Extrapancreatic contribution to glucose regulation by dipeptidyl peptidase 4 inhibition

Dipeptidyl peptidase 4 (DPP-4) inhibitors are now being clinically utilized as glucose-lowering medications for the treatment of type 2 diabetes. Their widespread use and effective glucose-lowering properties have led to great interest in the mechanism of action of this class of drug. Although it has been well accepted that DPP-4 inhibitors lower glucose in part by increasing postprandial insulin secretion and suppressing fasting and postprandial hyperglucagonemia, recent studies have suggested that DPP-4 inhibition has other metabolically beneficial properties that are extrapancreatic in nature. This review explores the changes in DPP-4 expression and activity in metabolic disease states and discusses the metabolic consequences of DPP-4 inhibition on a systemic and tissue-specific basis. It concludes that there is considerable scientific evidence and a growing body of clinical evidence to suggest that DPP-4 inhibition would be beneficial in a number of metabolic disorders in addition to type 2 diabetes.