Retatrutide (development name LY3437943, Eli Lilly) is an experimental next-generation peptide. As a triple agonist it simultaneously activates three hormone receptors: GLP-1, GIP and glucagon — a unique mechanism that clearly sets it apart from older compounds such as Semaglutide or Tirzepatide.
Mechanism of Action
- GLP-1 agonism: Stimulates insulin release, inhibits glucagon, slows gastric emptying. Promotes satiety and stabilises blood sugar.
- GIP agonism: Enhances the insulinotropic response and supports fat burning. Also involved in bone metabolism.
- Glucagon agonism: Increased energy expenditure via thermogenesis and hepatic lipolysis — a mechanism absent in pure GLP-1 and dual GLP-1/GIP agonists.
The combination of these three pathways produces a synergistic effect: reduced calorie intake and increased energy expenditure simultaneously.
Clinical Studies
The TRIUMPH Phase 2 trial (Eli Lilly, 2023, published in the New England Journal of Medicine) studied Retatrutide over 48 weeks. Result: an average body weight reduction of up to 24.2% in the highest dose group — the highest figure ever documented in a Phase 2 trial for a weight-reduction peptide.
Retatrutide vs. Tirzepatide vs. Semaglutide
| Peptide | Agonism | Avg. reduction (trial) | Status |
|---|---|---|---|
| Semaglutide | GLP-1 | ~15% (STEP-1) | Approved |
| Tirzepatide | GLP-1, GIP | ~22.5% (SURMOUNT-1) | Approved |
| Retatrutide | GLP-1, GIP, Glucagon | ~24% (TRIUMPH) | Phase 2 |
Storage
Retatrutide is supplied as a lyophilized powder. Recommended storage: dry, protected from light at 2–8°C. After reconstitution with sterile water (e.g. BAC Water), keep refrigerated and use within 4 weeks. See our Storage Guide for details.
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