The role of pharmacogenetics in drug disposition and response of oral glucose-lowering drugs

Abstract

The primary goal of type 2 diabetes mellitus (T2DM) disease management is improvement of quality of life and prevention of complications. One way to achieve these goals is improving glycemic control by using different types of oral glucose-lowering medications. Currently seven different pharmacological oral glucose-lowering drug classes are available, each with its own mechanism of action and characteristics regarding absorption, distribution, metabolism, and elimination. Unfortunately, the response to the different types of glucose-lowering medication is highly variable between individuals resulting in unnecessary treatment failure. Genetic factors are thought to contribute to the variability in response and may present an opportunity to improve treatment outcome. In recent years, many efforts were taken to identify genetic variants that influence the pharmacokinetics, pharmacodynamics, and ultimately the therapeutic response of the different oral glucose-lowering drugs. Indeed several genetic variants are associated with the response to oral glucose-lowering drugs. This review comprises current knowledge on genetic variants affecting both pharmacokinetics and pharmacodynamics of oral glucose-lowering drugs. Included variants are located in genes coding for drug transporters, i.e., the organic anion-transporting family and the organic cation transporter family; genes involved in metabolism, i.e., cytochrome P450 superfamily; genes coding for drug receptors; T2DM-associated genes; and genes identified by genome-wide association studies (GWASs). Furthermore, this review provides insight into current status and future directions for personalized medicine in T2DM.