Interindividual variability in oral antidiabetic drug disposition and response: the role of drug transporter polymorphisms.

BACKGROUND: Numerous effective oral pharmacologic therapies are available to treat type 2 diabetes. However, a substantial number of patients do not achieve the expected glucose-lowering response, or may be predisposed to adverse effects, from these agents. The application of pharmacogenetics to the field of type 2 diabetes is one step towards the goal of improved pharmacotherapeutic management of this progressive disease.
METHODS: A PubMed literature search was conducted to identify clinical studies that have examined the extent to which drug-transporter gene polymorphisms influence interindividual variability in oral antidiabetic drug disposition and response in humans. RESULTS/
CONCLUSION: Available data suggest that drug transporters play an important role in the disposition of some oral antidiabetic drugs in the body, particularly the meglitinides and metformin. Moreover, polymorphisms in genes encoding drug transport proteins may alter the pharmacodynamic profile of these agents. Drug transporters, drug-metabolizing enzymes, and drug targets each play a distinct and important role in the disposition and action of many oral antidiabetic agents. Thus, future studies may need to take a pharmacogenomic (i.e., multiple gene) approach in order to comprehensively understand the extent to which genetic variation contributes to interindividual differences in oral antidiabetic drug clinical pharmacology.