Endocrinology & Metabolic Syndrome

Oral antidiabetic drugs (OADs) are widely used to treat type 2 diabetes mellitus (T2DM). However, inherited difference is one of the major issues that affect OADs therapeutic efficacy. In the present paper, we performed a critical review on recent advances in genetic polymorphisms that influence OADs therapeutic efficacy and metabolism. Sulfonylureas (SUs), Meglitinides, Metformin and Thiazolidinediones (TZDs) will be discussed. *Corresponding author: Zhao-Qian Liu, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan 410078, China, Tel: +86 731 84805380; Fax: +86-731-82354476; E-mail: [email protected] Received December 01, 2011; Accepted January 16, 2012; Published January 18, 2012 Citation: Yin J, Guo Y, Huang Q, Sun H, Zhou H, et al. (2012) Pharmacogenetics of Oral Antidiabetic Drugs: Potential Clinical Application. Endocrinol Metab Synd S5:003. doi:10.4172/2161-1017.S5-003 Copyright: © 2012 Yin J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. conclusion of correlation of CYP2C9 polymorphisms and sulfonylurea treatment efficacy needs further confirmation. Polymorphisms of KCNJ11: KCNJ11 encodes Kir6.2, which is a subunit of KATP channel. KCNJ11 polymorphisms and sulfonylurea response in T2DM patients was widely studied. The most intensively investigated polymorphism is Glu23Lys (E23K) [10-12]. It was hypothesized that K23 allele may be associated with interindividual variability of sulfonylurea response. This hypothesis was tested in a group of newly diagnosed diabetes patients treated with Sulfonylureas [10]. However, in this study, the KCNJ11 E23K variant was not significantly associated with patients’ response to sulfonylurea. In another study, Sesti et al. [13] showed that E23K variant was associated with an increased risk of secondary sulfonylurea failure in T2DM patients. Thus, the correlation between KCNJ11 E23K variant and sulfonylurea response in T2DM patients need more investigations. Polymorphisms of TCF7L2: Among T2DM associated genes, TCF7L2 were widely studied. It correlated with an increased risk of T2DM in several populations [14]. It was reported that TCF7L2 polymorphisms influence the initial success treatment of sulfonylurea in T2DM patients. The most intensively studied polymorphisms are rs12255372 and rs7903146, which were associated with diabetes risk. In a study of large sample size T2DM patients, risk allele carriers of rs12255372 and rs7903146 were more sensitive to sulfonylurea. However, no association was detected for metformin [15]. Sulfonylurea therapy is safe and effective for a short term use in most patients and may successfully replace treatment with insulin injections [16]. It dramatically improves glycemic control and should be considered as the first line drug for patients with poor glycemic control on an appropriate diet [17]. However, polymorphisms of above mentioned genes need to be considered when using SUs.