Retatrutide is a first-in-class investigational triple hormone receptor agonist (GIP, GLP-1, and glucagon) developed by Eli Lilly. In the Phase 2 trial (Jastreboff et al., NEJM 2023, n=338), the 12 mg dose achieved 24.2% mean body weight reduction at 48 weeks, with 100% of participants achieving at least 5% weight loss. Multiple Phase 3 TRIUMPH trials are ongoing, with TRIUMPH-4 (Dec 2025) reporting average loss up to 71.2 lbs with osteoarthritis pain relief. Expected FDA approval is 2027-2028.
Category: Metabolic / Triple Agonist. Evidence rating: B (meaningful human data).
Clinical status: Phase 3 clinical trials (Eli Lilly TRIUMPH program)
Retatrutide simultaneously activates three receptors: GLP-1 (reduces appetite, slows gastric emptying, improves insulin secretion), GIP (enhances insulin sensitivity, glucose control), and glucagon (increases energy expenditure, fat oxidation, thermogenesis). This triple synergy combines reduced…
Research base: 33 registered clinical trials and 71 indexed publications reference Retatrutide.
Safety considerations: GI side effects (dose-related, 13-63% across dose groups): nausea, vomiting, diarrhea, constipation; mostly mild to moderate; GI events partially mitigated with lower starting dose (2 mg vs 4 mg initial dose); Dose-dependent heart rate increases peaking at 24 weeks, declining thereafter.
Reviewed by the PeptideAtlas Editorial Team. Last reviewed: 2026-07-05.
No. Retatrutide is in Phase 3 clinical trials (TRIUMPH program). Not approved for any use. Products sold online are unregulated research chemicals. Expected approval 2027-2028.
Retatrutide targets three receptors (GIP, GLP-1, glucagon) vs tirzepatide's two (GIP, GLP-1). Added glucagon agonism increases thermogenesis. Phase 2: 24.2% at 48 weeks vs tirzepatide 22.5% at 72 weeks. Head-to-head data not available.
Eli Lilly's Phase 3 program: TRIUMPH-1 (obesity), TRIUMPH-2 (T2D), TRIUMPH-3 (CV outcomes), TRIUMPH-4 (obesity+OA). TRIUMPH-4 positive Dec 2025; TRIUMPH-2 positive March 2026.
Based on the Phase 3 timeline, FDA approval is expected in 2027-2028. Currently only available within clinical trials.
No FDA-approved dose exists. Phase 2 tested 1, 4, 8, 12 mg weekly SC. Optimal dose being determined in Phase 3. Self-dosing outside trials is unsafe.