OBJECTIVE To review the pharmacology, pharmacokinetics, efficacy, and safety of saxagliptin, a new dipeptidyl peptidase-4 (DPP-4) inhibitor for the treatment of type 2 diabetes. METHODS Searches of PubMed (1966-March 2010) and International Pharmacy Abstracts (1970-March 2010) were conducted using the key words saxagliptin, Onglyza, and BMS-477118. A review of bibliographies of retrieved articles was also performed to identify additional references. METHODS All identified studies published in English and involving efficacy and safety of saxagliptin in the treatment of type 2 diabetes were reviewed. RESULTS Saxagliptin is a competitive inhibitor of DPP-4 that slows the degradation of incretin hormones, thereby stimulating insulin secretion, reducing postprandial glucagon, and decreasing glucose levels. Saxagliptin is well absorbed after oral administration and demonstrates a pharmacokinetic profile that is compatible with once-daily dosing. Clinical trials with saxagliptin monotherapy for the treatment of type 2 diabetes showed a reduction in hemoglobin A(1c) (A1C) of 0.43-0.9%. Saxagliptin has demonstrated similar reductions in A1C when used as add-on therapy with metformin, sulfonylureas, and thiazolidinediones. The combination of saxagliptin and metformin for initial therapy in treatment-naïve patients was associated with greater improvements in A1C than either agent alone. In general, saxagliptin therapy is well tolerated. The most common adverse effects occurring in clinical trials were headache, nasopharyngitis, upper respiratory tract infections, and urinary tract infections. CONCLUSIONS Saxagliptin is effective as monotherapy or add-on therapy for the management of type 2 diabetes. Because saxagliptin has a higher cost and reduces A1C and other surrogate markers of glucose control to a lesser extent than other well-validated therapies, such as metformin, saxagliptin should be reserved for patients who fail or are intolerant of conventional treatments for type 2 diabetes.