Dr. Cepeda Mora
Clinical question: Is semaglutide an effective heart failure treatment in patients with heart failure with preserved ejection fraction (HFpEF) and obesity?
Background: HFpEF is becoming more prevalent and commonly found in patients with obesity (BMI ≥30 kg/m2). Evidence suggests that obesity and adipose tissue may be a contributor to the development and progression of HFpEF. GLP-1 receptor agonists (GLP1RA) are effective weight loss medications, though it is unknown what clinical impact including symptom improvement they have on patients with HFpEF.
Study design: Randomized, double-blind, placebo-controlled trial
Setting: 96 sites in 13 countries in Asia, Europe, and North and South America
Synopsis: This study enrolled adult patients with obesity (BMI ≥30 kg/m2), HFpEF (left ventricular ejection fraction ≥45%; and New York Heart Association functional class II, III, or IV), a Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) of less than 90 points, a six-minute walk distance of at least 100 m; and clinical or laboratory evidence of volume-overloaded HF. About 500 participants, median age of 69, were randomized to receive semaglutide 2.4 mg subcutaneously weekly, versus placebo for 52 weeks. In patients randomized to receive semaglutide, there was an improvement in self-reported HF symptoms, with a mean change in KCCQ-CSS of 16.6 (versus 8.7 points in placebo) (95% CI, 4.8 to 10.9, P <0.001). There was also a significant difference in mean percent reduction in body weight with semaglutide (-13.3%) versus placebo (-2.6%) (95% CI, -11.9 to -9.4; P <0.001). Semaglutide participants also significantly improved in six-minute walk distance, 21.5 m versus 1.2 m (95% CI, 8.6 to 32.1, P <0.001). Limitations include that most participants were white, the study did not compare semaglutide with other interventions for weight loss, did not assess patients with diabetes or HFrEF, and long-term effects have not been studied.
Bottom line: Semaglutide therapy not only results in significant weight loss but also improves patient-related outcomes in heart failure-related symptoms and physical limitations in patients with HFpEF and obesity.
Citation: Kosiborod MN, Abildstrøm SZ, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389(12):1069-84.
Dr. Cepeda Mora is a hospitalist at Duke University Hospital and a medical instructor in the department of medicine at Duke University School of Medicine in Durham, N.C.