Semaglutide effective in improving symptoms in obese heart failure patients, NEJM study

Semaglutide, a glucagon-like peptide 1 (GLP-1) agonist is the latest entry in the arena of medications combating heart failure with preserved ejection fraction. According to the results of recently published STEP-HFpEF trial, treatment with semaglutide (2.4 mg) led to larger reductions in symptoms and physical limitations, greater improvements in exercise function, and greater weight loss than placebo in obese patients suffering from HFpEF. The results were recently published in NEJM.

In the past, interventions that showed benefits for patients with heart failure with reduced ejection fraction were not shown to be effective for treating heart failure with preserved ejection fraction.

Current concepts that have been used to explain the discrepancy note that multiple coexisting conditions define both symptoms and outcomes in heart failure with preserved ejection fraction, since patients with this form of heart failure tend to be older and to have more accompanying metabolic disease.

Hence the concept that HFpEF is a metabolic entity rather than an isolated cardiac disease, gave birth to the idea of using metabolic modifiers like semaglutide for this entity.

The authors randomly assigned 529 patients who had HFpEF and a BMI >/= 30 to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The dual primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score and the change in body weight.

Authors Kosiborod et al. found that patients in the treatment arm had more weight loss (13.3% loss vs. 2.6% in the placebo group) and significantly improved the Kansas City Cardiomyopathy Questionnaire clinical summary score and the 6-minute walk distance.

In addition, semaglutide increased the 6-minute walk distance, resulted in more wins in the evaluation of the hierarchical composite end point (that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance), and reduced CRP levels to a greater extent than placebo.

The encouraging findings for semaglutide in patients with heart failure with preserved ejection fraction reported here potentially add a much-needed extra option for these patients and provide another upstream treatment for patients with signs of this condition plus a high BMI.

Source: NEJM: DOI: 10.1056/NEJMoa2306963