Gliptins: DPP-4 inhibitors to treat type 2 diabetes

Gliptins represent an emerging new class of oral agents to treat type 2 diabetes. They act by inhibiting the enzyme dipeptidyl peptidase-4 (DPP-4). This enzyme inactivates the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These hormones are released from the intestine during a meal and act on the pancreas to increase nutrient-stimulated insulin secretion. Thus DPP-4 inhibitors serve as incretin enhancers; they delay inactivation of GLP-1 and GIP, increasing the insulin response to a meal, which improves glycaemic control. This therapeutic approach carries a low risk of interprandial hypoglycaemia and does not cause weight gain. 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 metformin or a thiazolidinedione. Other gliptins, notably vildagliptin (Galvus), saxagliptin and alogliptin are advanced in clinical development. Copyright © 2007 John Wiley & Sons, Ltd.