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International Journal of Endocrinology
Volume 2013, Article ID 686315, 10 pages
http://dx.doi.org/10.1155/2013/686315
Review Article

Pharmacogenetics of Oral Antidiabetic Drugs

1Department of Epidemiology, Erasmus MC, 3015 CE Rotterdam, The Netherlands
2Pharmacy Foundation of Haarlem Hospitals, 2035 RC Haarlem, The Netherlands
3Medical Research Institute, University of Dundee, Dundee DD1 9SY, UK
4Department of Internal Medicine 4, Faculty of Medicine, P. J. Šafárik University, 041 80 Košice, Slovakia
5Department of Internal Medicine 4, L. Pasteur University Hospital, Rastislavova 43, 041 90 Košice, Slovakia

Received 15 February 2013; Revised 28 October 2013; Accepted 28 October 2013

Academic Editor: Khalid Hussain

Copyright © 2013 Matthijs L. Becker et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Oral antidiabetic drugs (OADs) are used for more than a half-century in the treatment of type 2 diabetes. Only in the last five years, intensive research has been conducted in the pharmacogenetics of these drugs based mainly on the retrospective register studies, but only a handful of associations detected in these studies were replicated. The gene variants in CYP2C9, ABCC8/KCNJ11, and TCF7L2 were associated with the effect of sulfonylureas. CYP2C9 encodes sulfonylurea metabolizing cytochrome P450 isoenzyme 2C9, ABCC8 and KCNJ11 genes encode proteins constituting ATP-sensitive K+ channel which is a therapeutic target for sulfonylureas, and TCF7L2 is a gene with the strongest association with type 2 diabetes. SLC22A1, SLC47A1, and ATM gene variants were repeatedly associated with the response to metformin. SLC22A1 and SLC47A1 encode metformin transporters OCT1 and MATE1, respectively. The function of a gene variant near ATM gene identified by a genome-wide association study is not elucidated so far. The first variant associated with the response to gliptins is a polymorphism in the proximity of CTRB1/2 gene which encodes chymotrypsinogen. Establishment of diabetes pharmacogenetics consortia and reduction in costs of genomics might lead to some significant clinical breakthroughs in this field in a near future.