Retatrutide (LY-3437943)
A synthetic peptide with published binding data at the GIP, GLP-1, and glucagon receptors, used in receptor-pharmacology research.
Overview
Retatrutide is a synthetic peptide designed to bind three class B GPCRs: the glucose-dependent insulinotropic polypeptide (GIP) receptor, the glucagon-like peptide-1 (GLP-1) receptor, and the glucagon receptor. This three-receptor binding profile distinguishes it from earlier compounds designed for one or two of these receptors.
Developed by Eli Lilly and Company under the designation LY-3437943, Retatrutide has been the subject of published discovery-pharmacology work and phase 1 and phase 2 clinical studies. Those studies are cited below for reference only.
Molecular Profile
Receptor Binding Profile
Retatrutide's three-receptor binding profile is what distinguishes it from single- and dual-target peptides in receptor-pharmacology research:
- GLP-1 receptor (GLP-1R):A class B GPCR coupled to Gs. In published cell-based assays, retatrutide's GLP-1R activity is measured by cAMP accumulation and compared with reference ligands such as semaglutide and liraglutide.
- GIP receptor (GIPR):A related class B GPCR. Published in-vitro pharmacology reports retatrutide's relative potency at GIPR alongside its GLP-1R and glucagon receptor values, which is used to characterise its receptor balance.
- Glucagon receptor (GCGR): Binding at the glucagon receptor is the structural feature that distinguishes Retatrutide from dual-target peptides like tirzepatide, and is the main reason it is used in multi-receptor GPCR studies.
Key Published Research
Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-comparator controlled, parallel-group, phase 2 trial
Rosenstock J, et al. The Lancet. 2023; 402(10401):529-544
Phase 2 trial in 281 participants with type 2 diabetes; see source for endpoints.
Triple hormone receptor agonist retatrutide for metabolic disease: a randomised, phase 2 trial
Jastreboff AM, et al. New England Journal of Medicine. 2023; 389(6):514-526
Phase 2 trial in 338 adults; see source for endpoints.
Comparison with Related Compounds
| Compound | Targets | Type |
|---|---|---|
| Semaglutide | GLP-1R | Single-receptor ligand |
| Tirzepatide | GIP-R + GLP-1R | Dual-receptor ligand |
| Retatrutide | GIP-R + GLP-1R + GCGR | Triple-receptor ligand |
Storage and Handling
Lyophilised (unreconstituted):Store at -20°C for long-term stability. Protect from light and moisture.
Reconstituted:Store at 2-8°C. Use within 28 days. Avoid repeated freeze-thaw cycles.
Recommended solvent: Bacteriostatic water or sterile water for laboratory use.
Frequently Asked Questions
What makes Retatrutide different from Tirzepatide?
While Tirzepatide targets two receptors (GIP and GLP-1), Retatrutide adds a third: the glucagon receptor. That additional receptor is why the two are compared in receptor-pharmacology research.
What is the research status of Retatrutide?
Phase 2 clinical trials have been published in The Lancet and the New England Journal of Medicine, and phase 3 trials have been registered.
What purity is required for Retatrutide research?
Research-grade Retatrutide should be ≥98% purity as confirmed by HPLC analysis, with a certificate of analysis available on request.
Disclaimer: This information is compiled from published peer-reviewed literature and is provided for educational and research reference purposes only. It does not constitute medical advice. Retatrutide sold by Enhanced Research Compounds is intended exclusively for in-vitro research and laboratory use. It is not a therapeutic good, is not listed on the ARTG, and is not approved for human or animal consumption.