Retatrutide (RETAPLUS / LY3437943)
Retatrutide acts like three hormones at once that control appetite and fat burning. In studies it showed record weight loss — more than 24% — and greatly reduced liver fat, but it is not yet approved anywhere.
39 amino acids. A triple GLP-1R/GIPR/GlucR agonist with individually optimized affinity. C18 fatty acid. ~4500 Da.
A record among all weight-loss drugs: Phase II (NEJM, n=338) — −24.2% over 48 weeks at a 12 mg dose. In parallel, MASLD: −82.4% liver fat over 24 weeks. Phase III (TRIUMPH): first results published in 2026 — see "New data 2024–2026" below.
Triple activation: GLP-1R (↓appetite, ↑insulin) + GIPR (↑fatty acid β-oxidation, ↑insulin sensitivity) + glucagon R (↑brown adipose tissue thermogenesis, ↑hepatic β-oxidation, ↓lipogenesis). Additive effect of three systems.
Clinical studies used titration: 0.5 mg/week → 4 → 8 → 12 mg/week. Maximum effect at 12 mg. Administration once weekly SC. Course in the study: 48 weeks.
Level A Human clinical trials. There are randomized controlled trials (RCTs), or the compound has been approved by a regulatory agency. The most reliable level. Phase II in NEJM and Lancet. Phase III (TRIUMPH): TRIUMPH-1, TRIUMPH-2, and TRANSCEND-T2D-1 published (2026).
Honest caveat: Not approved by any regulator. Phase 3 data cover up to 80–104 weeks; long-term outcomes are still being studied. Nausea/diarrhea 16–24%. Research only. In studies it was not combined with other GLP-1 agonists.
In 2025–2026, results of the phase 3 program for retatrutide were published. In the TRIUMPH-1 trial (n = 2339, adults with obesity without T2D, 80 weeks; NEJM, 2026), mean body weight reduction was 17.6–25.0% depending on dose vs 3.9% with placebo. In the subgroup that continued 12 mg up to 104 weeks, the reduction reached about 30%. In the TRIUMPH-2 trial (n = 1152, obesity and T2D; Lancet, 2026), weight decreased by 11.9–18.8% vs 5.1%, and HbA1c by 1.4–1.6 percentage points. In the TRANSCEND-T2D-1 trial (n = 537, T2D, 40 weeks; Lancet, 2026), HbA1c decreased by 1.7–1.9 percentage points vs 0.8, and weight by 11.5–15.3%. Substudies and manufacturer press releases (TRIUMPH-3, TRIUMPH-4) describe reductions in the apnea-hypopnea index, knee osteoarthritis pain, and a number of cardiometabolic markers. In a phase 2 substudy (Nat Med, 2024), liver fat content decreased by 81–86% at high doses. A post-hoc analysis of phase 2 showed a reduction in albuminuria. The most common adverse events in these trials were dose-dependent gastrointestinal events. Dysesthesia (up to ~13–21% at the maximum dose), a transient increase in heart rate, and symptomatic hypotension were also described, and the rate of discontinuation due to adverse events at high doses reached 11–18%. Trials of cardiovascular and renal outcomes, MASLD, and CKD are ongoing. The drug is not approved by any regulator (an FDA submission is planned for 2027). This information is provided as a review of published studies and is not a recommendation for use; the reagent described is intended for laboratory research only (RUO).
Research peptides are laboratory reagents (Research Use Only). They are not medicines and are not intended for use in humans or animals.