Retatrutide
LY3437943
Retatrutide is an investigational triple GLP-1/GIP/glucagon receptor agonist in Phase 3 TRIUMPH trials, demonstrating significant weight reduction in Phase 2 research.
Overview
Retatrutide (LY3437943) is an investigational synthetic peptide developed by Eli Lilly. It is classified as a triple hormone receptor agonist, meaning it activates three receptors simultaneously: the glucose-dependent insulinotropic polypeptide (GIP) receptor, the glucagon-like peptide-1 (GLP-1) receptor, and the glucagon receptor. This triple-agonist mechanism is a first-in-class approach, adding glucagon receptor activation to the dual GIP/GLP-1 mechanism seen in tirzepatide.
Retatrutide is designed to be administered as a once-weekly subcutaneous injection. The addition of the glucagon receptor target is hypothesized to contribute to additional energy expenditure and metabolic effects beyond what dual agonists achieve. As of early 2026, retatrutide remains an investigational compound and has not been approved for any indication by any regulatory authority.
Research context
Retatrutide has advanced through Phase 2 trials and is currently in Phase 3 development under the TRIUMPH clinical trial program. The Phase 2 trial, published in the New England Journal of Medicine in 2023, evaluated multiple doses in adults with obesity over 48 weeks and reported substantial dose-dependent reductions in body weight at the highest dose level studied.
The TRIUMPH program consists of four Phase 3 trials enrolling over 5,800 participants, evaluating retatrutide for obesity and overweight, obstructive sleep apnea in people with obesity, knee osteoarthritis in people with obesity, and cardiovascular and renal outcomes. The first Phase 3 readout (TRIUMPH-4) was announced in December 2025, with seven additional readouts expected in 2026. Eli Lilly has also initiated additional studies including head-to-head comparisons and maintenance dosing strategies.
Safety and regulatory framing
Phase 3 TRIUMPH program underway; first Phase 3 readout December 2025
Retatrutide is an investigational drug that has not been approved by the FDA or any other regulatory authority for any indication. It is currently available only through enrollment in clinical trials. The safety profile observed in Phase 2 and early Phase 3 data has been generally consistent with other incretin-class therapies, with gastrointestinal symptoms being the most commonly reported adverse events. However, the full safety profile will not be established until the Phase 3 program is complete.
As an investigational compound, retatrutide is not legally available through pharmacies, compounding services, or research chemical suppliers for human use. Regulations vary by country. Readers should consult a licensed healthcare provider for any decisions about investigational therapies or clinical trial participation.
References
- Jastreboff AM, et al. "Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial." NEJM (2023) ↗New England Journal of Medicine
- TRIUMPH-4 Trial ↗ClinicalTrials.gov
- Giblin K, et al. "Retatrutide for the Treatment of Obesity, OSA and Knee OA: Rationale and Design of the TRIUMPH Trials." Diabetes Obes Metab (2026) ↗Diabetes, Obesity and Metabolism
- Eli Lilly TRIUMPH-4 Topline Results Press Release (December 2025) ↗Eli Lilly
- ClinicalTrials.gov Search: Retatrutide ↗ClinicalTrials.gov
Research information only
Peptide Daily is an informational resource only. Peptide research chemicals are not approved for human use by the FDA unless otherwise noted. Nothing on this site constitutes medical advice. Consult a qualified healthcare provider before using any peptide or research chemical.
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