The Role of Glucagon in the Pathophysiology and Treatment of Type 2 Diabetes

Abstract Type2 diabetes is a disease involving both inadequate insulin levels and increased glucagonlevels. While glucagonand insulin work together to achieve optimal plasma glucose concentrations in healthy individuals, the usual regulatory balance between these 2 critical pancreatic hormonesis awry in patients with diabetes. Although clinical discussion often focuses on the role of insulin, glucagonis equally important in understanding type 2 diabetes. Furthermore, an awareness of the role of glucagonis essential to appreciate differences in the mechanismsof actionof various classes of glucose-lowering therapies. Newer drug classessuch as dipeptidyl peptidase-4 inhibitorsand glucagon-like peptide-1 receptoragonists improve glycemic control, in part, by affecting glucagonlevels. This review provides an overview of the effect of glucose-lowering therapies on glucagonon the basis of an extensive PubMed literature search to identify clinical studies of glucose-lowering therapies in type 2 diabetes that included assessment of glucagon. Clinical practice currently benefits from available therapies that impact the glucagonregulatory pathway. As clinicians look to the future, improved treatment strategies are likely to emerge that will either use currently available therapies whose mechanismsof actioncomplement each other or take advantage of new therapies based on an improved understanding of glucagonpathophysiology.