Pharmacogenetics of thiazolidinedione therapy

Abstract

The thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor-γ agonists and have glucose-lowering, insulin-sensitizing and anti-inflammatory effects. TZDs are approved for the treatment of Type 2 diabetes, and have been studied as a diabetes-prevention strategy. Despite widespread use of TZDs, a large number of patients fail to achieve a substantial reduction in glucose, or an improvement in insulin sensitivity, following treatment. Available data suggest that polymorphisms in genes encoding TZD drug targets, effector proteins and metabolizing enzymes contribute to the observed interindividual variability in TZD response and disposition. The purpose of this review is to highlight recent developments in the field of TZD pharmacogenetics, specifically focusing on clinical studies that have investigated genetic determinants of TZD response (i.e., reduction in glycemia and improvement in insulin sensitivity), disposition (i.e., pharmacokinetics), and side effects in patients with Type 2 diabetes and patients at risk for Type 2 diabetes.