The pathophysiologic role of incretins

Abstract

Many patients with type 2 diabetes mellitus (T2DM) are unable to achieve adequate glycemic control. Of the approximately 19 million individuals with T2DM in the United States, only about a third achieve the hemoglobin A(1c) (HbA(1c)0 goal set forth by the American Diabetes Association (HbA(1c) <7% [6% if it can be achieved safely]). The incretin mimetics are a new class of medications available for treating patients with T2DM. They mimic the action of incretins, which are peptide hormones that originate in the gastrointestinal tract. The two major incretins in humans are glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). These hormones are released during nutrient absorption, augmenting insulin secretion. However, incretins are susceptible to degradation by dipeptidyl peptidase IV (DPP-IV). Dipeptidyl peptidase IV inhibitors suppress the degradation of incretins, thus extending the activity of GLP-1 and GIP. The glycemic profiles of patients after administration of incretin mimetics and DPP-IV inhibitors show improvement in postprandial glucose levels and ultimately in HbA(1c). Therefore, incretin mimetics and DPP-IV inhibitors may play a clinically significant role in the treatment of patients with T2DM.