In a randomised, controlled trial, semaglutide resulted in greater weight loss, improved symptoms and fewer serious adverse events compared with placebo.

Obesity and type 2 diabetes are common comorbidities in patients with heart failure with preserved ejection fraction (HFpEF). Currently, there are no FDA-approved therapies that specifically treat all three conditions at the same time; however, semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has the potential to do so.

In an industry-funded trial (NCT04916470), investigators randomised 616 adults with HFpEF (left ventricular ejection fraction 45% or greater), body mass index above 30 kg/m² and type 2 diabetes to receive semaglutide (2.4 mg) or matching placebo once weekly for 52 weeks. They assessed dual primary endpoints of change in heart failure symptoms via Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; range, zero to 100, with higher score indicating fewer symptoms) and change in body weight.

The mean change in the KCCQ-CSS was +13.7 points with semaglutide and +6.4 points with placebo, indicating improved symptoms with semaglutide. The mean change in body weight was −9.8% with semaglutide and −3.4% with placebo. Confirmatory secondary end points also favoured semaglutide, including six-minute walk distance, a composite end point (including death, heart failure events and differences in KCCQ-CSS and six-minute walk distance) and C-reactive protein level. Serious adverse events occurred in 18% of patients in the semaglutide group and 29% in the placebo group.

Comment: Semaglutide once again shows clinical benefit. Prior research has shown improved outcomes in patients with diabetes and high cardiovascular risk, in patients with overweight or obesity and high cardiovascular risk, and in patients with HFpEF and obesity but no diabetes. Now, this research shows efficacy in patients with HFpEF, obesity and type 2 diabetes. The many benefits of semaglutide make me very likely to recommend this therapy in appropriate patients for improving symptoms and reducing cardiovascular risk.

KAROL E. WATSON MD, PhD, FACC, John C. Mazziotta, MD, PhD, Term Endowed Chair and Professor of Medicine/Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, USA.

Kosiborod MN, et al. Semaglutide in patients with obesity-related heart failure with preserved ejection fraction and type 2 diabetes. N Engl J Med 2024; 390: 1394-1314.

This summary is taken from the following Journal Watch titles: Cardiology, General Medicine, Ambulatory Medicine, Hospital Medicine.