Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

medwireNews: Weekly treatment with semaglutide reduces heart failure symptoms, physical limitations, and body weight, relative to placebo, among people with obesity-related heart failure with preserved ejection fraction and type 2 diabetes, study findings indicate. Mikhail Kosiborod and co-investigators (Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, USA) say their data “extend the broad clinical benefits of semaglutide and safety findings to persons with heart failure with preserved ejection fraction and type 2 diabetes.” The STEP-HFpEF DM trial included 616 patients (median age 69 years, 56% men) who had heart failure with preserved ejection fraction, a BMI of at least 30.0 kg/m2 (median 36.9 kg/m2), and type 2 diabetes. They were randomly assigned to receive once-weekly semaglutide 2.4 mg (n=310) or placebo (n=306) for 52 weeks. At baseline, participants had a median Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) of 59.4 points. The researchers explain that the KCCQ-CSS measures self-reported heart failure-related symptoms and physical function. Scores range from 0 to 100, with higher scores reflecting better health status. After 52 weeks of treatment, the KCCQ-CSS increased by a mean 13.7 points among patients given semaglutide and by 6.4 points among those given placebo, a significant 7.3-point difference between the groups. In addition, body weight fell by a significantly greater degree during semaglutide treatment than during placebo use, at average reductions of 9.8% and 3.4%, respectively, from a baseline median of 102.7 kg. Kosiborod and colleagues note that semaglutide-associated weight loss in the current study was approximately 40% lower than that observed in the earlier STEP-HFpEF trial, which excluded patients with diabetes. They say this “suggests that the mechanisms of benefit with semaglutide may extend beyond weight loss and may include direct effects on decongestion; vascular, skeletal muscle, and mitochondrial function; epicardial adipose tissue; inflammation; and insulin resistance, factors that (unlike weight loss) may be more pronounced in patients with type 2 diabetes than in those without type 2 diabetes.” Secondary endpoints, including 6-minute walk distance and C-reactive protein (CRP) level, also favored semaglutide over placebo. Specifically, 6-minute walk distance increased by an average of 12.7 m at week 52 relative to the baseline median of 280 m among people in the semaglutide group, whereas those in the placebo group recorded a mean decrease of 1.6 m. For CRP, participants in the semaglutide group had a 42.0% reduction in the CRP level at 52 weeks versus a 12.8% reduction with placebo. Median baseline levels were 3.7 mg/L and 3.3 mg/L, respectively. Baseline glycated hemoglobin (HbA1c) was a median of 6.7% (49.7 mmol/mol) in the semaglutide arm and 6.9% (51.9 mmol/mol) in the placebo arm. At 52 weeks, HbA1c had decreased by a mean 0.7 percentage points in the intervention group but increased by 0.1 percentage points in the control group. The risk for hospitalization or an urgent visit for intravenous treatment for heart failure was a significant 60% lower among participants receiving semaglutide versus placebo, occurring at rates of 2.3% and 5.9%, respectively. The researchers comment: “Despite the relatively small number of [heart failure] events, they were distributed favorably to semaglutide as compared with placebo, which occurred in parallel with substantial reductions in [N-terminal pro–B-type natriuretic peptide] levels, a finding that offers further support for similar observations in the STEP- HFpEF trial and suggests important disease-modifying effects of semaglutide.” They continue: “Collectively, these results provide a signal for a potential reduction in clinical events, which requires further confirmation in heart failure outcome trials.” Kosiborod and team also carried out a safety analysis and found that serious adverse events occurred at a significantly lower rate among the people given semaglutide compared with those given placebo (17.7 vs 28.8%). Discontinuations due to any grade of adverse events occurred in 10.6% and 8.2%, respectively. The study findings are published in The New England Journal of Medicine and were simultaneously presented at the American College of Cardiology Scientific Sessions 2024 in Atlanta, Georgia, USA. medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group N Engl J Med 2024; doi:10.1056/NEJMoa2313917 ACC 2024; Atlanta, Georgia, USA: 6–8 April

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