Lilly's retatrutide hits 20.8% weight loss, 1.6% A1C cut in TRIUMPH-2
The Phase 3 diabetes-and-obesity trial met its primary endpoint at 80 weeks, giving Lilly a fifth positive Phase 3 readout ahead of a planned Q1 2027 BLA filing.
Executive Summary
- Eli Lilly's Phase 3 trial of retatrutide in adults with type 2 diabetes and obesity or overweight met its primary weight-loss endpoint at 80 weeks, with the drug also lowering blood sugar control measures across all three tested doses.
- The readout extends a run of positive Phase 3 results for the triple-hormone-receptor agonist, reinforcing a dose-dependent efficacy pattern already shown in earlier retatrutide trials rather than establishing a new finding.
- Lilly is folding this data into a global regulatory package it plans to submit to the FDA in the first quarter of 2027, positioning retatrutide against its own approved incretin franchise and a crowded field of GLP-1 receptor programs from rival sponsors.
- The trial registered two co-primary endpoints, one tied to sleep apnea in a subset of patients and one tied to body-weight change, and only the weight-loss endpoint was confirmed met in the disclosed summary.
The readout
TRIUMPH-2 (NCT05929079) enrolled 1,152 adults with type 2 diabetes and obesity or overweight to test three doses of retatrutide, a GIP, GLP-1, and glucagon triple hormone receptor agonist, against placebo. Lilly said patients on the 4 mg, 9 mg, and 12 mg doses lost an average of 12.7%, 19.1%, and 20.8% of body weight, respectively, at 80 weeks, with A1C reduced by up to an average of 1.6%. Gastrointestinal adverse events, including diarrhea, nausea, and constipation, were more frequent on retatrutide than placebo but were described as consistent with the drug's known profile. "Across five positive Phase 3 studies, retatrutide has shown powerful efficacy," said Kenneth Custer, executive vice president and president of Lilly Cardiometabolic Health. NCT05929079+1A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or OverweightNCT05929079Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1CJul 23, 2026
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
The design
The trial was registered with two co-primary endpoints: percent change in body weight, and change in Apnea-Hypopnea Index for a sleep-apnea subgroup within the study. Lilly's disclosure confirms the body-weight endpoint was met and details the weight and glycemic results, but the announcement centers on the weight-loss and A1C findings rather than the sleep-apnea measure. The trial ran as a randomized, double-blind, four-arm study across the United States, India, Australia, Mexico, Spain, Romania, Argentina, and Brazil, with a primary completion date of May 1, 2026. NCT05929079+1A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or OverweightNCT05929079Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1CJul 23, 2026
Regulatory path
Lilly said it plans to submit a Biologics License Application for retatrutide to the FDA in the first quarter of 2027, drawing on this trial alongside a companion Phase 3 cardiovascular-outcomes study, TRIUMPH-3, which separately showed up to 22.6% weight loss in adults with severe obesity and established cardiovascular disease. In TRIUMPH-3, major adverse cardiovascular events occurred less often than anticipated in both the retatrutide and placebo arms, with a hazard ratio of 0.82 for the composite MACE-5 endpoint. Retatrutide itself is not yet approved in any indication; Lilly's approved incretin portfolio in this space includes tirzepatide, marketed as Zepbound, and orforglipron, marketed as Foundayo, per the same release. Lilly'sLilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1CJul 23, 2026
The competitive field
Retatrutide enters a GLP-1 receptor field that is dense rather than novel: at least 13 direct comparator trials share its target and mechanism class, including Lilly's own tirzepatide and orforglipron programs, Novo Nordisk's CagriSema, Amgen's maridebart cafraglutide, and Roche's enicepatide, all in Phase 3 testing for obesity or type 2 diabetes. Retatrutide is not first-in-class within this landscape, since dozens of GLP-1R-directed peer trials are already registered. Against that backdrop, the bar this data needs to clear is less about proving the mechanism works and more about whether retatrutide's triple-receptor combination separates its weight-loss and glycemic magnitude from Lilly's own dual-agonist tirzepatide on the metrics regulators and prescribers weigh most, durability of effect and tolerability over the same 80-week window.
Track record and stability
The trial's enrollment held flat at its 1,000-patient anticipated target with no material growth or shortfall, a pattern the operational model flags as typical for a Phase 3 program of this size. Its primary completion date moved only once, by two days, from May 3 to May 1, 2026, and its status progressed on schedule from recruiting to active-not-recruiting in November 2024 as enrollment closed. Lilly's sponsor-wide completion rate across 1,810 tracked trials stands at 92.65%, underscoring an execution record that carried this trial to a clean topline readout. NCT05929079A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or OverweightNCT05929079
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.