peer reviewed ; Sitagliptin (Januvia) is the first selective antagonist of dipeptidylpeptidase-4, an enzyme that degrades glucagon-like peptide-1 (GLP-1). This hormone is mainly secreted by ileal L cells and this secretion is abnormally low in patients with type 2 diabetes. Sitagliptin increases post-meal insulin secretion ("incretin effect) by enhancing the postprandial GLP-1 response ("incretin enhancer"), in a glucose-dependent manner. It improves glycaemic control (HbA1c) in type 2 diabetic patients treated by diet alone, by metformin, by sulfonylurea, by glitazone or by a metformin-sufonylurea combined therapy. The glucose-lowering effect is similar to that of glipizide, but with the advantage of no weight gain and no hypoglycaemic episodes. The tolerance to sitagliptin is excellent. Treatment is simple, with 100 mg once daily, without need of titration or home blood glucose monitoring. In Belgium, sitagliptin is currently reimbursed in patients with type 2 diabetes not adequately controlled with diet and metformin monotherapy.