Abstract
Precision medicine is a scientific and medical practice for personalized therapy based on patients’ individual genetic, environmental, and lifestyle characteristics. Pharmacogenetics and pharmacogenomics are also rapidly developing and expanding as a key element of precision medicine, in which the association between individual genetic variabilities and drug disposition and therapeutic responses are investigated. Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia mainly associated with insulin resistance, with the risk of clinically important cardiovascular, neurological, and renal complications. The latest consensus report from the American Diabetes Association and European Association for the Study of Diabetes (ADA-EASD) on the management of T2D recommends preferential use of glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and some dipeptidyl peptidase-4 (DPP-4) inhibitors after initial metformin monotherapy for diabetic patients with established atherosclerotic cardiovascular or chronic kidney disease, and with risk of hypoglycemia or body weight-related problems. In this review article, we summarized current progress on pharmacogenetics of newer second-line antidiabetic medications in clinical practices and discussed their therapeutic implications for precision medicine in T2D management. Several biomarkers associated with drug responses have been identified from extensive clinical pharmacogenetic studies, and functional variations in these genes have been shown to significantly affect drug-related glycemic control, adverse reactions, and risk of diabetic complications. More comprehensive pharmacogenetic research in various clinical settings will clarify the therapeutic implications of these genes, which may be useful tools for precision medicine in the treatment and prevention of T2D and its complications.
Highlights
Precision medicine is a scientific and medical practice in which patients are provided tailored treatments based on their individual characteristics including genetic, environmental, and lifestyle factors [1]
DBPaPs-e4dInohnibthitiosrpsaradigm shift to patient-centered Type 2 diabetes (T2D) treatment strategy, we summarized and reviewed current progress in pharmacogenetics of these new-generation second-line antidiabetic agentsThine cclionnicceapl pt roafct“icinecsraentidn deifsfceucts”sewdatshefiirrsttherreacpoeguntizicedimipnlitchaetio1n9s60fos,r pbyrecthiseioonbmseerdviactiinoen inthtahte meannteargaelmgelnutcoosfeT2aDdmanindisittsractoiomnplpicraotvioidnesd. a more potent insulinotropic stimulus in pancreas compared with isoglycemic intravenous infusion [16]
dipeptidyl peptidase-4 (DPP-4) inhibitors are still attractive second-line medications as they can be orally available, leading to increased patient compliance in T2D patients compared with glucagon-like peptide-1 (GLP-1) receptor agonists which are administered by subcutaneous injection [31]
Summary
Precision medicine is a scientific and medical practice in which patients are provided tailored treatments based on their individual characteristics including genetic, environmental, and lifestyle factors [1]. A number of studies have demonstrated that the major clinically important genes related to metformin treatment are responsible for the expression of solute carrier (SLC)-type transporters, such as organic cation transporter (OCT) 1 (SLC22A1), OCT2 (SLC22A2), multidrug and toxin extrusion (MATE) 1 (SLC47A1), and MATE2-K (SLC47A2) [11,12,13]. These transporters are mainly located in human hepatocytes and renal proximal tubules [14] and are responsible for the plasma exposure of metformin, leading to its clinical efficacy on blood glucose, glycated hemoglobin (HbA1c), and insulin sensitivity.
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