What Is Retatrutide?
Retatrutide (LY3437943) is an investigational triple-agonist peptide developed by Eli Lilly. It co-activates three receptors involved in energy homeostasis: glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and the glucagon receptor (GCGR). This multi-receptor approach produces additive and synergistic effects on appetite suppression, insulin secretion, and energy expenditure.
Mechanism of Action
| Receptor | Primary Effect | |---|---| | GLP-1R | Appetite suppression, slowed gastric emptying, insulin release | | GIPR | Enhanced insulin secretion, adipose lipid clearance | | GCGR | Elevated energy expenditure, hepatic glucose regulation |
The glucagon component distinguishes retatrutide from dual agonists like tirzepatide — it raises basal metabolic rate, explaining the superior weight loss signal observed in trials.
Phase II Trial Data (2023)
The NEJM-published Phase IIb trial (n=338) showed:
- 17.5% mean body weight reduction at 24 weeks (highest dose arm)
- 24.2% reduction at 48 weeks in extension analysis
- Dose-dependent improvements in HbA1c, triglycerides, and blood pressure
- Primary adverse events: mild-to-moderate GI symptoms consistent with GLP-1 class effects
Research Outlook
Phase III trials (TRIUMPH programme) are ongoing as of 2025. Research applications include obesity, type 2 diabetes, MASLD, and cardiovascular risk reduction.
Related compounds: Semaglutide, Tirzepatide, AOD-9604.