Retatrutide (LY-343794)
Retatrutide (LY-343794) is an investigational triple agonist targeting GIP, GLP-1, and glucagon receptors simultaneously, designed to add the thermogenic and hepatic fat-mobilizing effects of glucagon receptor activation to the weight loss and glycemic benefits of dual GIP/GLP-1 agonism. Phase 2 data (NEJM, 2023) showed mean body weight reductions of approximately 24% at the highest dose over 48 weeks in adults with obesity — the largest weight loss magnitude reported for any pharmacological agent in a randomized trial at the time. The glucagon receptor component requires careful balancing as glucagon raises blood glucose, but at the doses studied the GLP-1/GIP-mediated insulin secretion appears to offset this risk. Phase 3 trials under the TRIUMPH program are ongoing; no regulatory approval has been granted and retatrutide is not available outside clinical trials.
Evidence last reviewed: 04 Apr 2026
Not a routine supplement — not recommended for self-directed use.
Information here is educational only, not a recommendation to use. See our Safety page.
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Evidence is from research or clinical settings — does not imply safety outside supervised contexts.
Phase 2 trials indicate retatrutide can lead to substantial weight loss, with reductions of up to 24% over 48 weeks. However, ongoing Phase 3 trials are necessary to confirm its efficacy and safety in larger populations.
Body weight reductionAdults with obesity (without diabetes) in a randomized controlled phase 2 trial · Randomized, double-blind, placebo-controlled phase 2 trialHigh
Retatrutide produced substantial mean body-weight reductions over 48 weeks (up to ~24% at highest dose), with larger losses at higher doses; GI adverse effects were common & dose-related.
Phase 3 registrational program design (TRIUMPH)Adults with obesity ± OSA, knee osteoarthritis, or cardiovascular disease (>5800 participants across 4 trials) · Phase 3 registrational program design/rationale publicationLow
The TRIUMPH phase 3 program (4 trials, >5800 participants) evaluates once-weekly subcutaneous retatrutide vs. placebo for weight management & obesity-related complications (OSA, OA, CVD). No primary efficacy results published as of early 2026; design & rationale published in 2025.
Clinical Weight Loss Protocol
Investigational/clinical agents with strong RCT evidence in obesity-related indications (not supplements).
Investigational/clinical agents with strong RCT evidence in obesity-related indications (not supplements).
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