Retatrutide (LY3437943) is a next-generation, once-weekly injectable peptide developed by Eli Lilly as a triple agonist of GLP-1, GIP, and Glucagon receptors. Phase 2 clinical trials demonstrated weight loss of up to 24% of body weight over 48 weeks — surpassing all currently available anti-obesity pharmacotherapies. This research-grade vial contains 10mg of Retatrutide as lyophilized powder.
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About this compound
Retatrutide (LY3437943) is an acylated synthetic peptide engineered by Eli Lilly as the world's first GIP/GLP-1/glucagon triple agonist. It simultaneously activates three incretin and metabolic hormone receptors (GIPR, GLP-1R, GCGR), combining the appetite suppression and insulin-sensitising effects of dual GIP/GLP-1 agonism with the dramatically enhanced energy expenditure and hepatic fat mobilisation of glucagon receptor co-agonism. Its Phase II data — showing 24.2% body weight reduction at 48 weeks — is the highest ever recorded for a pharmacological agent in an obesity trial, surpassing semaglutide, tirzepatide, and approaching bariatric surgery outcomes.
Research Data
Research Snapshot — Retatrutide
Key Mechanisms & Pathways
- GLP-1R Agonism / CNSSuppresses NPY and AgRP in hypothalamic ARC/PVN — reducing appetite drive. Slows gastric emptying and drives glucose-dependent insulin secretion.
- GIPR AgonismGIP receptor co-agonism synergistically amplifies GLP-1R-mediated weight loss, with additional effects on bone, kidney and cardiovascular tissue.
- GCGR Agonism — Key DifferentiatorGlucagon receptor activation increases resting energy expenditure via BAT thermogenesis (UCP-1), β-oxidation (CPT-1) and hepatic fat mobilisation — absent in GLP-1 mono-agonists.
- Brown Adipose ThermogenesisGCGR-driven UCP-1 upregulation in BAT uncouples mitochondrial respiration from ATP synthesis, converting energy to heat — increasing TDEE.
- Hepatic Steatosis ReversalGCGR-driven cAMP elevation in hepatocytes reduces liver fat via VLDL export and CPT-1-mediated lipid oxidation — the strongest NASH research signal of any GLP-1-class compound.
- Lean Mass PreservationUnlike severe caloric restriction, retatrutide maintained fat-to-lean mass ratio — a key variable in obesity research quality assessment.
Preclinical & Clinical Research Summary
| Research Area | Key Finding | Source |
|---|---|---|
| Phase II Weight Loss | −24.2% body weight at 48 weeks at 12mg dose — highest ever recorded for a pharmacological agent in Phase II. | Jastreboff AM et al., 2023 — N Engl J Med |
| Dose-Response | 4mg: −17.5%; 8mg: −22.8%; 12mg: −24.2%. Responder rate (≥5% loss) at 12mg: >96%. | Jastreboff AM et al., 2023 — N Engl J Med |
| Type 2 Diabetes | HbA1c reduced by 2.02% vs. 0.27% placebo; weight loss −16.94% at 24 weeks in T2D patients. | Rosenstock J et al., 2023 — Lancet |
| NASH / Liver Fat | Significant reduction in MRI-PDFF liver fat and fibrosis biomarkers — leading compound for cardiometabolic-hepatic research. | Cusi K et al., 2023 — EASL Congress |
References
- Jastreboff AM et al. "Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial." N Engl J Med, 2023;389(6):514–526.
- Rosenstock J et al. "Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes." Lancet, 2023;402(10401):529–544.
- Coskun T et al. "LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss." Cell Metab, 2022;34(9):1234–1247.
- Jastreboff AM et al. "Retatrutide — phase 3 program design and rationale." Obesity, 2024.
Specifications
- Sequence
- GIP/GLP-1/Glucagon triple receptor agonist
- Molecular Weight
- ~4500 Da
- Amino Acids
- Acylated peptide
- Half-Life
- ~6 days (SC)
- CAS Number
- 2381089-83-2
- Vial Size
- 10mg
- Purity
- ≥99% (HPLC)
- Form
- Lyophilized powder
- Reconstitution
- Bacteriostatic water (0.9% benzyl alcohol)
- Storage
- Sealed: 2–8 °C · Reconstituted: 2–8 °C, use within 28 days
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