Retatrutide

Retatrutide (GLP-1/GIP/GCGR Triple Receptor Agonist)

Explore Triple Agonist Research

Evidence & Status

  • Strong Human Evidence
  • Strong

At a Glance

An investigational once-weekly triple agonist targeting GIP, GLP-1, and glucagon receptors. Lilly reported Phase 3 topline average weight-loss results of up to 20.8% at 80 weeks in TRIUMPH-2 and up to 22.6% at 80 weeks in TRIUMPH-3. The complete trial reports have not yet been peer reviewed, and retatrutide is not FDA approved.

Plain English

Researchers study Retatrutide because one molecule activates three hormone pathways involved in metabolic regulation: GIP, GLP-1, and glucagon receptors. Lilly has reported topline results from multiple Phase 3 TRIUMPH trials, including average weight loss of up to 20.8% at 80 weeks in TRIUMPH-2 and up to 22.6% at 80 weeks in TRIUMPH-3. These company-reported results have not yet been published as complete peer-reviewed trial reports. Lilly plans a U.S. filing in Q1 2027, but retatrutide remains investigational and is not FDA approved.

Overview

Retatrutide (LY3437943) is an investigational once-weekly single-molecule agonist of the GIP, GLP-1, and glucagon receptors. Published Phase II trials and sponsor-reported Phase 3 topline results have examined obesity and type 2 diabetes populations. The TRIUMPH-2 and TRIUMPH-3 topline results have not yet been published as complete peer-reviewed trial reports. Retatrutide remains investigational and is not FDA approved.

Research Summary

Retatrutide has published controlled Phase II evidence and sponsor-reported Phase 3 topline results while it remains investigational. In TRIUMPH-2 (NCT05929079), 1,152 adults with type 2 diabetes and obesity or overweight were randomized; Lilly reported average body-weight changes at 80 weeks of -12.7% with 4 mg, -19.1% with 9 mg, and -20.8% with 12 mg, compared with -4.0% with placebo. In TRIUMPH-3 (NCT05882045), 1,949 adults with severe obesity and established cardiovascular disease, with or without type 2 diabetes, were randomized; Lilly reported average body-weight changes at 80 weeks of -21.6% with 9 mg and -22.6% with 12 mg, compared with -3.2% with placebo. These are company-reported topline results and have not yet been published as complete peer-reviewed trial reports; the registry records confirm trial identity and design but do not currently provide posted results. TRIUMPH-3 included exploratory/event analyses of major cardiovascular events, but the reported estimates were imprecise and do not establish cardiovascular-event reduction. Lilly announced plans to submit a U.S. Biologics License Application (BLA) for retatrutide in Q1 2027. A planned filing is not a submitted application or approval. Retatrutide is not FDA approved, and no approved dosing exists. Emerging preclinical research has also examined retatrutide in obesity-associated cancer models. In mouse models of pancreatic cancer, retatrutide delayed tumor onset and progression and produced a 14-fold reduction in tumor volume compared with controls. In a lung cancer model, tumor engraftment was reduced by 50%, tumor onset was delayed, and tumor volume was reduced 17-fold compared with controls. These findings are preclinical; anticancer effectiveness has not been established in humans.

Research Areas

  • Investigational obesity research
  • Investigational type 2 diabetes research
  • Cancer research (animal models)

Safety & Risks

Serious Risks

  • Long-term human safety and clinical outcomes remain incompletely characterized; not approved for use outside clinical trials

Reported Side Effects

  • Nausea
  • Vomiting
  • Diarrhea
  • Decreased appetite
  • Constipation
  • Dysesthesia
  • Injection site reactions
  • Elevated heart rate (dose-dependent)
  • Decreased lean mass at highest doses
United States
Investigational; not FDA approved. Lilly announced plans to submit a U.S. Biologics License Application (BLA) for retatrutide in Q1 2027; a planned filing is not a submitted application or approval
United Kingdom
Current authorization status not established in this record
Australia
Current authorization status not established in this record
Canada
Current authorization status not established in this record

Citations & Sources