As part of our efforts in developing long-acting therapies for chronic diseases, we have previously utilized the in-house developed polyethylene glycol (PEG)-fatty acid stapling technology to produce ”E6”, a potent, long-acting GLP-1R agonist exhibiting excellent efficacy in animal models of diabetes and obesity [7]. Here, GLP1R is linked to obesity due to melanocortin 4 receptor deficiency.