Semaglutide as new treatment for obese patients with heart failure and preserved ejection fraction

Nasser Mikhail

Published on: 2023-10-10

Abstract

Whether pharmacological therapy targeting weight loss leads to amelioration of exercise tolerance in obese patients with heart failure and preserved ejection fraction (HFpEF) is unclear. The STEP-HFpEF (Semaglutide Treatment Effect in People with Obesity and HFpEF) was a randomized, double-blind placebo control trial designed to study the effects of semaglutide (2.4 mg given subcutaneously once a week) on exercise capacity in obese patients with HFpEF. The dual primary end points of STEP-HFpEF were the changes in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and body weight. At 52 weeks, the mean value of the KCCQ-CSS score increased by 16.6 and 8.7 points in the semaglutide and placebo groups, respectively; the estimated difference was 7.8 points (95% CI, 4.8 to 10.9; P<0.001). The mean percentage decreases in body weight were -13.3% and -2.6% in the semaglutide and placebo groups, respectively, with an estimated difference of -10.7% (95% CI, -11.9 to -9.4; P<0.001). The 6-minute walk distance (6MWD) increased by 21.5 meters (m) and 1.2 m in the semaglutide and placebo groups, respectively; the estimated difference was 20.3 m (95% CI, 8.6 to 32.1, P < 0.001). Semaglutide therapy was associated with a greater decrease in serum levels of C-reactive protein (CRP) (43.5% reduction) compared with placebo (7.3% reduction) (P<0.001). There was a direct relationship between the magnitude of weight loss and amelioration in KCCQ-CSS, 6MWD, and a reduction in CRP levels. Rates of discontinuation of semaglutide due to adverse effects, mainly gastrointestinal (GE), were higher than placebo, 13.3% and 5.3%, respectively. In conclusion, semaglutide (2.4 mg/week) is effective in improving exercise tolerance in obese patients with HFpEF.