Retatrutide (LY-3437943)
A novel triple agonist peptide targeting GIP, GLP-1, and glucagon receptors, studied extensively in metabolic and body composition research.
Overview
Retatrutide is a synthetic peptide that simultaneously engages three receptors involved in metabolic regulation: the glucose-dependent insulinotropic polypeptide (GIP) receptor, the glucagon-like peptide-1 (GLP-1) receptor, and the glucagon receptor. This triple agonist mechanism distinguishes it from earlier compounds that targeted only one or two of these pathways.
Developed by Eli Lilly and Company under the designation LY-3437943, Retatrutide entered clinical trials in 2021 and has been the subject of several published phase 1 and phase 2 studies examining its effects on body weight, glucose homeostasis, and metabolic parameters.
Molecular Profile
Mechanism of Action
Retatrutide's triple receptor agonism represents a distinct approach compared to single or dual agonist peptides. Each receptor target contributes different effects:
- GLP-1 receptor agonism: Promotes glucose-dependent insulin secretion, slows gastric emptying, and has been associated with reduced food intake in preclinical models. This pathway is shared with compounds such as semaglutide and liraglutide.
- GIP receptor agonism: The GIP receptor is expressed in pancreatic beta cells, adipose tissue, and the central nervous system. GIP agonism has been studied for its synergistic effects with GLP-1 on insulin secretion and energy balance.
- Glucagon receptor agonism: The addition of glucagon receptor activity distinguishes Retatrutide from dual agonists like tirzepatide. Glucagon signalling has been studied for its role in hepatic glucose output, lipid metabolism, and energy expenditure.
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. Reported dose-dependent effects on HbA1c and body weight over 36 weeks.
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 without diabetes examining dose-dependent effects on body weight. The highest dose group showed a mean body weight change of -24.2% at 48 weeks.
Comparison with Related Compounds
| Compound | Targets | Type |
|---|---|---|
| Semaglutide | GLP-1R | Single agonist |
| Tirzepatide | GIP-R + GLP-1R | Dual agonist |
| Retatrutide | GIP-R + GLP-1R + GCGR | Triple agonist |
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 target: the glucagon receptor. This additional pathway has been studied for its potential effects on energy expenditure and lipid metabolism.
What is the research status of Retatrutide?
Retatrutide has completed phase 2 clinical trials with results published in The Lancet and the New England Journal of Medicine. Phase 3 trials are underway as of 2024.
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.