TRIUMPH-2 and TRIUMPH-3 Explained: Retatrutide in Diabetes and Heart Disease, Arm by Arm

Written by Olha Orlyk. Updated October 29, 2026.

TRIUMPH-2 and TRIUMPH-3 are the two Phase 3 trials that tested retatrutide in the people hardest to treat with weight-loss drugs: adults with type 2 diabetes, and adults with severe obesity and established heart disease. Both succeeded. In TRIUMPH-2, people with diabetes lost 20.8% of their body weight at 80 weeks on the 12 mg dose against 4.0% on placebo, and their HbA1c fell by 1.5 points. In TRIUMPH-3, people with a BMI of 35 or more and cardiovascular disease lost 22.6% against 3.2%, with triglycerides down 37%, systolic blood pressure down 9.3 mmHg and the inflammation marker hsCRP down by half. The results, announced by Eli Lilly on July 23, 2026, completed the evidence package for a US filing now planned for the first quarter of 2027. They also left one question open: TRIUMPH-3 counted 44 major cardiovascular events on retatrutide against 52 on placebo, a difference too small to prove protection. This guide goes through both trials arm by arm, explains what the heart data do and do not show, and sets the numbers against tirzepatide and semaglutide.

Every incretin drug loses some of its effect in people with type 2 diabetes. In the semaglutide programme, people without diabetes lost about 15% on Wegovy and people with diabetes about 10%; tirzepatide showed the same gap. A drug that wants to be first-line in obesity has to show it still works well in diabetes, and a drug that will be prescribed to millions of people with heart disease has to show it is at least safe for the heart. TRIUMPH-1, reported in May 2026, showed what retatrutide does in obesity without diabetes: 28.3% weight loss at 80 weeks. TRIUMPH-2 and TRIUMPH-3 answer the harder questions. The full four-trial picture is summarised in retatrutide news.

TRIUMPH-2 randomised 1,152 adults with type 2 diabetes and obesity or overweight, average weight 234.6 lb (106 kg), BMI 38.2 and HbA1c 7.7%, equally to retatrutide 4 mg, 9 mg, 12 mg or placebo for 80 weeks. The doses were reached by gradual escalation, as described in retatrutide dosage in clinical trials.

Three points stand out. First, 20.8% is among the largest losses reported in a Phase 3 trial of people with diabetes and obesity; tirzepatide's equivalent trial, SURMOUNT-2, reported about 15% at 72 weeks. Second, the 9 mg and 12 mg doses produced almost the same HbA1c fall, and 9 mg came close on weight, which suggests 9 mg may be the practical dose for many people with diabetes. Third, the discontinuation numbers are not a simple dose ladder: more people stopped 9 mg than 12 mg, a pattern that often reflects chance and the timing of dose escalation rather than a real difference between the doses.

TRIUMPH-3 enrolled 1,949 adults with a BMI of 35 or more and established cardiovascular disease, such as a previous heart attack, stroke or peripheral artery disease, with or without type 2 diabetes. Average weight was 245.6 lb (111 kg) and BMI 40.4. Participants were randomised in a 1:1:2 ratio to retatrutide 9 mg, retatrutide 12 mg or placebo for 80 weeks.

At the highest dose, cardiovascular risk factors moved in every direction a cardiologist would want: triglycerides fell 37.0%, non-HDL cholesterol 16.5%, systolic blood pressure 9.3 mmHg, waist circumference 7.5 inches, and high-sensitivity C-reactive protein, a marker of inflammation linked to heart risk, by 51.2%. Those are surrogate markers rather than events, but they are the markers that drove the heart benefit seen with semaglutide in the SELECT trial. The benefit-by-benefit picture is in retatrutide benefits.

TRIUMPH-3 was not designed as a cardiovascular outcomes trial, but it counted heart events as a pre-specified analysis. On the broad five-part measure, MACE-5 (cardiovascular death, heart attack, stroke, hospitalisation for unstable angina, or coronary revascularisation), 44 people on retatrutide had an event against 52 on placebo. Lilly reported this as a hazard ratio of 0.82, an 18% lower rate, with a 95% confidence interval of 0.55 to 1.22. The interval crosses 1.0, which means the trial cannot exclude anything from a 45% reduction to a 22% increase. On the narrower MACE-3 measure (cardiovascular death, heart attack, stroke), there were 27 events on retatrutide against 23 on placebo, a hazard ratio of 1.12 with an interval of 0.64 to 1.96. An on-treatment analysis, counting only people still taking the drug and not pre-specified, gave hazard ratios of 0.73 and 0.92.

The honest reading is that the numbers are reassuring on safety, since there is no sign that retatrutide harms the heart, and inconclusive on benefit. The trial was too small and too short to answer the question, which is why Lilly is running TRIUMPH-Outcomes, a dedicated cardiovascular trial expected around 2029. Semaglutide already has a proven 20% reduction in major events from SELECT, and tirzepatide has shown it is at least as safe as dulaglutide for the heart. Until TRIUMPH-Outcomes reports, retatrutide will have the biggest weight loss and the thinnest heart evidence of the three, a trade-off compared in retatrutide vs tirzepatide.

The side-effect profile matched the rest of the programme: nausea and diarrhea were the most common, mostly mild to moderate and concentrated in the escalation phase. In TRIUMPH-2, nausea rose from 13.7% on 4 mg to 28.0% on 12 mg, and diarrhea affected about a third of people on the higher doses against 13.2% on placebo. In TRIUMPH-3 the rates were similar on 9 and 12 mg. Discontinuation because of side effects was 7.7% to 13.5% at the top doses, roughly two to three times placebo, and a little lower than the 11.3% seen at 12 mg in TRIUMPH-1. Dysesthesia, an unusual skin-sensitivity effect that appeared in TRIUMPH-1, was not highlighted in the July release. The full side-effect picture is on our retatrutide side effects page.

Cross-trial comparisons are rough, because populations, durations and analysis methods differ, but the gap is large enough to be meaningful: retatrutide's weight loss in diabetes is about what tirzepatide achieves in people without diabetes. The broader comparison, including cost and availability, is in retatrutide vs Ozempic, Wegovy and Zepbound.

TRIUMPH-2 and TRIUMPH-3 show that retatrutide keeps most of its power in the groups where other drugs lose it: 20.8% weight loss with type 2 diabetes and 22.6% in severe obesity with heart disease, alongside large falls in HbA1c, triglycerides, blood pressure and inflammation. The heart-event count, 44 against 52, is reassuring but not proof of protection, and that question will not be answered until about 2029. For now the trials complete the case for approval, not the case that retatrutide is better for the heart than drugs already proven to be. What retatrutide is and how its third receptor works is explained in what is retatrutide, and how quickly the weight comes off in how fast retatrutide works.

This article summarizes company announcements and published trials for general information. Retatrutide is an investigational drug and is not available outside clinical trials.