Retatrutide
Retatrutide is a single-molecule 'triple agonist' studied for chronic weight management and type 2 diabetes. In a published Phase 2 obesity trial it produced large dose-dependent weight reductions, and Phase 3 (TRIUMPH) trials are ongoing, with the first positive topline readout reported in late 2025. It remains experimental and is not authorized for clinical use.
Mechanism
In plain terms, retatrutide mimics several natural gut and pancreatic hormones at once to reduce appetite and food intake while affecting how the body handles glucose and energy. Technically, it is a synthetic peptide that simultaneously agonizes the glucose-dependent insulinotropic polypeptide (GIP) receptor, the glucagon-like peptide-1 (GLP-1) receptor, and the glucagon receptor. GLP-1 and GIP activity promote satiety and glucose-dependent insulin secretion, while glucagon-receptor agonism is thought to increase energy expenditure and lipid metabolism, a combination proposed to drive greater weight loss than single- or dual-incretin agents.
Regulatory Status by Region
- United States (FDA)Investigational; not approved. Phase 3 TRIUMPH program ongoing, with a first positive topline readout (TRIUMPH-4) reported in December 2025.
- Australia (TGA)Not entered on the Australian Register of Therapeutic Goods (ARTG); investigational only and not approved for supply.
- European Union (EMA)Not authorized; investigational, no marketing authorization.
- WADANot listed on the WADA Prohibited List. As an investigational incretin-class agent it is not a banned substance; the closely related approved GLP-1 agonists are on WADA's monitoring program rather than prohibited.
Key Studies
- Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial (Jastreboff et al.) (N Engl J Med 2023;389:514-526; DOI 10.1056/NEJMoa2301972; PMID 37366315)
- Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, phase 2 trial (Rosenstock et al.) (Lancet 2023; DOI 10.1016/S0140-6736(23)01053-X; PMID 37385280)
- A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight (TRIUMPH-1, Phase 3) (ClinicalTrials.gov NCT05929066)
Related Clinical Trials
- Effect of LY3437943 Versus Placebo in Participants Who Have Obesity or Are OverweightPhase 2 · Recruiting
- A Study of Retatrutide (LY3437943) in Participants Without Type 2 Diabetes Who Have Obesity or OverweightPhase 3 · Active Not Recruiting
- A Study of Retatrutide (LY3437943) in Participants With Obesity or OverweightPhase 3 · Active Not Recruiting
- A Master Protocol of Multiple Agents in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (SYNERGY-Outcomes)Phase 3 · Recruiting
- A Study to Investigate the Response of Participants With Type 2 Diabetes Mellitus on Once-Weekly Retatrutide to HypoglycemiaPhase 1 · Completed
- A Study to Evaluate the Effect of Retatrutide on Insulin Secretion and Insulin Sensitivity in Adult Participants With Type 2 Diabetes MellitusPhase 1 · Recruiting
- A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight and Chronic Low Back PainPhase 3 · Recruiting
- A Study of Retatrutide (LY3437943) in the Maintenance of Weight Reduction in Individuals With ObesityPhase 3 · Active Not Recruiting