Retatrutide TRIUMPH-2 and TRIUMPH-3 Report: Diabetes and Cardiovascular Phase 3 Results
TL;DR: Retatrutide's TRIUMPH-2/3 reported 23 July 2026: up to 20.8%/22.6% weight loss; TRIUMPH-3's MACE data stayed inconclusive.
What Did Eli Lilly Announce on 23 July 2026?
Eli Lilly reported topline Phase 3 results for two remaining studies in retatrutide's (LY3437943) TRIUMPH programme — TRIUMPH-2 and TRIUMPH-3 — on 23 July 2026, one day before this article's publication date.[1] Our own coverage flagged both trials as pending just a week earlier, alongside a note that neither would resolve retatrutide's cardiovascular safety question on its own.[2] That prediction held: both trials met their weight-loss primary endpoints, but TRIUMPH-3's cardiovascular sub-analysis came back statistically inconclusive, not reassuring or concerning in either direction.
With this release, four of the five TRIUMPH-branded studies plus the separately branded TRANSCEND-T2D-1 diabetes trial have now reported. Only the dedicated, event-driven cardiovascular and kidney outcomes trial (NCT06383390, roughly 10,000 participants) remains, and it is not expected before 2027 at the earliest.
What Were TRIUMPH-2's Results in Type 2 Diabetes and Obesity?
Design: Randomised, double-blind, placebo-controlled trial in 1,152 adults with both type 2 diabetes and obesity or overweight — a co-occurring population TRIUMPH-1 excluded — with a mean baseline weight of 234.6 lb (106.4 kg) and mean A1C of 7.7%, followed to 80 weeks.[1]
Weight change: Mean loss of 29.8 lb (12.7%) on 4 mg, 45.4 lb (19.1%) on 9 mg and 49.6 lb (20.8%) on 12 mg.
Glycaemic control: A1C reductions of up to 1.6 percentage points on the highest dose.
Tolerability: Discontinuation due to adverse events was 3.8% (4 mg), 11.6% (9 mg) and 7.7% (12 mg), versus 4.9% on placebo.
Source: Eli Lilly, 23 July 2026 · ClinicalTrials.gov NCT05929079
TRIUMPH-2's 20.8% headline figure sits below TRIUMPH-1's 28.3% mean weight loss in adults without diabetes, a gap consistent with a pattern already documented across the GLP-1 class: people with type 2 diabetes tend to lose proportionally less weight on incretin therapies than people without it. The 11.6% adverse-event discontinuation rate on the 9 mg dose — higher than either the 4 mg or 12 mg arms — is a non-monotonic pattern Lilly has not yet explained in the topline release; a fuller tolerability breakdown typically follows at a subsequent medical conference.
What Were TRIUMPH-3's Results in Cardiovascular Disease and Obesity?
Design: An 80-week weight-management trial in 1,949 adults with a BMI of 35 kg/m² or higher and established cardiovascular disease, with or without type 2 diabetes.[1]
Weight change: Mean loss of 52.7 lb (21.6%) on 9 mg and 55.8 lb (22.6%) on 12 mg, versus 7.7 lb (3.2%) on placebo.
Cardiometabolic markers (12 mg): Triglycerides −37.0%, non-HDL cholesterol −16.5%, systolic blood pressure −9.3 mmHg, waist circumference −7.5 in, high-sensitivity CRP −51.2%.
Source: Eli Lilly, 23 July 2026 · ClinicalTrials.gov NCT05882045
Does TRIUMPH-3 Resolve Retatrutide's Cardiovascular Safety Question?
No, and this is the detail trade-press coverage flagged as the real story behind TRIUMPH-3's headline weight-loss number.[3] TRIUMPH-3's pre-specified in-study cardiovascular analysis reported 44 major adverse cardiovascular events (MACE-5, the broader five-component composite) in participants randomised to retatrutide versus 52 on placebo — a hazard ratio of 0.82 (95% CI 0.55–1.22). A narrower MACE-3 composite reported 27 events on retatrutide versus 23 on placebo — a hazard ratio of 1.12 (95% CI 0.64–1.96). Both confidence intervals cross 1, meaning neither result rules out benefit or harm; the trial's event rate came in lower than the design anticipated, leaving the in-study MACE analysis underpowered by the numbers actually observed.
This directly echoes the arrhythmia imbalance we covered in TRANSCEND-T2D-1[4] (7 of 403 retatrutide participants versus 0 of 134 on placebo): individual trials keep surfacing cardiovascular data points that are suggestive but not statistically definitive in either direction. The study built specifically to answer the cardiovascular question — a dedicated, event-driven outcomes trial enrolling roughly 10,000 participants with atherosclerotic cardiovascular disease and/or chronic kidney disease — remains the one to watch, and its completion still depends on event accrual rather than a calendar date.[5]
| Trial | Population | Headline result (12mg, 80–104 wk) | Status |
|---|---|---|---|
| TRIUMPH-1 | Obesity/overweight, no diabetes | 28.3% weight loss | Reported 21 May 2026 |
| TRIUMPH-4 | Obesity/overweight + knee OA | 28.7% weight loss | Reported Dec 2025 |
| TRANSCEND-T2D-1 | Type 2 diabetes | −2.0pp A1C | Published Lancet 6 Jun 2026 |
| TRIUMPH-2 | Obesity/overweight + type 2 diabetes | 20.8% weight loss | Reported 23 Jul 2026 |
| TRIUMPH-3 | Obesity/overweight + cardiovascular disease | 22.6% weight loss; MACE inconclusive | Reported 23 Jul 2026 |
| Outcomes trial (NCT06383390) | ASCVD and/or chronic kidney disease | MACE & kidney events (powered) | Event-driven, not before 2027 |
What Does This Mean for Retatrutide's FDA Filing Timeline?
Eli Lilly's 23 July 2026 release states the company plans to submit a Biologics License Application (BLA) for retatrutide to the FDA in Q1 2027, incorporating TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, TRIUMPH-4 and TRANSCEND-T2D-1 data.[1] That is a later window than the Q4 2026 filing target reported in earlier trade-press coverage — see our FDA approval timeline guide for the fuller regulatory picture — and it still will not include mature, statistically powered cardiovascular-outcomes data, since the dedicated CVOT will not have reported by then. Regulators have accepted this sequencing before: obesity and diabetes drugs routinely reach approval on efficacy and short-term safety data with a post-marketing cardiovascular-outcomes commitment attached, the same path semaglutide and tirzepatide followed.
What Should UK Researchers Take From This?
None of the results reported here change retatrutide's UK regulatory status: it remains an unlicensed, investigational compound with no MHRA marketing authorisation, and nothing in this trial summary constitutes a therapeutic or health claim. Velox Peptides supplies retatrutide strictly as an HPLC-verified in vitro research reagent, with no health or therapeutic claims made for it.
This compound is supplied as a research reagent only. It is not a medicine and has not been evaluated by the MHRA or FDA for use in our products. Not for human or veterinary use. See our Research Use Policy and MHRA Statement.
References
- Eli Lilly and Company. “Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C.” 23 July 2026. investor.lilly.com
- Velox Peptides. “Retatrutide TRIUMPH-2 & TRIUMPH-3: What's Left.” 16 July 2026. veloxpeps.com
- Fierce Biotech. “Lilly's triple-G drug hits 22.6% weight loss, but impact on reducing cardio risk is less clear.” 23 July 2026. fiercebiotech.com
- Bajaj HS, et al. Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial. The Lancet, 2026. PMID: 42250575
- ClinicalTrials.gov. The Effect of Retatrutide Once Weekly on Cardiovascular Outcomes and Kidney Outcomes in Adults Living With Obesity (TRIUMPH-Outcomes). NCT06383390
Frequently Asked Questions
What did retatrutide's TRIUMPH-2 and TRIUMPH-3 trials report?
Eli Lilly announced topline Phase 3 results for both trials on 23 July 2026. TRIUMPH-2, in adults with type 2 diabetes and obesity, reported up to 20.8% mean weight loss at 80 weeks on the 12 mg dose, alongside A1C reductions of up to 1.6 percentage points. TRIUMPH-3, in adults with obesity and established cardiovascular disease, reported up to 22.6% mean weight loss at 80 weeks on the 12 mg dose.
Does TRIUMPH-3 prove retatrutide reduces cardiovascular risk?
No. TRIUMPH-3's pre-specified in-study analysis of major adverse cardiovascular events (MACE) was underpowered and statistically inconclusive: the MACE-5 hazard ratio was 0.82 (95% CI 0.55–1.22) and the MACE-3 hazard ratio was 1.12 (95% CI 0.64–1.96), with both confidence intervals crossing 1. A dedicated, event-driven cardiovascular and kidney outcomes trial (NCT06383390, roughly 10,000 participants) is the study statistically designed to answer that question, and it is not expected to read out before 2027 at the earliest.
What were the discontinuation rates in TRIUMPH-2?
Discontinuation due to adverse events in TRIUMPH-2 was 3.8% on the 4 mg dose, 11.6% on 9 mg and 7.7% on 12 mg, compared with 4.9% on placebo, according to Eli Lilly's 23 July 2026 topline release.
Does this change retatrutide's FDA filing timeline?
Eli Lilly's 23 July 2026 release states the company plans to submit a Biologics License Application (BLA) for retatrutide to the FDA in Q1 2027, incorporating data from TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, TRIUMPH-4 and TRANSCEND-T2D-1. This is later than the Q4 2026 NDA target reported in earlier trade-press coverage; it remains an investigational compound with no marketing authorisation anywhere.
Is retatrutide legal to buy in the UK for research?
Yes. Retatrutide is legal to purchase in the UK for in vitro research purposes. It is not licensed as a medicine and is not approved for human use anywhere. Velox Peptides supplies retatrutide strictly as a research reagent in accordance with its Research Use Policy.