# Retatrutide: What the Phase 2 and Phase 3 Trials Have Actually Measured > Retatrutide is an investigational triple-hormone agonist in Phase 3 trials — not yet approved. Phase 2 data: -24.2% body weight at 12 mg over 48 weeks. Dosing, pharmacokinetics, and safety data cited to source. A triple-hormone agonist in Phase 3. Not approved. The dosing schedules, efficacy numbers, and safety signals from the published record — cited, not sold. ## The short version Retatrutide is a drug candidate — not a prescription you can fill, and not approved by any regulator. It is in Phase 3 clinical trials run by Eli Lilly. Before it gets there, a Phase 2 trial gave it to 338 adults with obesity for 48 weeks. At the highest test amount, they lost an average of 24.2% of their body weight. That is a larger number than has been measured with any other drug in this class. The reason it hits harder: most drugs in this family target one or two metabolic receptors at once. Retatrutide targets three — GLP-1 (the receptor that cuts appetite and slows digestion), GIP (the receptor that handles insulin response and fat), and glucagon (the receptor that raises energy burn). Hitting all three at once seems to add up to more weight loss than dual or single agents have produced. The tradeoffs are real. Nausea is common and dose-related. Heart rate climbs measurably. Long-term safety is unknown — those trials are still running. And what people report from community research use — the upsides and the downsides — is on [the effects page](/effects). ## What does retatrutide do Retatrutide (LY3437943) simultaneously activates three class-B G-protein-coupled receptors — GLP-1R, GIPR, and GCGR — with a single 39-amino-acid synthetic peptide engineered on a GIP-based backbone. The GLP-1 arm (glucagon-like peptide-1 receptor, the target of single-agent incretin drugs) suppresses appetite and slows gastric emptying (the rate at which food leaves the stomach). The GIP arm (glucose-dependent insulinotropic polypeptide receptor) augments glucose-dependent insulin secretion and modulates adipose (fat-tissue) metabolism. The glucagon arm activates hepatic (liver) lipid breakdown and increases energy expenditure — the number of calories the body burns at rest [3]. In cryo-EM structural studies, retatrutide is approximately 8.9x more potent at GIPR than native GIP, while operating at 0.4x of GLP-1R and 0.3x of GCGR potency relative to their endogenous hormones [3]. This asymmetric potency profile appears designed to get maximal insulinotropic and adipose benefit from the GIP arm while the GLP-1 and glucagon arms contribute appetite control and energy expenditure without saturating those receptors. The combination drove a mean -24.2% body-weight reduction at 12 mg over 48 weeks in Phase 2 [1] — a magnitude that Phase 3 (the TRIUMPH program) is now working to confirm in larger, longer trials. ## Retatrutide results: what Phase 2 measured The key numbers from the 48-week obesity Phase 2 trial [1]: at 12 mg once weekly, mean body-weight change was -24.2% versus -2.1% for placebo. At 8 mg, -22.8%. At 4 mg, -17.3%. At 1 mg, -8.7%. Every dose beat placebo. The dose-response relationship was consistent and steep. In a separate Phase 2 trial in 281 adults with type 2 diabetes (36 weeks), retatrutide 12 mg reduced HbA1c (glycated hemoglobin — the 3-month average blood sugar marker) by -2.02 percentage points at 24 weeks and body weight by -16.94% at 36 weeks, versus -0.01% HbA1c and -3.00% weight for placebo [2]. Zero severe hypoglycemia events. Zero deaths. In a MASLD substudy (metabolic dysfunction-associated steatotic liver disease — the current term for fatty liver tied to metabolic risk), 12 mg reduced liver fat by -82.4% at 24 weeks, with 86% of participants reaching normal liver fat (below 5% by MRI-PDFF) [5]. Reductions held at 48 weeks. Full [retatrutide results](/results) with the Phase 1 and review data are on the dedicated page. ## Is retatrutide fda approved No. Retatrutide is not FDA-approved and not approved by any regulatory agency as of mid-2026. It is an investigational compound in Phase 3 clinical trials (Eli Lilly's TRIUMPH program). It is not a marketed drug. There is no approved labeled dose, no prescription for it to fill, and no legal supply chain for patient use. The distinction from semaglutide and tirzepatide matters: those are approved and prescribed. Retatrutide is not — it is in the same drug class but at a meaningfully earlier stage. Phase 3 trials are running; regulatory filings, if they happen, are years away. What exists outside clinical trials is gray-market research-labeled material — unregulated, unverified for identity or purity, and outside any clinical oversight. See [Retatrutide effects](/effects) for the safety context. ## Retatrutide vs tirzepatide Both target GIP and GLP-1 receptors. The difference: retatrutide also activates the glucagon receptor (GCGR). That third arm — added energy expenditure, hepatic lipid mobilization — is the proposed mechanism behind retatrutide's larger weight-loss numbers. Phase 2 data for context: tirzepatide's Phase 3 obesity trial produced up to ~22.5% body-weight reduction at 15 mg/72 weeks. Retatrutide's Phase 2 trial showed -24.2% at 12 mg/48 weeks [1][8]. These are not apples-to-apples (different trials, different populations, different durations) — but reviews have characterized retatrutide's Phase 2 numbers as a step-change even within the incretin class [6][8]. A head-to-head Phase 3 active-comparator trial of retatrutide versus tirzepatide is ongoing (NCT06383390) [10]. No results yet. Until those data publish, the comparison is cross-trial extrapolation — worth noting, not worth citing as a verdict. --- A no-vendor reading of the retatrutide trial record — Phase 2 numbers read straight from the source, Phase 3 gaps named as gaps, and nothing here scripted, dispensed, or sold.