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Review: Inhibition of dipeptidyl peptidase-4 with vildagliptin: a potential new treatment for type 2 diabetes

Diabetes and Metabolism Translational Medicine Unit, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Vermont College of Medicine, USA, rpratley{at}uvm.edu

Afshin Salsali

Diabetes and Metabolism Translational Medicine Unit, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Vermont College of Medicine, USA

Glenn Matfin

Novo Nordisk Inc. 100 College Road West, Princeton, New Jersey 08540, USA, Division of Endocrinology and Diabetes, Department of Medicine, New York University School of Medicine, New York, New York, USA

Type 2 diabetes mellitus is a growing problem in most parts of the world. There is now good evidence that controlling hyperglycaemia can help prevent many of the serious complications associated with the disease. Despite this evidence and the availability of several classes of oral antidiabetic agents and insulin, many people with diabetes do not achieve adequate glycaemic control (i.e. HbA_1C < 6.5 or 7.0%). Thus, there is an urgent unmet medical need to develop new and better treatments for type 2 diabetes. Among the most promising new classes of drugs for type 2 diabetes are those that leverage the incretin hormone glucagon-like peptide-1 (GLP-1). Vildagliptin, an orally available, potent and specific inhibitor of dipeptidyl peptidase-4 (DPP-4), the enzyme that rapidly inactivates GLP-1, augments endogenous active GLP-1 and gastric inhibitory polypeptide/glucose-dependent insulinotropic polypeptide (GIP) and reduces hyperglycaemia in patients with type 2 diabetes. Studies to date in patients exposed for up to one year indicate that vildagliptin produces clinically significant reductions in HbA_1C when used as monotherapy and in combination with metformin, glimepiride, or insulin. In general, the drug has proved to be well tolerated with low rates of hypoglycaemia and gastrointestinal side effects (including nausea) and no weight gain or oedema.

Key Words: GLP-1 • GIP • incretin hormone • incretin enhancer • DPP-4 • diabetes.

The British Journal of Diabetes & Vascular Disease, Vol. 6, No. 4, 150-156 (2006)
DOI: 10.1177/14746514060060040201


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