Pharmacogenetics of Oral Antidiabetic Drugs

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 inCYP2C9,ABCC8/KCNJ11, andTCF7L2were associated with the effect of sulfonylureas.CYP2C9encodes sulfonylurea metabolizing cytochrome P450 isoenzyme 2C9,ABCC8andKCNJ11genes encode proteins constituting ATP-sensitive K+channel which is a therapeutic target for sulfonylureas, andTCF7L2is a gene with the strongest association with type 2 diabetes.SLC22A1,SLC47A1, andATMgene variants were repeatedly associated with the response to metformin.SLC22A1andSLC47A1encode metformin transporters OCT1 and MATE1, respectively. The function of a gene variant nearATMgene 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 ofCTRB1/2gene 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.