# Retatrutide: The Triple-Agonist Clinical Record — Clinic Retatrutide > Retatrutide achieved 28.3% mean weight loss at 80 weeks in Phase 3 TRIUMPH-1 and 82.4% liver fat reduction in Phase 2 MASLD trials. An editorial digest of the peer-reviewed record. An editorial digest of the Jastreboff NEJM Phase 2 trial, TRIUMPH-1 Phase 3 topline, and the full clinical record — every quantitative claim sourced and cited. ## The short version Retatrutide is an investigational drug — not approved anywhere as of 2026, and only accessible through Eli Lilly's authorized clinical trials. It works by activating three hormonal signaling pathways at once: GLP-1 (appetite suppression), GIP (insulin enhancement), and glucagon (increased calorie-burning). No approved drug does all three in a single molecule. The trials have produced large numbers. In the pivotal Phase 2 obesity study published in the New England Journal of Medicine, the highest-dose arm lost an average of 24.2% of body weight over 48 weeks — roughly 58 lbs for a 240-lb person — compared to 2% with placebo. Phase 3 TRIUMPH-1 extended that to 28.3% at 80 weeks. This site summarizes what the published studies have actually measured. It does not sell anything, give medical advice, or help anyone obtain retatrutide outside a clinical trial. The [effects and safety page](/effects) covers what the research community reports and what to watch for. ## What the Retatrutide trials have measured Retatrutide (LY3437943) is a 39-amino acid synthetic peptide engineered to activate three hormone receptors simultaneously — GLP-1R, GIPR, and GCGR — producing complementary effects on appetite, insulin secretion, and energy expenditure. The compound was developed by Eli Lilly and Company and entered clinical trials as an investigational agent for obesity and type 2 diabetes. In the 2023 Phase 2 obesity trial published in the New England Journal of Medicine, participants randomized to 12 mg once weekly achieved 24.2% mean body weight reduction at 48 weeks, compared to 2.1% with placebo [1]. The Phase 3 TRIUMPH-1 trial extended that trajectory: at 80 weeks, the 12 mg arm reached 28.3% mean weight loss — 70.3 lbs — with 45.3% of participants achieving 30% or greater weight loss, a threshold historically associated with bariatric surgery [5]. Beyond weight: the compound's liver data are striking. In a Phase 2a trial published in Nature Medicine, retatrutide 12 mg reduced liver fat by 82.4% at 24 weeks in participants with metabolic dysfunction-associated steatotic liver disease (MASLD), and 86% of the 12 mg group achieved normal liver fat (below 5%) by 48 weeks [3]. Retatrutide is not FDA approved. It is not approved by any regulatory agency as of May 2026. It is available only through authorized Eli Lilly clinical trial enrollment. The Phase 3 TRIUMPH program is ongoing, encompassing obesity, type 2 diabetes, osteoarthritis, and cardiovascular outcomes trials enrolling more than 5,800 participants. This site documents the published research record. ## What is Retatrutide? Retatrutide is an investigational once-weekly subcutaneous triple hormone receptor agonist developed by Eli Lilly and Company (internal designation LY3437943). It is a 39-amino acid synthetic peptide with a molecular weight of approximately 4,731 Da, engineered from a GIP backbone and acylated with a C20 fatty diacid moiety that enables albumin binding for an approximate 6-day plasma half-life [19]. The peptide contains three non-standard residues: Aib at positions 2 and 20, and alpha-methyl-L-leucine at position 13. The Aib2 substitution at the N-terminus confers resistance to DPP-4 cleavage, which normally degrades endogenous GLP-1 in about two minutes. This resistance is what makes once-weekly dosing possible. The compound is sometimes colloquially described as a 'GLP-3' or 'triple GLP.' This is informal shorthand, not a formal pharmacological classification. Its precise designation is a GLP-1/GIP/glucagon receptor co-agonist — three distinct receptor families, one peptide. Phase 2 primary studies were published in the New England Journal of Medicine [1] and the Lancet [2] in 2023. Phase 3 topline results for TRIUMPH-1 (obesity) and TRIUMPH-4 (obesity with osteoarthritis) were announced by Eli Lilly in 2025 [5][8]. ## What Does Retatrutide Do? In Phase 2 clinical trials, retatrutide reduced body weight, liver fat, visceral adipose tissue, HbA1c, triglycerides, systolic blood pressure, and non-HDL cholesterol — all in a dose-dependent fashion. The breadth of metabolic effect reflects the compound's three-pathway activation profile. Body weight: -24.2% mean at 48 weeks for the 12 mg dose in adults with obesity [1]; -16.94% at 36 weeks in adults with type 2 diabetes, outperforming the dulaglutide active control [2]. A network meta-analysis estimated the 12 mg dose at -22.10% body weight versus placebo in indirect comparison with other anti-obesity agents [9]. Liver fat: 82.4% relative reduction at 24 weeks by MRI-PDFF in adults with MASLD (Sanyal 2024, Nature Medicine) [3]. 86% of the 12 mg group reached normal liver fat by 48 weeks. Visceral fat: DXA substudy of the Phase 2 T2D trial showed android visceral fat reduced by up to 31.4% at 36 weeks (Coskun 2025, Lancet Diabetes and Endocrinology) [6]. Cardiovascular markers: non-HDL cholesterol fell by 26.9%, triglycerides by 40.6%, systolic blood pressure by up to 11.8 mmHg, apolipoprotein C-III by 38.0% at 48 weeks in Phase 2 lipid analyses presented at ESC 2024 [11]. HbA1c: -2.02% at 36 weeks in the 12 mg arm of the Phase 2 T2D trial; 82% of participants reached HbA1c at or below 6.5% [2]. ## Who Developed Retatrutide? Eli Lilly and Company developed retatrutide (LY3437943) as part of their GLP-based metabolic drug pipeline. All clinical trials are Lilly-sponsored and registered on ClinicalTrials.gov. Phase 2 studies ran under NCT04881760 (obesity) and NCT04867785 (type 2 diabetes). The Phase 3 TRIUMPH program is registered under NCT05651776 (TRIUMPH-1) and related identifiers. In September 2025, a court ruling vacated FDA's original classification of retatrutide as a small-molecule drug (NDA pathway) and returned the classification to FDA for re-evaluation — Lilly had challenged the classification, arguing retatrutide should be regulated as a biologic (BLA pathway). The regulatory classification remains unresolved as of May 2026, which may affect generic competition timelines and pricing upon approval. ## Research Applications of Retatrutide The primary trial indication is chronic weight management in adults with obesity (BMI 30 or greater, or 27 or greater with at least one comorbidity). Secondary metabolic endpoints under active clinical investigation include: - Type 2 diabetes glycemic control (Phase 2 published; Phase 3 ongoing) - Metabolic dysfunction-associated steatotic liver disease / steatohepatitis (Phase 2a published in Nature Medicine, Phase 3 planned) - Knee osteoarthritis pain reduction via weight loss (TRIUMPH-4 Phase 3 topline announced 2025) - Obstructive sleep apnea (TRIUMPH Phase 3 ongoing) - Cardiovascular outcomes (TRIUMPH-3 ongoing; no CVOT published as of May 2026) The [retatrutide dosage](/dosage) studied across these trials ranged from 1 mg to 12 mg subcutaneous once weekly in Phase 2; Phase 3 tests 4, 9, and 12 mg arms. Read the full [clinical trial data](/references) on the references page. --- A peer-reviewed reading desk — not a clinic, not a vendor, not a source of medical guidance.