Obesity is quite common in patients suffering from heart failure with preserved ejection fraction (HFpEF).¹ Semaglutide is a glucagon-like peptide-1 receptor agonist that has been shown to cause weight loss and reduce cardiovascular events in patients with obesity.¹ Whether it can be used safely and lead to clinical improvements in patients with HFpEF is unknown.

Semaglutide Treatment Effect in People With Obesity and HFpEF (STEP-HFpEF) was a randomized control, double blinded study that assessed once weekly semaglutide in patients with HFpEF (left ventricular ejection fraction [LVEF] ≥45%) and a body mass index (BMI) ≥30 kg/m2 with New York Heart Association (NYHA) class II-IV symptoms.¹ In this study, 529 patients were randomized in a 1:1 fashion between semaglutide and placebo.¹ The majority of the patients were white (96%) and female (56%) in both groups, with a median age of 69 years.¹ Subjects were initiated on semaglutide 0.25 mg and were titrated every 4 weeks to a maximum dose of 2.4 mg.¹ The co-primary outcomes were to assess changes in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at 52 weeks, as well as change in body weight.¹

Investigators reported a significant improvement in KCCQ-CSS (16.6 vs. 8.7; p <0.001) as well as significant reduction in BMI (-13.3 vs. -2.6; p <0.001) in patients receiving semaglutide versus placebo.¹ Secondary outcomes that demonstrated benefit of semaglutide included significant reduction in C-reactive protein and increase in 6 minute walk distance.¹ Both adverse events and discontinuation of study medication were similar between the two groups.¹

In summary, semaglutide showed significant reduction in body weight and improvement in HF symptoms in patients with HFpEF and obesity. One limitation is that very few patients were prescribed sodium-glucose cotransporter-2 inhibitors at the time of the trial, which are now standard of care in HFpEF. Future trials will need to determine if semaglutide can reduce HF hospitalizations and cardiovascular mortality in these patients.

References

1. Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al.; STEP-HFpEF Trial Committees and Investigators. Semaglutide in patients with heart failure With preserved ejection fraction and obesity. N Engl J Med 2023;389:1069-84.