Semaglutide 2.4 mg shown to reduce heart failure with preserved ejection fraction in overweight/obese people without diabetes

People with overweight or obese have an increased risk of developing heart failure and atrial fibrillation but treatment strategies for this group of patients remain not established. While recent interests have emerged regarding the role of newer pharmacotherapy, especially the sodium glucose co-transporter 2 inhibitor (SGLT2i) to treat heart failure in people with or without type 2 diabetes, evidence based for overweight/obese people without diabetes is still unclear. To help clarify this research gap, the randomized STEP-HFpEF trial was presented at the 2023 Congress of the European Society of Cardiology and published simultaneously online in the New England J of Medicine.¹ The dual primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in the 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. The trial showed that for adults with heart failure with preserved ejection fraction (HFpEF) but without diabetes, significant improvements in their heart failure-related symptoms and physical limitations, exercise function, and weight loss when treated with a semaglutide 2.4 mg injected subcutaneously weekly for 52 weeks compared with placebo. An average 7.8-point incremental improvement in patients' scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated measure of symptoms and functional limitations, compared with controls who received placebo injections, as well as an average incremental weight loss from baseline compared with placebo of 10.7% was observed. In addition, the mean change in the 6-minute walk distance was 21.5 m with semaglutide and 1.2 m with placebo (estimated difference, 20.3 m; p < .001), while analysis of the hierarchical composite end point, semaglutide produced more wins than placebo (win ratio, 1.72; 95% CI, 1.37–2.15; p < .001). The results also showed the treatment's safety in these patients.

Overall, while this study did not report specific cardiovascular event end points, evidence from this study in combination with the ‘headline’ result from the SELECT study described previously, will form a basis for more aggressive management strategy to improve cardiovascular outcomes in people living with overweight or obesity.