequence/Notes | Peptide sequence available in public databases/patents; long-chain acylation used for half-life extension |
Primary Research Focus
• Obesity and weight management: phase 2 trial reported mean weight reduction up to ~24% at 48 weeks at the highest dose in adults with obesity without diabetes.
• Glycemic and metabolic effects: improvements in glycemic markers in early studies; ongoing evaluation versus active comparators.
• Cardiometabolic biomarkers and liver fat: reports of reductions in triglycerides, apoC-III, and liver fat content in development program updates.
• Mechanistic rationale: GLP-1/GIP promote satiety and insulinotropic effects; GCGR engagement may increase energy expenditure and fat oxidation.
Safety / Limitations
• Adverse events consistent with incretin/glucagon agonism: gastrointestinal events (nausea, vomiting, diarrhea) were common and dose-related in trials; dose titration was used to improve tolerability.
• Transient heart rate increases and other class effects are being monitored; full long-term cardiovascular and hepatic safety remain under study.
• Drug is investigational; phase 3 trials are ongoing. Safety and efficacy are not established for clinical use outside trials.
Key Publications / References
NEJM (2023): Triple–Hormone–Receptor Agonist Retatrutide for Obesity. https://www.nejm.org/doi/full/10.1056/NEJMoa2301972
PubMed record for the NEJM phase 2 trial (NCT04881760). https://pubmed.ncbi.nlm.nih.gov/37366315/
PubChem Compound Summary: Retatrutide (CID 171390338) and sodium salt (CID 171934787). https://pubchem.ncbi.nlm.nih.gov/compound/171390338 https://pubchem.ncbi.nlm.nih.gov/compound/171934787
ClinicalTrials.gov: Maintenance and comparative studies in obesity (examples NCT06662383, NCT06859268). https://clinicaltrials.gov/study/NCT06662383 https://clinicaltrials.gov/study/NCT06859268
FDA UNII / substance registry entry (precisionFDA GSRS). https://precision.fda.gov/ginas/app/ui/substances/NOP2Y096GV
Overview and identifiers (background): https://en.wikipedia.org/wiki/Retatrutide
News summary of biomarker effects in development program. https://www.reuters.com/business/healthcare-pharmaceuticals/health-rounds-next-generation-lilly-weight-loss-drug-shows-added-heart-liver-benefits-2024-09-06/
Disclaimer: For research background only. Retatrutide is investigational and not approved for general clinical use.
| Quantity | 10MG, 30MG, 60MG |
|---|
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