STEP-HFpEF

Heart failure with preserved ejection fraction is a frustrating diagnosis. The heart squeezes normally on an echocardiogram, but it stiffens and fills poorly, and patients are breathless, swollen and exhausted. Before STEP-HFpEF, no therapy had been approved to target the obesity-related form of it specifically.

The trial randomized 529 adults with HFpEF and a BMI of 30 or higher to semaglutide 2.4 mg weekly or placebo for 52 weeks. It had two co-primary endpoints, which tells you something about the intent: change in symptoms, measured with the KCCQ-CSS questionnaire, and change in body weight. Kosiborod and colleagues published it in the New England Journal of Medicine in 2023.

Both were met. Mean KCCQ-CSS rose 16.6 points on semaglutide versus 8.7 on placebo (estimated difference 7.8 points). Body weight fell 13.3% versus 2.6%. Six-minute walk distance improved by 21.5 meters versus 1.2. C-reactive protein, a marker of inflammation, dropped 43.5% versus 7.3%. And serious adverse events were less common on semaglutide — 13.3% versus 26.7% — which is unusual and consistent with fewer heart-failure events.

Note what the trial did not show. It was not powered for hospitalizations or deaths; it measured how people felt and functioned over a year. That is a legitimate goal in a symptom-dominated disease, but it is a different claim from preventing events. The tirzepatide counterpart, SUMMIT, followed with its own design.

Worth asking your clinician: whether your heart failure is being attributed to obesity as a driver rather than an incidental finding, whether your diuretic dose will need adjusting as weight comes off, and how your symptoms will be tracked over time. Our STEP-HFpEF deep dive, heart-failure questions hub, and cardiovascular study roundup go further.