Given the well-established therapeutic role of GLP-1 RAs in managing T2DM and/or overweight/obesity, and their close interrelationship with HFpEF, scientific focus has shifted to investigating the role of GLP-1 RAs in obesity-related HFpEF, regardless of T2DM status. Here, GLP1R is linked to obesity due to melanocortin 4 receptor deficiency.