Gliptins - The Novel Players in Glucose Homeostasis.

ABSTRACT

Type 2 diabetes mellitus is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. Tight glycemic control is considered to be important in the therapy of type 2 diabetes mellitus, but treatment with a single agent is not sufficient to achieve this for the majority of patients. So, there is a need for new antidiabetic agents with favorable side effect profiles to use in combination therapy. The gliptins, an emerging new class of oral drugs for type 2 diabetes mellitus, lower blood glucose levels by a novel mechanism of inhibiting the enzyme dipeptidyl peptidase-4 (DPP-4) that inactivates incretin, released from the intestine following a meal to increase pancreatic insulin secretion. Gliptins enhance the circulating levels of incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) and improve glycemic control. This therapeutic approach carries a low-risk of interprandial hypoglycemia, does not cause weight gain and is well-tolerated. The first gliptin, sitagliptin (Januvia), was introduced in the UK in April 2007 as add-on therapy for patients with type 2 diabetes inadequately controlled with oral hypoglycemic agents. Other gliptins, notably vildagliptin (Galvus), saxagliptin and melogliptin are advanced in clinical development. This article reviews the current evidence on the effectiveness of gliptins and suggests several ways in which these agents could be used in diabetes treatment.