Clinical Effectiveness and Safety of Oral Semaglutide in a Real-World Cohort of Patients with Heart Failure with Reduced Ejection Fraction, Type 2 Diabetes and Obesity: A Propensity Score-Matched Analysis

Bacground/Objectives: There is limited evidence on the role of glucagon-like peptide-1 receptor agonists in heart failure. We aimed to analyze the clinical efficacy of oral semaglutide in terms of health status and change in body weight in patients with heart failure with reduced ejection fraction, type 2 diabetes, and obesity. Methods: This observational, retrospective, real-world study included patients treated with oral semaglutide (Oral-Sema Group) and without glucagon-like peptide-1 receptor agonists (Control Group). The primary outcome was heart failure status, defined as a ≥5 point difference in the Kansas City Cardiomyopathy Questionnaire total symptom score, and change in body weight at 24 months. Results: After 1:1 propensity score matching, 162 patients were included in each group (mean age 71.0 years, mean body mass index 32.1, 52.9% females). Patients in the Oral-Sema Group were more likely to have improvement in heart failure health status from baseline to 24 months (OR: 2.45; 95%CI: 1.25–3.65; p = 0.012). The mean change in body weight was −8.0 ± 2.1 kg in patients with oral semaglutide and −1.9 ± 1.0 kg in control patients (p < 0.01). After treatment, there were negative correlations between the Kansas City Cardiomyopathy Questionnaire total symptom score and body weight (r = −0.558, p < 0.01) and glycated hemoglobin (r = −0.491, p = 0.017). It had good tolerability and safety. Conclusions: Oral semaglutide was associated with an improvement in heart failure health status and weight loss in patients with heart failure with reduced ejection fraction, type 2 diabetes, and obesity. Further research on glucagon-like peptide-1 receptor agonists in heart failure with reduced ejection fraction is needed.