Saxagliptin (Onglyza): DPP-4 inhibitor approved for the treatment of type 2 diabetes mellitus

Saxagliptin is an inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme. By inhibiting DPP-4, saxagliptin slows the inactivation of the incretin hormones, which increases their concentrations in the bloodstream and reduces both fasting and postprandial glucose concentrations in a glucose-dependent manner. Saxagliptin was approved on July 31, 2009, for use as monotherapy or as part of combination therapy as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Efficacy. Saxagliptin has been studied as a monotherapy and in combination with metformin, glyburide, and thiazolidinedione therapy. Across 6 double-blind, controlled clinical trials, 4,148 patients were randomized to treatment with saxagliptin as monotherapy, saxagliptin in combination with metformin, saxagliptin in combination with a thiazolidinedione, saxagliptin in combination with glyburide, or placebo. Across the trials, saxagliptin treatment was associated with clinically relevant and statistically significant improvements in hemoglobin A_1c (HbA_1c), fasting plasma glucose, and 2-hour postprandial glucose after a standard oral glucose tolerance test versus placebo. Reductions in HbA_1c were observed across all subgroups (sex, age, race, and baseline body mass index). Saxagliptin was not associated with significant changes in body weight or fasting serum lipid levels compared with placebo.

Safety. A lower dose of insulin secretagogues may be required to reduce the risk of hypoglycemia when these agents are used in combination with saxagliptin. Clinical trials have not definitively established whether saxagliptin affects macrovascular outcomes. The most common adverse events associated with saxagliptin treatment include upper respiratory tract infection, urinary tract infection, headache, and nasopharyngitis.

For more information, go to http://www.onglyza.com.