Saxagliptin for type 2 diabetes

Abstract

Saxagliptin (Onglyza™) is a potent, selective, once-daily dipeptidyl peptidase-4 (DPP-4) inhibitor indicated for improving glycemic control in patients with type 2 diabetes (T2D). By blocking DPP-4, saxagliptin increases and prolongs the effects of incretins, a group of peptide hormones released by intestinal cells after meals, which stimulate glucose-dependent insulin secretion to lower blood glucose. In controlled clinical trials, saxagliptin administered as monotherapy or in combination with metformin, glyburide, or a thiazolidinedione improved glycemic control in a clinically significant manner, reflected by significant decreases in glycated hemoglobin (monotherapy, −0.5%; add-on to metformin, thiazolidinedione, or sulfonylurea, −0.6% to 0.9%; initial combination with metformin, −2.5%), fasting plasma glucose, and postprandial glucose compared with controls. Additionally, saxagliptin improved β-cell function, reflected as increases in homeostasis model assessment (HOMA)-2β. Saxagliptin was generally well tolerated; it did not increase hypoglycemia compared with controls, and was weight neutral. A meta-analysis of Phase II and III trials showed that saxagliptin did not increase the risk of major cardiovascular events. Professional organizations have updated their guidelines for T2D to include a DPP-4 inhibitor as an early treatment option—either as initial therapy in combination with metformin, or as add-on therapy for patients whose glycemia is inadequately controlled by a single oral antidiabetic drug.

Keywords:

• saxagliptin
• dipeptidyl peptidase-4 (DPP-4) inhibitor
• type 2 diabetes

Disclosure

Dr Antonio R Chacra has received research grants from Eli Lilly, MSD, Novartis, Novo Nordisk, Bristol-Myers Squibb, AstraZeneca, and sanofi-aventis. He is a member of the Brazilian Bristol-Myers Squibb/AstraZeneca Saxagliptin Board and has received honorarium fees for lecturing on saxagliptin. Technical and editorial assistance was provided by Gina Coviello, MS, Quintiles Medical Communications, Parsippany, NJ, USA.