The glucagon receptor belongs to the class B GPCR and plays a critical role in the maintenance of glucose homeostasis.367,368 Given the key role of glucagon in elevating glycemia, small-molecule antagonists targeting GCGR are considered promising treatments for diabetes.369–371 In support of this concept, a novel allosteric antagonist targeting GCGR, MK-0893 (Fig. 32), has advanced into phase 2 clinical studies to treat type 2 diabetes mellitus;372 however, side effects, including increased LDL-C, have hindered its clinical use.373. Here, GCG is linked to type 2 diabetes mellitus.