Saxagliptin : a new DPP-4 inhibitor for the treatment of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic with increasing impact on individuals and healthcare providers. Available treatments (such as metformin, sulfonylureas, glitazones, and insulin) have proven unsatisfactory in producing a long-lasting impact on glycemic control. In addition, most of these treatments have undesirable side effects such as weight gain and hypoglycemia. As a result, exploring new treatment targets and new therapies is mandatory in order to treat this condition. The incretin pathway, in particular glucagon-like peptide (GLP-1), plays an important pathological role in the development of T2DM, and treatments targeting the incretin system have recently become available. These can mainly be divided into two broad categories; GLP-1 agonists/analogs (exenatide, liraglutide), and dipeptidyl peptidase-4 (DPP-4; the enzyme responsible for rapid inactivation of incretins) inhibitors (sitagliptin, vildagliptin). Saxagliptin is a novel DPP-4 inhibitor that has recently completed phase 3 studies. Saxagliptin is a potent and specific inhibitor of DPP-4 (in comparison with other dipeptidyl peptidase enzymes) that is given once daily. Current data suggest that saxagliptin as monotherapy or in combination with metformin, glyburide, or a glitazone results in significant reductions in fasting and postprandial plasma glucose and hemoglobin A 1c (HbA1c). Saxagliptin is well tolerated and does not increase hypoglycemia compared with the placebo, and is probably weight neutral. Saxagliptin will be a new effective drug in the currently available variety of antidiabetic medications for patients with T2DM.