NCT06541509RECRUITINGPhase 1Phase 2Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, primarily used for treatment of type-2 diabetes mellitus. GLP-1 receptors are present on pancreatic islet β-cells, δ-cells and α-cells. Their stimulation increases insulin and somatostatin secretion, and decreases glucagon secretion. In addition, GLP-1 receptor agonists appear to have multiple extrapancreatic actions, which remain poorly defined. In large clinical trials, semaglutide improved the outcomes in obese patients, patients with heart failure with preserved ejection fraction, and decreased the heart failure hospitalizations in patients with type 2 diabetes. The aim of the present study is to investigate the underlying mechanisms of the beneficial clinical effects of semaglutide in the setting of chronic heart failure.
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Inclusion Criteria: * Age: 20-80 years * Presence of heart failure * Body-mass index 27 kg/m2 or greater * Stable optimally tolerated dosages of heart failure therapies for 3 months * N-terminal pro B-type natriuretic peptide levels \>350 pg/mL Exclusion Criteria: * Presence of type 1 or type 2 diabetes or glycated haemoglobin higher than 6.5% * Pregnancy or potential to become pregnant * Cancer * Liver dysfunction (aspartate aminotransferase and/or alanine aminotransferase \> 3 times upper limits of normal or total bilirubin greater than 1.5 times upper limits of normal) * Renal dysfunction (estimated glomerular filtration rate less than 25 mL/min/1.73 m2) * Hospitalization in the past 3 months for reasons other than heart failure * New York Heart Association (NYHA) functional class I or functional class IV symptoms. * Prior or planned bariatric surgery * Self-reported change in body weight \>11 lbs (5 kg) within 3 months before enrollment * Acute or chronic infection