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Semaglutide and NT-proBNP in Obesity-Related HFpEF
Quick Takes
- In a prespecified analysis of a randomized controlled trial, use of semaglutide compared with placebo in patients with obesity-associated HFpEF was associated with a decrease in NT-proBNP levels, irrespective of amount of weight lost.
- Semaglutide improved HF symptoms and functional capacity regardless of baseline NT-proBNP levels with few side effects.
Study Questions:
What is the effect of semaglutide compared with placebo on N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels in patients with heart failure and preserved ejection fraction (HFpEF)?
Methods:
This was a prespecified analysis of the randomized controlled STEP-HFpEF program comprised of both patients with obesity-related HFpEF with and without diabetes. Enrolled patients had a left ventricular ejection fraction (LVEF) ≥45% and body mass index ≥30 kg/m2 with New York Heart Association (NYHA) class II-IV symptoms. Patients were randomized to semaglutide 2.4 mg weekly versus placebo.
Results:
A total of 1,145 patients were randomized including 529 without diabetes and 616 with diabetes. NT-proBNP tertiles at baseline were <300 pg/mL, 300-810 pg/mL, and >810 pg/mL. Semaglutide reduced NT-proBNP by week 20 that persisted until week 52 compared to placebo regardless of diabetes status. There was a consistent reduction in NT-proBNP levels with semaglutide compared to placebo regardless of amount of weight lost but participants expecting greater weight loss had lesser reduction in NT-proBNP compared with their baseline levels. Semaglutide improved health status, as measured by Kansas City Cardiomyopathy Questionnaire Clinical Summary Score across all NT-proBNP tertiles with a larger impact on those with higher baseline NT-proBNP. Semaglutide reduced body weight, C-reactive protein, and 6-minute walk distance across all baseline NT-proBNP levels but a larger effect was seen in patients with higher NT-proBNP. Gastrointestinal (GI) side effects were similar across all NT-proBNP levels.
Conclusions:
In a prespecified analysis of a randomized controlled trial, use of semaglutide compared with placebo in patients with obesity-associated HFpEF, was associated with a decrease in NT-proBNP levels, irrespective of amount of weight lost. Semaglutide improved HF symptoms and functional capacity regardless of baseline NT-proBNP levels with few side effects.
Perspective:
Despite extensive improvements in therapies for systolic HF, the search for agents treating diastolic HF remains ongoing. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as semaglutide are rapidly emerging as effective weight loss agents. In this study, semaglutide was associated with a decline in NT-proBNP levels independent of the amount of weight loss. Weight loss associated with placebo did not produce similar changes in NT-proBNP levels, suggesting that the impact of semaglutide extends beyond weight loss. While health status improved regardless of NT-proBNP levels at baseline, the benefit was larger for those with high NT-proBNP levels or more severe HFpEF. It is noteworthy that not all GLP1RAs in HFpEF are associated with a decline in NT-proBNP levels. Furthermore, the medication was well tolerated with low incidence of GI side effects with no cardiac side effects. These data support that semaglutide should be considered in obesity-mediated HFpEF patients.
Clinical Topics: Heart Failure and Cardiac Biomarkers, Prevention
Keywords: Heart Failure, Preserved Ejection Fraction, Natriuretic Peptide, Brain, Obesity
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