Research Summary

Semaglutide Provides Benefits for Patients With HFpEF and Obesity

Anthony Calabro, MA

In a randomized, double-blind, placebo-controlled study, researchers found that semaglutide 2.4 mg, a glucagon-like peptide 1 receptor agonist that is FDA approved for long-term weight management, led to reductions in symptoms and physical limitations, improvements in exercise function, and weight loss compared with placebo for patients with heart failure with preserved ejection fraction (HFpEF) and obesity (BMI ≥ 30).

HFpEF is associated with more than half of all cases of heart failure in the United States. Most patients with HFpEF have obesity or overweight, which plays a major role in the development of the condition. To date, no approved treatments specifically target HFpEF in patients with obesity.

Enter Kosiborod and colleagues, who investigated the effects of once-weekly semaglutide 2.4 mg vs placebo over a 52-week period in patients with HFpEF and a BMI of 30 or higher.

Between March 2021 and March 2022, researchers conducted the Effect of Semaglutide 2.4 mg Once Weekly on Function and Symptoms in Subjects with Obesity-related Heart Failure with Preserved Ejection Fraction (STEP-HFpEF) trial in 13 countries in Asia, Europe, and North and South America. The STEP-HFpEF trial enrolled a total of 529 patients with HFpEF and obesity, and these patients were randomly assigned in a 1:1 ratio.

The trial had dual primary endpoints: the change in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), which measures symptom severity and physical limitations (scores range from 0 to 100, with higher scores indicating fewer symptoms and limitations) and change in body weight.

The results indicated improvements in the patients receiving semaglutide compared with those on placebo. The mean change in the KCCQ-CSS was 16.6 points in the semaglutide group and 8.7 points in the placebo group (estimated difference, 7.8 points; 95% CI, 4.8 to 10.9; p < 0.001). A greater change in body weight was also noted, with a mean percentage change of -13.3% in the semaglutide group and -2.6% in the placebo group (estimated difference, -10.7 percentage points; 95% CI, -11.9 to -9.4; p < 0.001).

Serious adverse events were documented, although they occurred less often in the semaglutide group compared with the placebo group (13.3% and 26.7%, respectively). This study also had limitations, namely that the trial was not powered to investigate the impact of semaglutide on hospitalizations for heart failure. The study was funded by Novo Nordisk.

Still, the researchers found that their study results could potentially impact patients with HFpEF and obesity.

“In adults with heart failure with preserved ejection fraction and obesity, once-weekly treatment with semaglutide was associated with greater reductions in heart failure-related symptoms and physical limitations and greater weight loss than placebo over 52 weeks,” the authors concluded.

Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389:1069-1084. doi:10.1056/NEJMoa2306963