Semaglutide, a glucagon-like peptide-1 receptor agonist, reduces N-terminal pro-brain natriuretic peptide levels in patients with obesity-related heart failure with preserved ejection fraction, according to a study in the Journal of the American College of Cardiology.

The research, which was a part of the STEP-HFpEF Program, aimed to determine whether the benefits of semaglutide were from weight loss alone or included broader effects on heart failure (HF) pathobiology.

The STEP-HFpEF Program pooled data from 2 double-blind, placebo-controlled, randomized trials involving 1,145 patients with obesity-related HF with preserved ejection fraction (HFpEF). Patients were randomized to receive either semaglutide 2.4 mg or placebo, with the primary outcomes being changes in N-terminal pro-brain natriuretic peptide (NTproBNP), health status (measured by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, KCCQ-CSS), and body weight over 52 weeks.

Results showed that semaglutide reduced NTproBNP levels by 22.19% compared with 4.87% in the placebo group at the 52-week mark (P = 0.0002). The reduction was consistent across various subgroups, suggesting semaglutide's impact on NTproBNP is robust and independent of weight loss.

Furthermore, researchers found that patients with higher baseline NTproBNP experienced more significant improvements in health status and physical limitations compared with those with lower baseline levels, indicating semaglutide may have disease-modifying effects beyond mechanical unloading.

Semaglutide led to substantial weight loss across all baseline NTproBNP levels, with reductions in body weight being consistent regardless of initial NTproBNP levels. This underscores the dual benefit of semaglutide in managing both obesity and HF symptoms.

Funding for the STEP-HFpEF Program was provided by Novo Nordisk. The authors have various disclosures related to consulting fees and research support from pharmaceutical companies, including Novo Nordisk.