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. 2025 Sep:139:106378.
doi: 10.1016/j.ejim.2025.06.007. Epub 2025 Jun 14.

Efficacy and safety of once-daily oral semaglutide in patients with heart failure with preserved ejection fraction, type 2 diabetes and obesity: a real-world study

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Efficacy and safety of once-daily oral semaglutide in patients with heart failure with preserved ejection fraction, type 2 diabetes and obesity: a real-world study

Alicia Trenas et al. Eur J Intern Med. 2025 Sep.

Abstract

Background: There is limited evidence on the role of glucagon-like peptide-1 receptor agonists in heart failure. This work analyzes the efficacy of once-daily oral semaglutide in terms of health status and change in body weight in patients with heart failure with preserved ejection fraction, type 2 diabetes, and obesity.

Methods: This prospective, real-world study included patients treated with once-daily semaglutide (O-Sema Group) and without glucagon-like peptide-1 receptor agonists (Control Group). The primary outcome was the heart failure status, defined as the ≥5 point difference in the Kansas City Cardiomyopathy Questionnaire total symptom score, and change in body weight at 18 months.

Results: After a 1:1 propensity score matching, 202 patients were included in each group (mean age 77.8 years, mean body mass index 33.5, 59.2 % females). Patients in the O-Sema Group were more likely to have an improvement in heart failure health status from baseline to 18 months (OR:2.92; 95 %CI: 1.45-4.90; p < 0.01). The mean change in body weight was -9.5 ± 3.2 kg in patients with oral semaglutide and -2.0 ± 1.1 kg in control patients (p < 0.01). After treatment, there were negative correlations between the Kansas City Cardiomyopathy Questionnaire total symptom score and the body weight (r=-0.577, p < 0.01) and glycated hemoglobin (r=-0.499, p = 0.011). It had good tolerability and safety.

Conclusions: Once-daily oral semaglutide was associated with an improvement in heart failure health status, and weight loss in patients with heart failure with preserved ejection fraction, type 2 diabetes, and obesity. Further research on glucagon-like peptide-1 receptor agonists in heart failure with preserved ejection fraction is needed.

Keywords: Heart failure; Obesity; Preserved left ventricular ejection fraction; Semaglutide; Type 2 diabetes.

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Conflict of interest statement

Declaration of competing interest The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.

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