TRIUMPH-2 and TRIUMPH-3 Results: Retatrutide in Diabetes and Heart Disease

On July 23, 2026, Eli Lilly announced topline results from the last two pivotal obesity trials of retatrutide (LY3437943): TRIUMPH-2, in adults with type 2 diabetes and obesity or overweight, and TRIUMPH-3, in adults with severe obesity and established cardiovascular disease. Both met their primary endpoints. With these two readouts the TRIUMPH program is complete, and Lilly used the same release to give a filing date: a Biologics License Application (BLA) to the FDA in the first quarter of 2027 for obesity, knee osteoarthritis pain and obstructive sleep apnea.

This post covers what was reported, what was not, and what it means for the approval timeline. Trial-level detail is on the TRIUMPH-2 and TRIUMPH-3 pages.

TRIUMPH-2: obesity with type 2 diabetes

TRIUMPH-2 enrolled 1,152 adults with type 2 diabetes and a BMI of 27 or higher, and followed them for 80 weeks. At baseline they weighed a mean of 106.4 kg (234.6 lb), had a mean BMI of 38.2, and a mean A1C of 7.7%.

Figures are the efficacy estimand (participants assumed to stay on treatment without prohibited weight-management or glycemic rescue therapy).

Three things are worth noticing. The 9 mg and 12 mg arms are less than two percentage points apart on weight, and the A1C effect is actually flat between them, so the top dose bought little extra glycemic benefit in this trial. The placebo group lost 4.0%, nearly double the 2.2% in TRIUMPH-1, which is what you expect when a diabetes population gets intensive background care. And the headline number, while about seven points below TRIUMPH-1’s -28.3%, is the largest ever reported in a Phase 3 obesity trial restricted to people with diabetes; for context, tirzepatide reached -14.7% in SURMOUNT-2 and semaglutide 2.4 mg reached -9.6% in STEP 2, both cross-trial comparisons.

The nested obstructive sleep apnea basket, the trial’s second primary endpoint, was not reported in the topline release.

TRIUMPH-3: severe obesity with cardiovascular disease

TRIUMPH-3 enrolled 1,949 adults with a BMI of 35 or higher and established cardiovascular disease, with or without diabetes, for 80 weeks. Baseline weight was 111.4 kg (245.6 lb) and baseline BMI 40.4. Only the 9 mg and 12 mg doses were tested.

At 12 mg, triglycerides fell 37.0%, non-HDL cholesterol 16.5%, systolic blood pressure 9.3 mmHg, waist circumference 7.5 inches (19.0 cm) and hsCRP 51.2%. Those are the largest cardiometabolic marker changes reported anywhere in the retatrutide program.

The cardiovascular event data

Because every participant had cardiovascular disease, TRIUMPH-3 adjudicated major adverse cardiovascular events during the study. This was exploratory; the trial was powered for weight, not events.

• MACE-5 (cardiovascular death, heart attack, stroke, hospitalization for unstable angina or heart failure): 44 events on retatrutide versus 52 on placebo, hazard ratio 0.82 (95% CI 0.55–1.22).
• MACE-3 (cardiovascular death, heart attack, stroke): 27 versus 23, hazard ratio 1.12 (95% CI 0.64–1.96).

Neither is statistically significant, and both intervals include both benefit and harm. The honest summary is that there is no signal of excess events in a high-risk population despite retatrutide’s known resting heart-rate increase, and no proof of benefit either. The definitive answer will come from TRIUMPH-Outcomes, the roughly 10,000-participant cardiovascular outcomes trial that is still running. Until then, comparisons with semaglutide’s SELECT result (a 20% MACE reduction over about three years) are premature.

Safety across both trials

Gastrointestinal events were, as always, the most common: diarrhea in 33.6% (TRIUMPH-2) and 24.4% (TRIUMPH-3) of 12 mg participants, nausea in 28.0% and 22.4%, constipation in 16.8% and 15.7%.

The number most people were watching was dysesthesia, the abnormal skin-sensation side effect that appeared in 20.9% of 12 mg participants in TRIUMPH-4 and 12.5% in TRIUMPH-1. In these two trials it was 7.3% (TRIUMPH-2) and 6.4% (TRIUMPH-3) at 12 mg, against 0.7% and 1.3% on placebo. The program-wide picture is now four trials at 12 mg ranging from 6.4% to 20.9%, with the two lowest rates in the trials that included people with diabetes. Why diabetes would blunt the effect is not known. Our dysesthesia explainer has the full comparison.

Discontinuation because of adverse events at 12 mg was 7.7% in TRIUMPH-2 and 13.5% in TRIUMPH-3. TRIUMPH-2’s 9 mg arm discontinued more often (11.6%) than its 12 mg arm, an oddity the topline release does not explain.

What changed in the timeline

Before July 23, Lilly’s guidance was a submission “in late 2026 to early 2027”, and most coverage, including ours, assumed a New Drug Application. The release changed both parts:

1. The application is a BLA, not an NDA. Lilly’s position is that retatrutide, a 41-amino-acid peptide, is a biologic. A BLA carries 12 years of data exclusivity rather than five and takes the product outside the pharmacy-compounding provisions that apply to drugs. The FDA has disputed the classification in court, and the dispute is unresolved (Lilly’s appeal in Eli Lilly v. Kennedy is pending before the Seventh Circuit). Lilly’s chief executive said on the August 5 earnings call that the company would “hope to come to a conclusion with the FDA to support a BLA application”.
2. The date is Q1 2027. On the same call Lilly said it needed “a little bit more on the CMC side”, meaning manufacturing and quality-control data, before submitting. The clinical package is described as complete.

Working forward from a first-quarter 2027 submission: the FDA takes 60 days to accept an application for filing, then ten months under standard review or six under priority review. That puts the earliest realistic decision in late 2027 with priority review, and the base case in the first half of 2028. Our approval timeline has been updated accordingly.

What was not in the release

• Treatment-regimen (intention-to-treat) weight figures for either trial
• The TRIUMPH-2 OSA basket result
• Responder rates (the share of participants losing 5%, 10%, 15% or more)
• Heart-rate changes
• Any pricing or launch commentary, which Lilly has still not given

What comes next

• September 30, 2026: full TRIUMPH-2 results at an EASD-sponsored symposium at the EASD Annual Meeting in Milan (08:30–09:30 CEST).
• TRIUMPH-3 full presentation: Lilly has said the data will be presented at future meetings and published; no date yet.
• Q1 2027: planned BLA submission.
• Ongoing: TRIUMPH-Outcomes, TRANSCEND-T2D-2 (head-to-head against semaglutide), the SYNERGY/MACELD liver program and a chronic low-back-pain study.

Retatrutide remains investigational and unapproved. The only legitimate routes to the drug are clinical trials and, since August 2026, Lilly’s narrow expanded access program for people with severe, refractory obesity.