SUMMIT

SUMMIT is the tirzepatide answer to STEP-HFpEF, and it went further than symptoms. It randomized 731 adults with heart failure with preserved ejection fraction and obesity to tirzepatide or placebo and followed them for a median of 104 weeks — twice as long as the semaglutide trial. Packer and colleagues published it in the New England Journal of Medicine in January 2025.

The primary composite was hard outcomes: death from cardiovascular causes or a worsening heart-failure event. It occurred in 36 of 364 patients (9.9%) on tirzepatide versus 56 of 367 (15.3%) on placebo, a hazard ratio of 0.62. Worsening heart-failure events alone fell from 14.2% to 8.0%. Cardiovascular deaths were few in both arms (8 versus 5), so the composite was driven by heart-failure events rather than mortality.

Symptoms improved too. At 52 weeks the KCCQ-CSS rose 19.5 points on tirzepatide versus 12.7 on placebo, a between-group difference of 6.9 points — very close to the 7.8-point difference STEP-HFpEF reported for semaglutide. Two different drugs, two different trials, strikingly similar symptom effects.

The distinction worth holding onto: STEP-HFpEF was powered to show people felt and functioned better; SUMMIT was powered to show fewer heart-failure events. Both matter, and they are not the same claim. Note also that Zepbound is not labeled for heart failure — its approved indications are weight management and moderate-to-severe obstructive sleep apnea in adults with obesity.

Worth asking your clinician: whether obesity is being treated as a driver of your heart failure, how diuretics should be adjusted as weight falls, and what warning signs of worsening heart failure to watch for. Our SUMMIT deep dive and heart-failure questions hub go further.