Sitagliptin (Januvia, Glactiv(R), Tesavel(R)) is a dipeptidyl peptidase-4 inhibitor indicated for the treatment of type 2 diabetes mellitus. Oral sitagliptin as monotherapy or combination therapy was generally well tolerated and improved glycaemic control in well designed clinical trials in patients with type 2 diabetes. Glycosylated haemoglobin (HbA(1c)) levels were significantly reduced with sitagliptin monotherapy relative to voglibose monotherapy or placebo, and with sitagliptin as initial combination therapy with metformin or pioglitazone relative to monotherapy with these agents or placebo. Moreover, sitagliptin monotherapy was noninferior to metformin monotherapy in terms of the reduction in HbA(1c) levels. Significant reductions in HbA(1c) levels, relative to background therapy, were also observed with sitagliptin add-on therapy to ongoing treatment with thiazolidinediones, sulfonylureas or insulin with or without metformin, or metformin alone. In terms of the reduction in HbA(1c) levels as add-on treatment to metformin, sitagliptin was noninferior to glipizide and generally did not differ from rosiglitazone, and as add-on treatment to pioglitazone, it did not differ significantly from metformin. Sitagliptin had a low risk of hypoglycaemia (except when used in combination with agents that may be associated with hypoglycaemia, such as sulfonylureas or insulin) and was generally weight-neutral. Although additional comparative data and longer-term studies with glycaemic and clinical outcomes are required to definitively position sitagliptin relative to other antihyperglycaemic agents, current evidence suggests that it is a useful treatment option for patients with type 2 diabetes, with potential advantages including oral administration, a generally weight-neutral effect and a low risk of hypoglycaemia.