Incretin-based treatments have emerged as new modalities for the treatment of type 2 diabetes mellitus (T2DM). In contrast to current
antidiabetic treatments, these agents target both insulin insufficiency and inappropriate hyperglucagonemia*two major components of type
2 diabetic pathophysiology*both known to contribute significantly to the hyperglycemic state of patients with T2DM. This article outlines the
role of hyperglucagonemia in type 2 diabetic pathophysiology, summarizes the physiologic effects of glucagon-like peptide-1 (GLP-1), and
gives an introduction to incretin-based treatments with emphasis on their glucagon-lowering effects. Finally, we review available glucagon
data from current clinical studies on incretin-based treatment modalities (dipeptidyl peptidase 4 [DPP4] inhibitors and GLP-1 receptor
agonists). Most of these studies suggest that both DPP4 inhibitors and GLP-1 receptor agonists lower fasting and postprandial plasma
glucagon, and recent data suggest that these effects contribute importantly to the glucose-lowering effect of these treatments.