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

Jun 15, 2025European journal of internal medicine

Effectiveness and safety of once-daily oral semaglutide in patients with heart failure, type 2 diabetes, and obesity in everyday care

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Abstract

Patients treated with once-daily oral semaglutide experienced a mean weight loss of -9.5 ± 3.2 kg over 18 months.

Patients taking semaglutide were more likely to show an improvement in heart failure health status compared to those not taking it.
The odds of improvement in heart failure health status were approximately 2.92 times greater for the semaglutide group.
There was a significant negative correlation between heart failure symptoms and body weight, suggesting that higher weight is associated with worse symptoms.
A negative correlation was also observed between heart failure symptoms and glycated hemoglobin levels.
The treatment was reported to have good tolerability and safety.

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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.

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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

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