The short answer: Retatrutide has one dedicated cardiovascular outcomes trial, TRIUMPH-Outcomes (NCT06383390). It is a placebo-controlled study of about 10,000 adults with obesity and heart or kidney disease, and ClinicalTrials.gov estimates primary completion in February 2029. A separate trial, TRIUMPH-3, enrolled people with heart disease but measured weight loss, and its small count of heart events settled nothing. So far, no trial has shown that retatrutide prevents heart attacks or strokes.

What is TRIUMPH-Outcomes?

TRIUMPH-Outcomes is Eli Lilly's heart and kidney outcomes trial for retatrutide. Its ClinicalTrials.gov record describes a phase 3, randomized, double-blind, placebo-controlled, event-driven study. "Event-driven" means the trial runs until enough heart or kidney events happen to answer the question.

Key facts from the registry record:

  • Who: adults with a BMI of 27 or higher plus atherosclerotic cardiovascular disease, chronic kidney disease, or both. People with or without type 2 diabetes can join.
  • Qualifying disease: coronary artery disease, cerebrovascular disease, peripheral artery disease, or kidney disease defined by eGFR and urine albumin cutoffs.
  • Size: about 10,000 participants (an estimate, not a final count).
  • Treatment: weekly retatrutide injections raised to the maximum tolerated dose, or matching placebo.
  • Timeline: started April 30, 2024. Estimated primary completion is February 2029. Status is active, not recruiting.
  • Length: about 5 years, with follow-up of roughly 248 weeks.

The trial has two primary endpoints. The first is time to a nonfatal heart attack, nonfatal stroke, cardiovascular death, or a hospital stay or urgent visit for heart failure. The second is a kidney composite: end-stage kidney disease, a sustained drop of 40% or more in eGFR, cardiovascular death, or kidney death.

Secondary endpoints include classic three-point MACE (cardiovascular death, heart attack, or stroke) and death from any cause. A smaller phase 2b study, TRANSCEND-CKD, measured kidney function directly in 146 people. Its design paper says it will help interpret TRIUMPH-Outcomes.

Did TRIUMPH-3 show heart protection?

No. TRIUMPH-3 (NCT05882045) enrolled adults with a BMI of 35 or higher and a prior heart attack, prior stroke, or symptomatic peripheral artery disease. Its primary endpoint was percent change in body weight at 80 weeks, not heart events.

Lilly announced topline results on July 23, 2026. The trial randomized 1,949 people to 9 mg, 12 mg, or placebo in a 1:1:2 ratio, so pooled retatrutide and placebo groups were similar in size. Weight fell by 21.6% and 22.6% on the two doses, versus 3.2% on placebo.

Lilly also reported prespecified heart event counts. Events were less frequent than expected in both groups:

  • MACE-5 (death from any cause, heart attack, stroke, heart failure event, or coronary revascularization): 44 events on retatrutide versus 52 on placebo. Hazard ratio 0.82 (95% CI 0.55 to 1.22).
  • MACE-3 (cardiovascular death, heart attack, or stroke): 27 events on retatrutide versus 23 on placebo. Hazard ratio 1.12 (95% CI 0.64 to 1.96).

Both confidence intervals cross 1.0. That means the trial cannot show benefit or harm on heart events. These are topline figures from a press release, not a peer-reviewed paper.

What did trials show for blood pressure, lipids and heart rate?

Risk factors moved in a favorable direction. In TRIUMPH-3, Lilly reported that the highest dose lowered triglycerides by 37.0%, non-HDL cholesterol by 16.5%, systolic blood pressure by 9.3 mmHg, and hsCRP (an inflammation marker) by 51.2%.

The phase 2 data point the same way. A 2026 meta-analysis of randomized trials found that, compared with control groups, retatrutide lowered:

  • Systolic blood pressure by 6.79 mmHg
  • Diastolic blood pressure by 2.46 mmHg
  • Total cholesterol by 21.88 mg/dL
  • LDL cholesterol by 13.10 mg/dL
  • Triglycerides by 40.90 mg/dL

HDL cholesterol did not change. A post hoc analysis by Lilly scientists of the two phase 2 trials found apolipoprotein B fell by up to 24.2%. In the obesity trial without diabetes, hsCRP fell by 54.8%.

Heart rate is the open question. The phase 2 obesity trial in the New England Journal of Medicine reported dose-dependent increases in heart rate that peaked at 24 weeks and declined after that. See our retatrutide side effects guide for the wider safety picture.

Why do cardiovascular outcome trials matter?

Better numbers on a lab report do not guarantee fewer heart attacks. Only an outcomes trial counts the events themselves.

The FDA's January 2025 draft guidance on weight-reduction drugs asks sponsors to monitor blood pressure, heart rate, lipids, glucose, and ECGs. It says programs should include a comprehensive cardiovascular assessment, generally including ambulatory blood pressure monitoring. It adds that a cardiovascular outcomes trial may be necessary if a signal for cardiovascular risk appears. Whether that trial comes before or after approval depends on the signal.

The guidance also notes that some past weight-loss drug trials failed to show benefit on clinical outcomes. So a completed outcomes trial is the only way to earn a heart-protection claim on a label.

How do SELECT and SURPASS-CVOT compare?

Two finished trials show what retatrutide's program is aiming for.

SELECT (semaglutide). The SELECT trial enrolled 17,604 adults aged 45 or older with heart disease, a BMI of 27 or higher, and no diabetes. The primary endpoint occurred in 6.5% on semaglutide 2.4 mg and 8.0% on placebo. The hazard ratio was 0.80 (95% CI 0.72 to 0.90) over a mean follow-up of 39.8 months. More on semaglutide is at ozempic.md.

SURPASS-CVOT (tirzepatide). The SURPASS-CVOT trial randomized 13,299 adults with type 2 diabetes and atherosclerotic heart disease. It compared tirzepatide with dulaglutide, an active drug already shown to cut heart events, rather than placebo. The primary endpoint occurred in 12.2% versus 13.1%, a hazard ratio of 0.92 (95.3% CI 0.83 to 1.01). Tirzepatide was noninferior, but the superiority test was not significant.

TRIUMPH-Outcomes is closer to SELECT in design: placebo-controlled, in people with established disease. It differs in two ways. It includes people with diabetes, and it adds kidney disease as both an entry route and a primary endpoint.

What does this mean for approval?

Retatrutide is not FDA approved. Lilly said in July 2026 that it plans to submit a Biologics License Application in the first quarter of 2027. The company tied that filing to obesity, knee osteoarthritis pain, and obstructive sleep apnea. TRIUMPH-Outcomes will not finish before that filing.

In practice, any first approval would cover weight management, not heart protection. A cardiovascular claim would need TRIUMPH-Outcomes results, estimated at primary completion in 2029. Our FDA approval timeline covers the filing steps.

The bottom line

TRIUMPH-Outcomes is the trial that will answer whether retatrutide prevents heart attacks, strokes, and kidney decline. It is no longer recruiting, targets about 10,000 people, and is estimated to reach primary completion around February 2029. Until then, the evidence is limited to risk factors: lower blood pressure, triglycerides, non-HDL cholesterol, and inflammation markers, alongside a heart rate rise. TRIUMPH-3's event counts were too small to draw conclusions either way.

Last updated: September 2026. This article is for informational purposes only and does not constitute medical advice. Retatrutide is investigational; talk with your cardiologist or primary care clinician about proven ways to lower your heart risk.