GIPR and obesity due to melanocortin 4 receptor deficiency: While early studies demonstrated the clinical potential of GIPRA in rodent models of type 2 diabetes/obesity [107, 108], development of GIP agonists for human use was largely curtailed by GIPR downregulation, the lack of glycemic benefit of GIPRA, as well as the concept that GIPR agonism drives obesity [109].