Retatrutide TRIUMPH Trial Tracker

TRIUMPH-4: The First Phase 3 Readout

TRIUMPH-4 is the first trial in the TRIUMPH program to report Phase 3 results. The trial enrolled participants with obesity and knee osteoarthritis — a population where weight loss directly addresses the mechanical and inflammatory drivers of joint disease.

The headline numbers: participants receiving retatrutide achieved a mean 28.7% body weight loss, the highest figure reported in any retatrutide trial to date. This exceeded the 24.2% seen in Phase 2 at 48 weeks, likely due to the longer treatment duration and the specific population studied.

Beyond weight loss, TRIUMPH-4 demonstrated clinically meaningful improvements in knee OA pain as measured by validated pain scoring instruments. The combination of substantial weight reduction and direct pain relief makes this a significant dataset for Lilly’s regulatory strategy. For a detailed analysis of the knee OA findings, see our retatrutide and knee osteoarthritis deep dive.

TRIUMPH-1: The Pivotal Obesity Trial

TRIUMPH-1 is the primary pivotal trial for the obesity indication — the trial that will form the core of Lilly’s NDA submission. It enrolls adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related comorbidity, excluding type 2 diabetes.

This is a randomized, double-blind, placebo-controlled trial with a treatment duration designed to demonstrate sustained weight loss over a clinically meaningful period. Results are expected in 2026 and will provide the definitive efficacy and safety data needed for FDA review. The primary endpoints are percent change in body weight and the proportion of participants achieving ≥5% weight loss.

TRIUMPH-2: Obesity with Type 2 Diabetes

TRIUMPH-2 evaluates retatrutide in people with obesity and type 2 diabetes — a population where the triple agonist mechanism is particularly relevant. The GIP receptor component enhances glucose-dependent insulin secretion, the GLP-1 component provides appetite suppression and additional glycemic control, and the glucagon component increases hepatic glucose output regulation and energy expenditure.

Phase 2 data in the T2D subgroup showed a 1.9% reduction in HbA1c alongside substantial weight loss, indicating dual benefit in metabolic parameters. TRIUMPH-2 results are expected in 2026 and will be critical for a potential diabetes-plus-obesity label.

TRIUMPH-3: Cardiovascular Outcomes

TRIUMPH-3 is a cardiovascular outcomes trial (CVOT) enrolling participants with obesity and established cardiovascular disease. This trial is designed to demonstrate that retatrutide reduces major adverse cardiovascular events (MACE) — a requirement that has become standard for the obesity drug class following semaglutide’s SELECT trial results.

CVOTs are inherently longer than weight-loss trials due to the need to accumulate sufficient cardiovascular events. Results are not expected until 2027 at the earliest. While TRIUMPH-3 data may not be required for initial FDA approval of the obesity indication, a positive CVOT would significantly broaden retatrutide’s label and commercial positioning.

TRIUMPH-6: Weight Maintenance

TRIUMPH-6 addresses a critical question for any obesity drug: what happens when treatment is discontinued or reduced? The trial evaluates weight maintenance strategies, including dose reduction and treatment withdrawal.

Weight regain after discontinuation has been a significant concern across the GLP-1 class. Semaglutide’s STEP 4 trial showed rapid weight regain upon treatment withdrawal. If TRIUMPH-6 demonstrates durable weight maintenance with a reduced dose or after a defined treatment period, it would address one of the biggest clinical and commercial questions facing the obesity drug category.

Phase 2 Data: What We Already Know

The Phase 2 trial (published in The New England Journal of Medicine, 2023) established retatrutide as the most potent weight-loss compound in clinical development. At the highest dose (12 mg), participants lost 24.2% of body weight at 48 weeks — and the weight-loss curves had not plateaued, suggesting further reductions would occur with longer treatment.

Safety Signals: What the Data Show

Retatrutide’s safety profile is consistent with the GLP-1 receptor agonist class, but the dose-dependent discontinuation rates warrant attention. At the 12 mg dose, 18.2% of participants discontinued due to adverse events in Phase 2 — a higher rate than seen with tirzepatide (approximately 5–7% in SURMOUNT trials) or semaglutide (approximately 6–7% in STEP trials).

The most common adverse events were gastrointestinal: nausea, diarrhea, vomiting, and decreased appetite. These events were most frequent during dose escalation and generally decreased in severity and frequency over time. No unexpected safety signals outside the known GLP-1 class effects were identified.

At the 8 mg dose, the discontinuation rate was 12.2% — still higher than approved competitors but accompanied by 22.8% weight loss, which some researchers argue represents a favorable benefit-risk ratio. The Phase 3 TRIUMPH trials use optimized dose-escalation schedules designed to improve GI tolerability, and their results will provide the definitive safety dataset.

For a comprehensive analysis of retatrutide side effects and tolerability data, see our retatrutide side effects guide.

Path to FDA Approval

Eli Lilly has indicated plans to submit a New Drug Application (NDA) for retatrutide in 2026. The submission will be anchored by TRIUMPH-1 and TRIUMPH-2 data, with TRIUMPH-4 providing supplementary evidence for a potential knee OA comorbidity indication.

Assuming a standard 10–12-month FDA review cycle, a potential approval decision could come in 2027. Priority Review designation, if granted, could shorten this timeline by several months. The FDA has shown willingness to expedite reviews for obesity drugs — tirzepatide (Zepbound) and semaglutide (Wegovy) both received Priority Review.

Key milestones to watch: TRIUMPH-1 readout (2026), TRIUMPH-2 readout (2026), NDA submission announcement, and FDA acceptance of the filing. Track all pipeline milestones on our obesity drug approval tracker.