Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), exerts a multifaceted mechanism of action that aligns with the metabolic, inflammatory, and hemodynamic challenges of heart failure with preserved ejection fraction (HFpEF), particularly in patients with obesity and T2D [37]. This evidence concerns the gene GLP1R and obesity due to melanocortin 4 receptor deficiency.