Compared with placebo in the STEP-HFpEF trial, once-weekly semaglutide 2.4 mg reduced symptoms and physical limitations, improved exercise function, and produced weight loss, investigators report. “The data from our trial extend these findings and indicate that weight loss with semaglutide at a dose of 2.4 mg is a beneficial strategy in patients with heart failure with preserved ejection fraction and obesity,” the group concludes. “Whether this is also the case with other types of weight loss interventions or in other populations (such as those with heart failure with reduced ejection fraction and obesity) will be useful to evaluate in future trials.”
The 529 participants had BMIs of 30 or higher and were randomized to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. Dual primary endpoints of the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; higher scores indicating fewer symptoms and physical limitations) and the change in body weight produced these outcomes: “The mean change in the KCCQ-CSS was 16.6 points with semaglutide and 8.7 points with placebo (estimated difference, 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; P <0.001), and the mean percentage change in body weight was −13.3% with semaglutide and −2.6% with placebo (estimated difference, −10.7 percentage points; 95% CI, −11.9 to −9.4; P <0.001). 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; 95% CI, 8.6 to 32.1; P <0.001). In the analysis of the hierarchical composite end point, semaglutide produced more wins than placebo (win ratio, 1.72; 95% CI, 1.37 to 2.15; P<0.001). The mean percentage change in the [C-reactive protein] level was –43.5% with semaglutide and –7.3% with placebo (estimated treatment ratio, 0.61; 95% CI, 0.51 to 0.72; P <0.001). Serious adverse events were reported in 35 participants (13.3%) in the semaglutide group and 71 (26.7%) in the placebo group.”
Editorial: “One may propose that the success of SGLT2 inhibition and now of GLP-1 agonism suggests that an important part of heart failure with preserved ejection fraction is driven by metabolic abnormalities,” writes an editorialist. “However, SGLT2 inhibition is also known to be beneficial in patients with heart failure with reduced ejection fraction. Whether GLP-1 agonism is also beneficial in these patients has not yet been directly addressed, but a meta-analysis suggested that GLP-1 agonists have modest benefits for heart failure end points. If indeed SGLT2 inhibition and GLP-1 agonism prove beneficial in patients with heart failure regardless of whether the ejection fraction is reduced or preserved, then the two forms of heart failure might have more in common than is often assumed.…”