# Retatrutide (LY3437943): The Triple-Agonist Trial Record, Filed and Footnoted > Retatrutide is an investigational GIP/GLP-1/glucagon triple agonist showing up to -24.2% body-weight change in Phase 2 trials. A broadsheet record of what the studies actually measured. An independent broadsheet of the published retatrutide trial literature — every figure study-attributed, every gap marked, nothing dispensed or sold. ## The short version — plain English first Retatrutide (sometimes called LY3437943 by its development code) is an investigational drug — meaning it is still in clinical trials and not approved by any regulator as of 2026. It works by activating three hormone receptors at once: GLP-1 (which curbs appetite and helps the body manage blood sugar), GIP (which also supports insulin release and affects fat tissue), and glucagon (which increases the amount of energy the body burns at rest). Hitting three targets instead of one is why early trial results were striking. In the largest Phase 2 trial, participants taking the highest study dose lost an average of 24.2% of their body weight over 48 weeks — a result researchers and reviewers described as a meaningful step up from earlier single- or dual-receptor drugs. The most common side effects were nausea, constipation, and other gut discomfort, which were dose-related and mostly mild-to-moderate. Heart rate increased modestly in some participants. Retatrutide does not treat or cure anything yet — it is investigational. The [Retatrutide effects](/effects) and [Retatrutide research](/research) pages document what the trials actually measured in detail. ## What does retatrutide do Retatrutide is a 39-amino-acid synthetic peptide developed by Eli Lilly. It is a simultaneous agonist — activator — at three class-B G-protein-coupled receptors: the GLP-1 receptor (GLP-1R), the GIP receptor (GIPR), and the glucagon receptor (GCGR). The GLP-1 and GIP arms suppress appetite and improve glucose-dependent insulin secretion (the release of insulin in proportion to how much blood sugar is present, a mechanism that reduces low-blood-sugar risk). The glucagon arm increases resting energy expenditure (how many calories the body burns at rest) and promotes hepatic lipid mobilization (breakdown of fat stored in the liver). No prior approved anti-obesity compound activates all three in a single molecule [6]. Structural cryo-EM data show retatrutide binding simultaneously to all three receptors; it is approximately 8.9-fold more potent at GIPR than native GIP, while its activity at GCGR and GLP-1R is roughly 0.3x and 0.4x the potency of the native hormones respectively [3]. The combined effect — appetite suppression, improved insulin sensitivity, and elevated caloric burn — is the mechanistic basis for the Phase 2 weight-loss findings. ## Phase 2 trial record: the headline numbers The pivotal Phase 2 obesity trial enrolled 338 adults with obesity or overweight with at least one comorbidity. At 48 weeks, the 12 mg once-weekly arm produced a mean body-weight change of -24.2% versus -2.1% in the placebo arm [1]. In the parallel Phase 2 trial in type 2 diabetes, 12 mg reduced HbA1c (glycated hemoglobin — a three-month blood-sugar average) by -2.02% at 24 weeks and body weight by -16.94% at 36 weeks versus -0.01% HbA1c and -3.00% body weight in the placebo arm [2]. A substudy in metabolic dysfunction-associated steatotic liver disease (MASLD — formerly called NAFLD, a condition of excess fat stored in the liver) found 12 mg reduced liver fat by -82.4% at 24 weeks, with 86% of participants reaching normal liver fat content (<5%) as measured by MRI-PDFF [5]. The [retatrutide results](/results) page reports these numbers in full, stratified by dose arm. A 2026 cardiovascular-kidney-metabolic review reported 63% of participants achieving ≥20% total body-weight loss, 8.79 mmHg systolic blood-pressure reduction, and significant attenuation of urine albumin-to-creatinine ratio [11]. ## Body composition: fat versus lean mass The 24% weight figure includes both fat mass and lean mass — and the split matters. A 2025 body-composition substudy in the type 2 diabetes Phase 2 trial (DXA scans, the imaging method for body-composition measurement) confirmed dose-dependent reductions in total fat mass alongside the expected proportional change in lean mass [7]. The fat-to-lean loss ratio was more favorable than bariatric surgery benchmarks in that dataset, but absolute lean-mass loss remains clinically meaningful during rapid weight reduction, particularly for older individuals and those with low muscle reserve. A 2024 rodent study showed that higher dietary protein defended lean mass without compromising fat loss or metabolic improvements during pharmacologic weight reduction [8]. The [retatrutide results](/results) page covers the body-composition data in detail. Community discussion — clearly labeled anecdotal — similarly flags lean mass as the top tracking concern among those following the trial literature; [Retatrutide effects](/effects) documents those reports. ## Is retatrutide fda approved No. Retatrutide is investigational. It is not approved by the FDA, the EMA, or any regulatory agency as of mid-2026. Eli Lilly's TRIUMPH Phase 3 program — a multi-trial series in obesity, type 2 diabetes, cardiovascular outcomes, chronic kidney disease (the TRANSCEND-CKD trial), and an active-comparator study versus tirzepatide — is ongoing, and results have not been reported. A dedicated cardiovascular-outcomes trial is also running. [Retatrutide availability](/faq) and the regulatory record are addressed in the FAQ. Until Phase 3 data are published and a regulatory submission is reviewed, retatrutide has no approved indication anywhere in the world. ## Retatrutide availability and gray-market note Because retatrutide is not approved, it is not commercially available as a prescription product. Research-labeled material sold through unregulated channels has no verified identity, purity, or sterility. The FDA issued over 50 warning letters to vendors of such material in 2025 citing Federal FD&C Act violations. This site does not link to vendors, does not sell retatrutide, and does not provide sourcing guidance. [Retatrutide references](/references) lists the published trial literature this broadsheet reports from. --- A broadsheet record of the retatrutide trial literature — every figure dated to its study, every gap filed in plain ink, no clinic behind the masthead.