Glucagon-related advancements in diabetes therapy

Abstract

Traditionally, treatment for type 2 diabetes (T2D) centered on the failure of insulin secretion from the beta cells of the pancreas and insulin resistance. Though effective in certain respects, these treatments are marred by multiple undesirable side effects. The discovery of the incretin defect and the role of glucagon in T2D shifted the focus to therapies that addressed not only the beta cell defect but also the alpha cell defect in the pancreas. Therapies addressing these defects, simultaneously, have switched the entire focus of T2D therapy by not only improving glycemic control but also reducing the risk of hypoglycemia and weight gain and improving outcomes. These newer modalities of treatment started off with dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists (GLP1-RAs), and now further treatments in the form of twincretins (GLP1/GIP dual agonists) and triple agonists (GLP1/GIP/glucagon agonists) are unraveling. This article provides a summary of the evidence available with these newer antidiabetics, which address the glucagon defect in T2D.