Clinical overview of saxagliptin for Type 2 diabetes management

Abstract

Saxagliptin (Onglyza™, Bristol-Myers Squibb, NJ, USA and AstraZeneca, DE, USA) is a potent, orally active, once-daily dipeptidyl peptidase-4 inhibitor that is indicated as an adjunct to diet and exercise alone, or in combination with metformin, a thiazolidinedione or a sulfonylurea to improve glycemic control in adults with Type 2 diabetes mellitus. By inhibiting dipeptidyl peptidase-4, saxagliptin increases concentrations of the intact forms of the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, prolonging their effects. Saxagliptin also improves β-cell function, increases postprandial insulin secretion and reduces postprandial glucagon secretion. Saxagliptin is generally well tolerated with weight-neutral effects and a low incidence of hypoglycemia. Multicenter randomized trials have shown that saxagliptin as monotherapy, as initial therapy with metformin or as add-on therapy with metformin, a sulfonylurea or a thiazolidinedione leads to significant decreases in glycated hemoglobin levels, fasting and postprandial plasma glucose levels and higher percentages of patients attaining target glycated hemoglobin of less than 7% compared with controls.

Keywords::

• dipeptidyl peptidase-4
• DPP-4 inhibitor
• GLP-1
• glucagon-like peptide-1
• glycated hemoglobin
• HbA_1c
• incretin
• metformin
• saxagliptin
• sulfonylurea
• thiazolidinedione
• Type 2 diabetes mellitus

Acknowledgements

The author gratefully acknowledges Drs Roland Chen, David Boulton, Mark Kirby and Mark Donovan for their expertise in critically reviewing the accuracy of the pharmacokinetic/pharmacodynamic, selectivity, and clinical efficacy and safety portions, and providing their approval of the manuscript.

Financial & competing interests disclosure

Julio Rosenstock has served on advisory boards and received honoraria or consulting fees from Pfizer, Roche, Sanofi-Aventis, Novo Nordisk, Eli Lilly, MannKind, GlaxoSmithKline, Takeda, Daiichi Sankyo, Forest, Johnson & Johnson, Novartis, Boehringer Ingelheim and Amylin. He has received research grants from Merck, Pfizer, Sanofi-Aventis, Novo Nordisk, Roche, Bristol-Myers Squibb, Eli Lilly, Forest, GlaxoSmithKline, Takeda, Novartis, AstraZeneca, Amylin, Johnson & Johnson, Daiichi Sankyo, MannKind and Boehringer Ingelheim. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Technical and editorial assistance were provided by Gina Coviello, MS, Quintiles Medical Communications, Parsippany, NJ, USA.