# Retatrutide Research: Phase 1, 2 and 3 Trial Evidence — Mechanism, Efficacy and Kidney Data > Retatrutide research covers Phase 1b pharmacokinetics, Phase 2 obesity and diabetes trials, MASLD liver-fat data, and Phase 3 kidney outcomes — a cited digest of the published record. From first-in-human pharmacokinetics to the 48-week Phase 2 efficacy trials and the ongoing Phase 3 program — everything cited to its primary source. ## The evidence in plain terms Retatrutide is an investigational compound currently in Phase 3 clinical trials. The research record is unusually detailed for a drug that has not been approved: two Phase 2 trials have been published in top-tier journals, structural biology has mapped exactly how the molecule docks to its three receptor targets, and substudies have measured liver fat, kidney function, and body composition in subsets of trial participants. This page walks through the Retatrutide research chronologically — from first-in-human Phase 1b studies through the 48-week Phase 2 trials in obesity and type 2 diabetes, through to the data emerging from the ongoing Phase 3 TRIUMPH program. The key numbers are up front in each section, and the source for every figure is noted. Jargon is defined on first use. ## Phase 1b: pharmacokinetics and first efficacy signal The first-in-human data for retatrutide (LY3437943) were published in *The Lancet* in 2022 [4]. The Phase 1b trial enrolled 72 adults with type 2 diabetes and studied multiple ascending doses over 12 weeks. Two findings set the direction for everything that followed. First, the half-life (the time for blood concentration to fall by half, which determines how often a drug needs to be given) was approximately 6 days — long enough to support once-weekly subcutaneous (under the skin) dosing [4]. Most peptide drugs have much shorter half-lives; retatrutide's extended half-life comes from a C20 fatty-diacid modification that binds the molecule to albumin (a protein in the blood), slowing its clearance. Second, placebo-adjusted weight loss at the highest dose group reached -8.96 kg over 12 weeks [4]. For a first-in-human study, this was a notable efficacy signal. Treatment-emergent adverse events occurred in 63% of participants, mostly GI in nature, and the safety profile was judged acceptable at all doses studied. Retatrutide half life: approximately 6 days, supporting once-weekly subcutaneous administration [4]. ## Phase 2 in obesity: the 24.2% weight loss trial The Phase 2 obesity trial, published in the *New England Journal of Medicine* in 2023, is the most cited retatrutide study [1]. It enrolled 338 adults with obesity (body mass index — BMI, a ratio of weight to height squared — of 30 or above, or 27–30 with a weight-related health condition) and randomized them to weekly subcutaneous doses of 1, 4, 8, or 12 mg, or placebo, for 48 weeks. At 48 weeks, the 12 mg group had a mean body-weight change of -24.2% versus -2.1% with placebo [1]. At 4 mg, the mean change was -8.7%; at 8 mg, -17.3%. Weight loss was ongoing and had not plateaued by the end of the 48-week trial, suggesting the efficacy ceiling had not been reached [1, 6]. Gastrointestinal adverse events — nausea, vomiting, diarrhea, constipation — were dose-related, occurring in approximately 73% of participants at the highest dose and driving an 18% discontinuation rate at that dose. Dose-dependent increases in resting heart rate, peaking around week 24, were also documented [1]. For the full presentation of [retatrutide results](/results), see the dedicated results page. ## Phase 2 in type 2 diabetes: glycemic and weight data The Phase 2 diabetes trial, published in *The Lancet* in 2023, enrolled 281 adults with type 2 diabetes and studied doses from 0.5 to 12 mg over 36 weeks [2]. At 24 weeks, the 12 mg group had reduced HbA1c — glycated hemoglobin (HbA1c), the standard 3-month average glucose marker — by 2.02 percentage points versus -0.01% with placebo [2]. At 36 weeks, body weight in the 12 mg group had fallen by 16.94% versus -3.00% with placebo [2]. No severe hypoglycemia and no deaths were reported. GI adverse events affected 35% of participants. Dose escalation — starting at 0.5 mg and stepping up over weeks — was used to reduce GI adverse-event severity [2]. A 2024 *Clinical Diabetes* profile described retatrutide as the first-in-class GIP/GLP-1/glucagon triple agonist for obesity, with a mechanism and magnitude of effect that distinguish it from prior incretin agents [10]. ## Phase 2 substudy in MASLD: liver-fat reduction MASLD — metabolic dysfunction-associated steatotic liver disease, the current clinical term for fatty liver linked to metabolic risk factors (formerly called NAFLD, non-alcoholic fatty liver disease) — is closely linked to obesity and type 2 diabetes. A Phase 2a substudy published in *Nature Medicine* in 2024 enrolled 98 participants with obesity or overweight and confirmed liver fat (at least 10%, measured by MRI-PDFF — magnetic resonance imaging proton density fat fraction, a non-invasive liver-fat measurement) and no diabetes [5]. At 24 weeks, the 12 mg group had a relative liver-fat reduction of -82.4% versus +0.3% with placebo. By week 48, this had deepened to -86.0% at 12 mg. In the 12 mg group, 86% of participants reached normal liver fat (under 5%) by week 24 [5]. This is the first Phase 2 dataset for retatrutide in liver disease specifically. Phase 3 liver-disease data are pending. ## Retatrutide vs tirzepatide: what the comparative data show Retatrutide vs tirzepatide is one of the most searched questions in this space, but a direct head-to-head trial has not yet reported results. A 2025 review summarizing retatrutide's mechanism and Phase 1/2 data characterizes the up-to ~24% weight loss at 12 mg/48 weeks as a step-change relative to prior incretin therapies [6]. An active Phase 3 trial (part of the TRIUMPH program) will compare retatrutide directly with tirzepatide, a dual GIP/GLP-1 agonist. Until that trial reports, direct comparison figures are not available from controlled studies. What can be said from the published record: Phase 2 retatrutide data show a maximum mean weight loss of 24.2% at 48 weeks [1]. The key mechanistic difference is the addition of glucagon receptor agonism, which is absent in tirzepatide and drives additional energy expenditure and hepatic lipid mobilization [3, 6]. Whether this translates to clinically superior long-term outcomes is an open question that Phase 3 will answer. ## What does retatrutide do: mechanism in brief What does retatrutide do at the molecular level? It activates three class-B G-protein-coupled receptors (GPCRs — a family of cell-surface receptors that relay signals into cells via a protein called G-protein) simultaneously: GLP-1R, GIPR, and GCGR. Cryo-EM structural studies resolved its binding at resolutions of 2.68–3.26 Å (angstroms — a unit of atomic-scale distance) [3]. At the GIPR, retatrutide is approximately 8.9 times more potent than native GIP; at GCGR and GLP-1R it is 0.3 and 0.4 times as potent as the respective endogenous hormones [3]. The net effect — appetite suppression plus energy expenditure increase plus improved insulin secretion — is why Phase 2 weight-loss figures exceed those of single or dual agonists [6]. For a full walkthrough, see [how does retatrutide work](/how-it-works). ## Is retatrutide fda approved Is retatrutide fda approved? No. As of mid-2026, retatrutide has not been approved by the FDA, the EMA, or any other regulatory agency. It is an investigational new drug (IND) in Phase 3 clinical trials under Eli Lilly's TRIUMPH program. Approval, if granted, would follow the completion and regulatory review of Phase 3 data — a process that typically takes several years from Phase 3 initiation. The 2025 systematic review of 53 obesity Phase 2/3 trials confirmed retatrutide among 14 agents in active Phase 3 development [9]. ## The ongoing Phase 3 program The TRIUMPH program comprises multiple Phase 3 trials in obesity, type 2 diabetes, cardiovascular outcomes, and kidney outcomes. NCT06383390 is a dedicated cardiovascular and kidney outcomes trial [7]. NCT05929066 and NCT05931367 address obesity and T2D efficacy. The TRANSCEND-CKD trial — published as its design paper in *Nephrology Dialysis Transplantation* in 2025 — specifically evaluates retatrutide in people with chronic kidney disease (CKD — a progressive decline in kidney filtering function) [12]. None of these Phase 3 trials have reported results as of mid-2026. The [Retatrutide references](/references) page lists the registered trial identifiers and available publications. --- A blueprint-level reading of the published retatrutide trial record — Phase 2 figures logged to source, the kidney and cardiac questions marked open, and no clinic, prescription, or product behind the drafting sheet.