Pharmacogenetics of Oral Antidiabetic Drugs

Abstract EN

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.