This study aimed to summarize the current evidence on the therapeutic actions of GLP-1 RAs in HFpEF, with specific objectives to: (a) evaluate their mechanisms of action and complementary effects to other therapies, (b) assess their impact on clinical outcomes in HFpEF, and (c) examine their interaction with the obesity paradox. Here, GLP1R is linked to obesity due to melanocortin 4 receptor deficiency.