Tirzepatide, a dual agonist of GLP-1 and GIP receptors, is the most advanced compound in its class: in the SUMMIT trial, among patients with HFpEF and obesity or type 2 diabetes, it lowered the risk of HF-related adverse events and cardiovascular death [19]; in the SURMOUNT-5 trial, it outperformed semaglutide in reducing body weight and waist circumference at week 72 in participants with obesity but without diabetes, reinforcing its cardiometabolic potential [98]. Here, GLP1R is linked to obesity due to melanocortin 4 receptor deficiency.