Sitagliptin is an orally administered, potent, and highly selective inhibitor of dipeptidyl peptidase-4 (DPP-4) and was the first agent of its class to be approved for use in the management of adults with type 2 diabetes. Numerous randomized placebo- or active comparator-controlled trials have demonstrated the efficacy of sitagliptin in terms of improving glycaemic control in patients with type 2 diabetes, including its use as monotherapy, initial combination therapy (usually with fixed-dose combinations ofsitagliptin/metformin), or add-on therapy to metformin or other antihyperglycaemic drugs, with or without metformin. Sitagliptin was generally well tolerated in clinical trials, had a low risk of hypoglycemia (although this depends on background therapy), and had a neutral effect on body weight.It stimulates insulin secretion when hyperglycemia is present and inhibits glucagon secretion. In clinical studies, it is weight neutral. This article gives an overview of the mechanism of action, the pharmacology, and the clinical efficacy and safety of sitagliptin in type 2 diabetes therapy.