Saxagliptin: A dipeptidyl peptidase-4 inhibitor in the treatment of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by insulin deficiency or resistance. Management starts with single oral antidiabetic drug (OAD) but eventually switch over to combination therapy because of progressive β-cell dysfunction. Hypoglycemia, weight gain, and adverse cardiovascular events are major limitations of the available OADs (Sulfonylureas [SUs], thiazolidinediones [TZDs]). Saxagliptin, a reversible, competitive dipeptidyl peptidase-4 inhibitor, is recently approved agent in the treatment of T2DM. It acts by preventing the degradation of glucagon-like peptide – 1 and hence increases secretion of insulin and decreases secretion of glucagon. It is a well-tolerated agent with commonly reported adverse events which include upper respiratory tract infection, urinary tract infection, and headache. Hypoglycemia, weight gain, and adverse cardiovascular events are negligible as compared with other OADs. In clinical studies, saxagliptin was found to be effective and well tolerated when used as a monotherapy as well as in combination with metformin, SUs and TZDs. It is administered in the dose range of 2.5 to 5 mg once a day regardless of meal. Dosage reduction is required in patients having moderate to severe renal impairment as well as with concurrent administration of strong CYP3A4/5 inhibitors. To conclude, saxagliptin because of its novel mechanism of action (preserving beta cell function) and better tolerability profile seems to be a promising agent in the treatment of T2DM, especially in the early stage of the disease, but long-term clinical studies are required to prove its status in the management of T2DM.