SUMMIT: Tirzepatide in Heart Failure
Last verified May 2026 · Phase 3 · Finished; published late 2024 into early 2025 · NCT04847557 ↗
Heart failure with preserved ejection fraction is common, strongly associated with obesity, and has historically had very little that works. The obesity-related phenotype — where excess adipose tissue drives the hemodynamics — is the one these trials target. What distinguishes SUMMIT from STEP-HFpEF is the endpoint: STEP-HFpEF measured how people felt using a validated questionnaire, while SUMMIT measured whether they died or were hospitalized. Both matter; the second is harder to argue with.
- Enrollment
- 731
- Duration
- At least 52 weeks of treatment with a median 104 weeks of follow-up; symptoms measured at 52 weeks and events counted out to 160
- Drug
- Tirzepatide
- Population
- Adults with chronic heart failure, a pumping fraction of at least 50%, a BMI of 30 or above, raised NT-proBNP or structural changes visible on imaging, and symptoms limiting them day to day. ★ Unlike the semaglutide trial in this condition, diabetes was allowed and used to balance the arms — which is what made the subgroup finding below possible. Average weight around 105 kg at a BMI near 38, average age 65, and about 54% women, enrolled across ten countries spanning four continents.
Primary endpoint
Cardiac death or a worsening heart-failure event, whichever came first
Treatment arm
36/364 (9.9%)
Comparator
56/367 (15.3%)
Treatment difference: Hazard ratio 0.62 (95% CI 0.41 to 0.95; P=0.026)
★ This is the row that separates this trial from the semaglutide one: it counted events rather than feelings. ⚠ Read where the benefit came from — worsening heart failure fell from 14.2% to 8.0%, while cardiac deaths were few in both arms and numerically slightly higher on the drug. This trial shows fewer people getting worse; it does not show fewer people dying.
Secondary endpoints
| Endpoint | Treatment | Comparator | Difference |
|---|---|---|---|
| How much better people said they felt after a year, on a validated heart-failure questionnaire A gap of about 7 points, comfortably past the 5 points usually treated as meaningful — and closely matching what the semaglutide trial found, which is reassuring rather than redundant. | +19.5 points (SD 1.2) | +12.7 points (SD 1.3) | Between-group difference 6.9 points (95% CI 3.3 to 10.6; P<0.001) |
| How much further people could walk in six minutes Improved more than placebo, backing up the questionnaire with something measured by a stopwatch. | Increased on tirzepatide | Smaller change on placebo | Between-group difference approximately 18 meters favoring tirzepatide (P<0.001) |
| How much body weight came off About 14%, in line with what this drug does in ordinary weight trials — 12.9% in those without diabetes and 10.4% in those with it. | Approximately -13.9% | Approximately -2.2% | Between-group difference roughly -11.6 percentage points (P<0.001) |
| Inflammation in the blood ★ Fell, and — in the mechanistic analyses — the fall tracked closely with reduced heart-muscle injury and better walking distance. That is a chain of evidence, not a single marker moving. | Reduced | Smaller change | Estimated treatment difference -37.2% (95% CI -45.7 to -27.3; P<0.001) |
| NT-proBNP, the blood marker of cardiac strain ⚠ Down, but not by enough to reach statistical significance. Honest to report as a near miss rather than a result. | Reduced | Smaller change | Estimated treatment difference -10.5% (95% CI -20.7 to 1.0; P=0.07) |
| Top blood-pressure number A modest drop, feeding the argument that the drug is unloading pressure and volume from a stiff heart. | Reduced | Smaller change | Estimated treatment difference -5 mmHg (95% CI -7 to -3; P<0.001) |
| Troponin T, which rises when heart muscle is being damaged ★ Down. This one matters because it suggests the drug is affecting the heart muscle itself, not simply shifting fluid around. | Reduced | Smaller change | Estimated treatment difference -10.4% (95% CI -16.7 to -3.6; P=0.003) |
| Moved up a functional class — the standard grading of how limited someone is More people improved on the drug, which is the plain-language version of the questionnaire result. | Higher proportion improved | Lower proportion improved | Favors tirzepatide; magnitude similar in patients with and without diabetes in prespecified subgroup analysis |
Adverse events
| Event | Treatment rate | Comparator rate |
|---|---|---|
| Stopped the drug because of a side effect 6.3% against 1.4% on placebo, almost all stomach and bowel effects. | 23/364 (6.3%) | 5/367 (1.4%) |
| Nausea and other stomach problems Higher than placebo, matching the profile across this drug's whole trial program. | Higher on tirzepatide than placebo | Lower |
| Serious adverse events Similar in both arms, with nothing new appearing that earlier trials of this drug had not already seen. | Similar between arms | Similar |
Subgroup analyses
- People who also had type 2 diabetes: Cardiac events reduced by roughly a third, with a confidence interval crossing 1
They lost 10.4% of body weight against 12.9% in those without diabetes, yet symptom scores, walking distance and functional class improved by the same amount.
- People without diabetes: Cardiac events reduced by a near-identical amount
★ The finding worth carrying off this page: the two groups lost noticeably different amounts of weight and got the same cardiac benefit. Whatever is protecting the heart is not simply the weight coming off.
- Split by starting BMI and by how much fat sat around the middle: Both the event reduction and the symptom improvement held across every BMI band
Benefit did not require the heaviest patients, which matters for anyone whose coverage is decided by a BMI cutoff.
Clinical significance
Together with STEP-HFpEF, this establishes obesity-related HFpEF as a genuine indication for this class rather than an incidental benefit of weight loss. For readers with a heart-failure diagnosis, it is among the strongest coverage arguments available. ⚠ The population was specifically HFpEF with obesity; it does not extend to heart failure with reduced ejection fraction, which is a different disease with different treatment.
Who sells tirzepatide, and for how much
This trial tested Tirzepatide. Across the 556 sellers on this register, 253 publish a standing monthly cash price for compounded tirzepatide, from $99 a month, with a median of $240.
⛔ None of those sellers was in this trial. A compounded preparation is not the product studied here: no agency has reviewed that specific preparation for safety, effectiveness or manufacturing quality, and its concentration is set by whichever pharmacy filled it. The result above is the strongest evidence available for tirzepatide and it was generated on something else. Every seller, with its price record.
Frequently Asked Questions
References
- 1.Packer M, Zile MR, Kramer CM, et al.; SUMMIT Trial Study Group. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2025. PMID: 39555826.
- 2.U.S. National Library of Medicine. A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial. ClinicalTrials.gov, NCT04847557. 2025. https://clinicaltrials.gov/study/NCT04847557
- 3.Borlaug BA, Zile MR, Kramer CM, et al. Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial. Nat Med. 2025. PMID: 39551891.
- 4.Packer M, Zile MR, Kramer CM, et al.; SUMMIT Trial Study Group. Influence of Type 2 Diabetes on the Effects of Tirzepatide in Patients With Heart Failure and a Preserved Ejection Fraction With Obesity: A Prespecified Stratification-Based Analysis. J Am Coll Cardiol. 2025. PMID: 40903131.
- 5.Kramer CM, Borlaug BA, Zile MR, et al. Tirzepatide Reduces LV Mass and Paracardiac Adipose Tissue in Obesity-Related Heart Failure: SUMMIT CMR Substudy. J Am Coll Cardiol. 2025. PMID: 39566869.
- 6.Packer M, Zile MR, Borlaug BA, et al. Impact of Body Mass Index, Central Adiposity, and Weight Loss on the Benefits of Tirzepatide in HFpEF: The SUMMIT Trial. J Am Coll Cardiol. 2025. PMID: 40701669.