Retatrutide

Triple-receptor agonist peptide

Research overview

Retatrutide, identified in the published literature as LY3437943, is an investigational peptide characterised as an agonist at three separate receptors: the glucose-dependent insulinotropic polypeptide receptor, the glucagon-like peptide-1 receptor, and the glucagon receptor. Coskun and colleagues described its discovery and receptor pharmacology in 2022. Two phase 2 programmes have since been reported: Jastreboff and colleagues examined body-weight endpoints in adults with obesity over 48 weeks, and Rosenstock and colleagues examined glycaemic endpoints in adults with type 2 diabetes against both placebo and an active comparator. Endpoints reported across that work include body weight, HbA1c, fasting glucose, lipid measures and gastrointestinal adverse-event rates. Retatrutide is investigational: no regulator has approved it, and no finished pharmaceutical product containing it exists.

What the literature studies

• ▸Receptor pharmacology at the GIP, GLP-1 and glucagon receptors
• ▸Body-weight endpoints reported in phase 2 obesity trials
• ▸Glycaemic endpoints including HbA1c and fasting glucose in type 2 diabetes trials
• ▸Gastrointestinal adverse-event rates and study discontinuation
• ▸Energy-balance and appetite signalling examined in preclinical models

From the Ironfield research guide (p13)

Retatrutide is an investigational multi-receptor agonist studied in metabolic research for interactions with GIP, GLP-1, and glucagon pathways. Published human studies and newer late-stage trial updates focus on body weight, glycemic markers, cardiometabolic endpoints, and tolerability.

Sources

1. 01Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526. PubMed 37366315
2. 02Rosenstock J, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Lancet. 2023;402(10401):529-544. PubMed 37385280
3. 03Coskun T, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metab. 2022;34(9):1234-1247.e9. PubMed 35985340

Current evidence varies by compound. Many products discussed in this guide remain investigational, are not approved for general clinical use, and should only be handled under qualified research protocols.

No dosing, administration, or treatment instructions are provided.