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Randomized controlled trial

SUMMIT: tirzepatide for heart failure with obesity

Over a median follow-up of 104 weeks, cardiovascular death or worsening heart failure occurred in 36 patients on tirzepatide (9.9%) and 56 on placebo (15.3%) (hazard ratio 0.62; 95% CI, 0.41 to 0.95).

Packer M et al. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. New England Journal of Medicine, 2025. DOI: 10.1056/NEJMoa2410027

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Key facts

Drug
tirzepatide
Design
Randomized controlled trial
Participants
731
Duration
52 weeks
Funding
Eli Lilly
Registry
NCT04847557
Population
731 adults with heart failure (NYHA class II to IV), a left ventricular ejection fraction of 50% or more and a BMI of 30 or more, randomized to tirzepatide up to 15 mg once weekly (364) or placebo (367) for at least 52 weeks. According to the trial registry, people with diabetes could take part if their HbA1c was below 9.5%.
Primary outcome
Two primary objectives: the first event of the composite of cardiovascular death or worsening heart failure, confirmed by a committee and analyzed as time to first event, and the change at 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS, from 0 to 100, where more points mean better quality of life).

What it found

Over a median follow-up of 104 weeks, cardiovascular death or worsening heart failure occurred in 36 patients on tirzepatide (9.9%) and 56 on placebo (15.3%) (hazard ratio 0.62; 95% CI, 0.41 to 0.95). Worsening heart-failure events occurred in 8.0% versus 14.2% (hazard ratio 0.54; 95% CI, 0.34 to 0.85), and cardiovascular death in 2.2% versus 1.4% (hazard ratio 1.58; 95% CI, 0.52 to 4.83), a very wide interval because there were only 8 and 5 deaths. At 52 weeks, the KCCQ-CSS score improved by 19.5 points with tirzepatide and 12.7 with placebo (difference of 6.9 points; 95% CI, 3.3 to 10.6). Adverse events, mainly digestive, led 6.3% on tirzepatide and 1.4% on placebo to stop the drug.

Limitations

Funded by Eli Lilly, the maker of tirzepatide. With 731 participants and few deaths, it cannot show whether tirzepatide reduces cardiovascular mortality; the reduction in the composite outcome came mainly from worsening heart-failure events, which according to the registry included, besides hospital admissions, increases in oral diuretics. The improvement in symptoms is measured with a questionnaire that participants fill in themselves. It only included people with a BMI of 30 or more.

What it means for you

In people with heart failure with preserved ejection fraction and obesity, tirzepatide reduced the risk of cardiovascular death or worsening heart failure (9.9% versus 15.3%) and improved symptoms compared with placebo. The trial does not show that it reduces deaths. If you have heart failure, any change to your treatment should be decided by your cardiologist or doctor.

Further reading

Related trials

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    SURMOUNT-4 (post hoc analysis)

    After switching from tirzepatide to placebo, the more weight people regained between week 36 and week 88, the more their cardiometabolic parameters worsened: waist circumference increased by 0.8 cm in those who regained less than 25% of the weight lost and by 14.7 cm in those who regained 75% or more.

  • tirzepatide112 weeks

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    At week 112, weight had changed by −21.9% on the maximum tolerated dose of tirzepatide, −16.6% on 5 mg and −9.9% on placebo.

  • tirzepatide72 weeks

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    At 72 weeks, weight changed by −21.3%, fat mass by −33.9% and lean mass by −10.9% with tirzepatide, compared with −5.3%, −8.2% and −2.6% on placebo.

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Sources

The original paper and the records consulted for this summary, with the date they were accessed.

  1. New England Journal of Medicine.Packer M, et al. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2025;392(5):427-437.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 39555826 (abstract).accessed .
  3. ClinicalTrials.gov (National Library of Medicine).ClinicalTrials.gov record NCT04847557 (eligibility and definition of heart-failure events).accessed .