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Retatrutide Reference

Educational, not medical advice reference for Retatrutide: GLP-1, Fat Loss; regulatory status, evidence posture, source review, and schedule not…

Reference summary

Phase 2 (Jastreboff 2023 NEJM, PMID 37366315, n=338 adults with obesity, 48 weeks, NCT04881760): least-squares mean body-weight reductions at 48 weeks were 8.7 percent at 1 mg, 17.1 percent at the combined 4 mg arms, 22.8 percent at the combined 8 mg arms, and 24.2 percent at 12 mg, versus 2.1 percent on placebo. At 48 weeks, weight reduction of 15 percent or more occurred in 60 percent of the 4 mg group, 75 percent of the 8 mg group, 83 percent of the 12 mg group, and 2 percent of placebo. The weight curves had not yet plateaued at the top doses. Phase 3 TRIUMPH-4 (sponsor topline December 2025, NCT05931367, n=445, 68 weeks, obesity or overweight plus knee osteoarthritis): on the efficacy estimand (effect if treatment is taken as randomized), mean body-weight reduction was 26.4 percent at 9 mg and 28.7 percent at 12 mg versus 2.1 percent on placebo; on the treatment-policy estimand (effect including participants who discontinue), reductions were approximately 20 percent at 9 mg and 24 percent at 12 mg. Co-primary WOMAC knee-pain subscale reductions were 4.0 to 4.5 points on active versus about 2.1 on placebo. Secondary cardiometabolic findings at 12 mg included a 14.0 mm Hg systolic blood pressure reduction plus reductions in non-HDL cholesterol, triglycerides, and high-sensitivity C-reactive protein. Phase 3 TRIUMPH-1 (sponsor topline May 2026, NCT05929066, 80 weeks, adults with obesity without diabetes) reported mean weight loss of up to roughly 28 to 30 percent at the 12 mg dose, with a study extension in higher-baseline-BMI participants reaching about 30 percent at 104 weeks. Adverse events were class-typical incretin GI events (nausea, diarrhea, vomiting, constipation, decreased appetite), mostly mild to moderate, concentrated during titration; in Phase 2 GI events were partially mitigated by a lower (2 mg) starting dose. A new dose-related signal not seen in Phase 2 was dysesthesia (altered touch sensation), reported in 8.8 percent at 9 mg and 20.9 percent at 12 mg versus 0.7 percent on placebo in TRIUMPH-4. Dose-dependent heart-rate increases peaked at 24 weeks in Phase 2 and declined thereafter. Hard cardiovascular and kidney outcomes will require TRIUMPH-Outcomes, which has not yet read out; cross-trial efficacy comparisons against semaglutide (STEP-1) and tirzepatide (SURMOUNT-1) rest on different populations, durations, and endpoints.

Regulatory and posture

Categories
GLP-1, Fat Loss
Aliases
LY3437943, GIP / GLP-1 / glucagon triple-receptor agonist, Triple-hormone-receptor agonist (3 receptors), TRIUMPH program drug
Evidence posture
human - Phase 2 (Jastreboff 2023 NEJM) is published, and Phase 3 TRIUMPH-4 (December 2025) and TRIUMPH-1 (May 2026) have reported sponsor topline; the remaining Phase 3 trials, including the cardiovascular and kidney outcomes trial, are still pending, so retatrutide remains investigational. It is not FDA-approved and is not on the FDA bulk substances list for compounding.
Regulatory status
Investigational. Retatrutide (LY3437943) is an Eli Lilly triple-hormone-receptor agonist that activates the glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors. It is in Phase 3 development under the TRIUMPH program (Giblin 2026 Diabetes Obes Metab, PMID 41090431), a four-trial registrational basket plus a dedicated cardiovascular and kidney outcomes trial enrolling more than 5,800 participants combined. The first Phase 3 readout was TRIUMPH-4 (NCT05931367), a 68-week trial in 445 adults with obesity or overweight plus symptomatic knee osteoarthritis without diabetes; sponsor topline was announced on December 11, 2025. TRIUMPH-1 (NCT05929066, 80 weeks, obesity without diabetes) reported sponsor topline in May 2026; TRIUMPH-2 (obesity plus type 2 diabetes), TRIUMPH-3 (obesity plus established cardiovascular disease), and TRIUMPH-Outcomes (NCT06383390, cardiovascular and kidney outcomes) have not yet read out. There is no FDA-approved retatrutide drug label, no approved dose, and no approved indication. Retatrutide is not on the FDA bulk substances list eligible for traditional pharmacy compounding under section 503A, and is not legally available outside the trial program in the United States.
Content review status
investigational verified

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