What Is Retatrutide?
Retatrutide (LY3437943, informally "GLP-3 RT") is a triple-hormone receptor agonist developed by Eli Lilly. It simultaneously activates GLP-1, GIP, and glucagon receptors — adding a third target beyond tirzepatide's dual mechanism.
The glucagon component is theorized to increase energy expenditure and promote hepatic fat oxidation, potentially addressing metabolic dysfunction more comprehensively.
Mechanism of Action
By engaging all three receptors, retatrutide aims to modulate appetite (GLP-1), improve insulin sensitivity (GIP), and increase metabolic rate through glucagon-mediated thermogenesis. This triple-agonist approach is unprecedented in clinical development.
Key Clinical Data
- Phase 2 trial (2023): Participants receiving the highest dose achieved mean weight loss of 24.2% at 48 weeks — the largest reduction seen in any obesity drug trial at the time (Jastreboff et al., 2023, NEJM)
- Phase 2 MASH data: 90% of participants receiving retatrutide achieved resolution of MASH with no worsening of fibrosis
- Phase 3 trials commenced in late 2023/2024
Cited Sources
- According to Jastreboff, A.M. et al. (2023). "Triple-Hormone-Receptor Agonist Retatrutide for Obesity." NEJM, 389(6), 514-526. [PubMed]
- According to Rosenstock, J. et al. (2023). "Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes." The Lancet, 402(10401), 529-544. [PubMed]