The main finding
In one sentence: In adults with heart failure with preserved ejection fraction and obesity, tirzepatide lowered the combined risk of death from heart causes or worsening heart failure (9.9% versus 15.3%, hazard ratio 0.62) and improved symptom scores, but it did not reduce deaths on their own.
Group averages, not an individual prediction. A trial result describes what happened to a defined group over a defined time.
On this page
Why this study matters
Heart failure with preserved ejection fraction, often shortened to HFpEF, is a form of heart failure in which the heart pumps normally but does not fill or relax properly. It is strongly linked to a higher body weight. SUMMIT is the first large randomized trial to test whether tirzepatide (Zepbound, Mounjaro) changes heart failure outcomes in this group. It measured real events, not just weight.
Who was in the study
The trial randomized 731 adults with heart failure, an ejection fraction of at least 50%, and a body mass index, or BMI, of at least 30. Ejection fraction is the share of blood the heart pumps out with each beat, and 50% or more counts as preserved. BMI is a number that relates weight to height. In total, 364 people were assigned to tirzepatide and 367 to placebo. It was an international trial. Everyone was treated for at least 52 weeks, and the median follow-up was 104 weeks.
What the researchers did
This was a double-blind, randomized, placebo-controlled trial. Randomized means people were assigned by chance, here in a one-to-one split. Double-blind means neither participants nor researchers knew who received which treatment. A placebo is an injection that looks the same but contains no medicine. People received weekly tirzepatide injections at up to 15 mg, or placebo.
There were two primary outcomes. The first was a composite of death from heart causes or a worsening heart failure event, measured as time to the first such event and confirmed by an independent committee. The second was the change over 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score, or KCCQ-CSS. This questionnaire scores heart failure symptoms and daily function from 0 to 100, with higher scores meaning better quality of life.
What they found
Death from heart causes or a worsening heart failure event occurred in 36 people (9.9%) on tirzepatide and 56 people (15.3%) on placebo (R32-C55). The hazard ratio was 0.62, with a 95% confidence interval of 0.41 to 0.95. A hazard ratio compares how quickly events happen in one group versus another, and a value below 1 means fewer events on tirzepatide. A confidence interval is the range within which the true result most likely sits.
| Outcome | Tirzepatide (n = 364) | Placebo (n = 367) | Hazard ratio or difference (95% CI) |
|---|---|---|---|
| Death from heart causes or worsening heart failure | 36 (9.9%) | 56 (15.3%) | HR 0.62 (0.41 to 0.95) |
| Worsening heart failure events | 29 (8.0%) | 52 (14.2%) | HR 0.54 (0.34 to 0.85) |
| Death from heart causes | 8 (2.2%) | 5 (1.4%) | HR 1.58 (0.52 to 4.83) |
| KCCQ-CSS change at 52 weeks | +19.5 points | +12.7 points | 6.9 points (3.3 to 10.6) |
The composite result was driven by fewer worsening heart failure events. Deaths from heart causes were few in both groups, and the hazard ratio of 1.58 with a wide interval means the trial cannot say whether tirzepatide affected death rates either way. The result must not be described as a reduction in deaths.
Symptom scores improved more with tirzepatide: a difference of 6.9 points (95% CI 3.3 to 10.6) at 52 weeks. The published summary we reviewed does not report weight change.
Side effects and people who stopped
Side effects, mainly stomach and bowel symptoms, led to stopping the trial drug in 23 people (6.3%) on tirzepatide and 5 people (1.4%) on placebo (R32-C56). The published summary we reviewed does not report the overall number of people who stopped treatment in each group, or the rates of individual side effects.
What this study does not tell you
- The benefit was on a combined outcome and on worsening heart failure. The trial did not show fewer deaths.
- Everyone had HFpEF and a BMI of at least 30. The results do not describe people with other types of heart failure or with a lower BMI.
- The summary we reviewed does not report weight change or how much of the benefit related to weight loss.
- The number of events was modest for a trial measuring heart outcomes, and the confidence interval for the main result runs from 0.41 to 0.95, so the size of the benefit is uncertain.
- Results should not be lined up against other medicines' heart trials, such as SELECT, to rank them. The populations and outcomes differ.
- The trial was funded by the manufacturer, and we reviewed the abstract only.
What it means in Canada
For Canadian readers living with HFpEF and a higher body weight, SUMMIT is the first randomized evidence that tirzepatide changed heart failure events and symptoms in this group. It does not describe how the medicine is prescribed or paid for here. See tirzepatide in Canada, public drug coverage by province and compare services.
Common questions
Did tirzepatide reduce heart failure events in SUMMIT?
Death from heart causes or a worsening heart failure event occurred in 9.9% of the tirzepatide group and 15.3% of the placebo group (hazard ratio 0.62, 95% CI 0.41 to 0.95).
Did tirzepatide reduce deaths in SUMMIT?
No. Death from heart causes occurred in 2.2% on tirzepatide and 1.4% on placebo (hazard ratio 1.58, 95% CI 0.52 to 4.83), so the trial does not show a survival benefit.
Did people feel better on tirzepatide in SUMMIT?
At 52 weeks, the heart failure symptom score improved by 19.5 points with tirzepatide and 12.7 with placebo, a difference of 6.9 points (95% CI 3.3 to 10.6).
Related reading
Other studies in this library that bear on the same question.
SELECT heart failure subgroup: semaglutide
SELECT: semaglutide and heart attack or stroke
Tirzepatide versus insulin glargine in higher-risk diabetes: SURPASS-4
Tirzepatide for weight loss in adults without diabetes: SURMOUNT-1
Cochrane review of tirzepatide for adults with obesity
Source
Original paper: Milton Packer, SUMMIT, The New England journal of medicine, 2025. PubMed: https://pubmed.ncbi.nlm.nih.gov/39555826/. DOI: https://doi.org/10.1056/NEJMoa2410027. Funding: The trial was funded by Eli Lilly. How we summarized it: abstract and extracted data.
This page explains a published study. It is not medical advice and does not describe whether a medicine is right for you. Talk to your doctor, nurse practitioner or pharmacist about your own situation. Reviewed and signed by two pharmacists registered in British Columbia, 2026-09-18.
Evidence records behind this page
Each record is a row in the clinical evidence file, taken from the published paper named above. The caution column is the limit the researcher recorded for that number.
This table scrolls sideways.
| Record | What the paper reports | Type | Population | Caution | Source |
|---|---|---|---|---|---|
| R32-C55 | In SUMMIT, cardiovascular death or worsening heart failure occurred in 9.9% with tirzepatide versus 15.3% with placebo over a median 104-week follow-up (hazard ratio 0.62; 95% CI 0.41 to 0.95). | direct evidence | Adults with obesity and heart failure with preserved ejection fraction (at least 50%) | HFpEF with obesity population; composite benefit cannot be described as reduced cardiovascular mortality. Abstract-only. | PubMed 39555826 |
| R32-C56 | Adverse events led to stopping study drug in 6.3% receiving tirzepatide and 1.4% receiving placebo in SUMMIT. | direct evidence | Adults with obesity and heart failure with preserved ejection fraction (at least 50%) | HFpEF with obesity population; composite benefit cannot be described as reduced cardiovascular mortality. Abstract-only. | PubMed 39555826 |