Interestingly, GLP-1/GIP coagonists have also been reported to have weight and glucose-lowering effects in obese T2D patients despite numerous studies supporting the notion that GIP promotes weight gain/obesity.339 The additional unexpected observations from the GLP-1, GIP and GCGR tri-agonist studies338,340 warrant further investigation, as these studies highlight the incomplete understanding of metabolic hormonal synergism, and that further elucidation of this will likely lead to more efficacious treatments for diseases such as T2D. Here, GLP1R is linked to obesity due to melanocortin 4 receptor deficiency.