Diabetes: Is There A Future For Pharmacogenomics Guided Treatment?
Ewan R. Pearson
Published 2019 · Medicine
Download PDFAnalyze on Scholarcy
Diabetes is a disease defined on the basis of hyperglycemia. There are monogenic forms of diabetes where defining the genetic cause has a dramatic impact on treatment—with patients being able to transition from insulin to sulfonylureas. However, the majority of diabetes is type 2 diabetes. This review outlines the robust evidence accrued to date for pharmacogenetics of metformin, sulfonylureas, thiazolidinediones, and dipeptidyl peptidase‐4 inhibitors but highlights that these variants will only be of clinical utility when the genotype is already known at the point of prescribing. The future of pharmacogenetics in diabetes and other common complex disease relies on a paradigm shift—that of preemptive panel genotyping and use of clinical decision support tools to assimilate this genetic information with other clinical phenotypic data and to present this information simply to the prescriber. Given the recent dramatic fall in genotyping costs, this future is not far off.
This paper references
Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota
Kristoffer Forslund (2015)
The systematic application of non-destructive testing techniques for ancient wood buildings
Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug
Hao Wu (2017)
Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes
Struan F A Grant (2006)
Type 2 diabetes genetic loci informed by multi-trait associations point to disease mechanisms and subtypes: A soft clustering analysis
Miriam S Udler (2018)
Effects of Pro12Ala polymorphism of peroxisome proliferator-activated receptor gamma2 gene on rosiglitazone response in type 2 diabetes.
Eun Seok Kang (2005)
The genetic architecture of type 2 diabetes
Christian Fuchsberger (2016)
Pharmacogenomics in diabetes mellitus: insights into drug action and drug discovery
Kaixin Zhou (2016)
Involvement of organic cation transporter 3 (Oct3/Slc22a3) in the bioavailability and pharmacokinetics of antidiabetic metformin in mice.
Yoshiyuki Shirasaka (2016)
Repurposing metformin for the prevention of cancer and cancer recurrence
Brandy M. Heckman-Stoddard (2017)
Metformin and the gastrointestinal tract
Laura J McCreight (2015)
Influence of CYP2C9 and CYP2C19 genetic polymorphisms on pharmacokinetics of gliclazide MR in Chinese subjects.
Yifan Zhang (2007)
Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables.
Emma Ahlqvist (2018)
Association of sulfonylurea receptor 1 genotype with therapeutic response to gliclazide in type 2 diabetes.
Huijuan Zhang (2007)
Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes.
Anna L. Gloyn (2004)
Metformin and ageing: improving ageing outcomes beyond glycaemic control
Willy Marcos Valencia (2017)
PPAR-γ2 and PTPRD gene polymorphisms influence type 2 diabetes patients' response to pioglitazone in China
Qi Pei (2013)
Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps
Anubha Mahajan (2018)
KCNJ11 E23K variant is associated with the therapeutic effect of sulphonylureas in Chinese type 2 diabetic patients.
Qing Li (2014)
influence on response to oral hypoglycemic agents
A. Y. Dawed (2016)
Interaction between variants in the CYP2C9 and POR genes and the risk of sulfonylurea‐induced hypoglycaemia: A GoDARTS Study
Tanja Dujic (2018)
Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study
Tanja Dujic (2014)
Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.
Andrey P. Babenko (2006)
Variation in the Glucose Transporter gene SLC2A2 is associated with glycaemic response to metformin
Kaixin Zhou (2016)
Cytochrome P450 2C9 *2 and *3 polymorphisms and the dose and effect of sulfonylurea in type II diabetes mellitus.
Matthijs L. Becker (2008)
A soft clustering analysis
present clinical challenges
S. Misra (2018)
The CTRB 1 / 2 locus affects
L. M. t Hart (2005)
Pharmacogenetics in type 2 diabetes: influence on response to oral hypoglycemic agents
Adem Y Dawed (2016)
insights into drug action and drug discovery
K. Zhou (2016)
Common polymorphisms of the peroxisome proliferator-activated receptor-gamma (Pro12Ala) and peroxisome proliferator-activated receptor-gamma coactivator-1 (Gly482Ser) and the response to pioglitazone in Chinese patients with type 2 diabetes mellitus.
Ming-Chia Hsieh (2010)
Prevalence of vascular complications among patients with glucokinase mutations and prolonged, mild hyperglycemia.
Anna M. Steele (2014)
Association studies of variants in promoter and coding regions of beta-cell ATP-sensitive K-channel genes SUR1 and Kir6.2 with Type 2 diabetes mellitus (UKPDS 53).
Anna L. Gloyn (2001)
The CTRB1/2 Locus Affects Diabetes Susceptibility and Treatment via the Incretin Pathway
Leen M 't Hart (2013)
Recessive mutations in the cancer gene Ataxia Telangiectasia Mutated (ATM), at a locus previously associated with metformin response, cause dysglycaemia and insulin resistance
Paul J Connelly (2016)
Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations.
Ewan R. Pearson (2006)
Association studies of variants in promoter and coding regions of beta- cell ATP- sensitive K- channel genes SUR1 and Kir6.2 with Type 2 diabetes mellitus (UKPDS 53)
The Role of Pharmacogenetics in Drug Disposition and Response of Oral Glucose-Lowering Drugs
Nienke Leeuwen (2013)
Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide
Martin Javorský (2013)
Effect of sulphonylurea treatment on glycaemic control is related to TCF7L2 genotype in patients with type 2 diabetes.
Zbyněk Schroner (2011)
Sex and BMI Alter the Benefits and Risks of Sulfonylureas and Thiazolidinediones in Type 2 Diabetes: A Framework for Evaluating Stratification Using Routine Clinical and Individual Trial Data
John M Dennis (2018)
No deterioration in glycemic control in HNF-1alpha maturity-onset diabetes of the young following transfer from long-term insulin to sulphonylureas.
Maggie H Shepherd (2003)
A GoDARTS Study
T. Dujic (2018)
Pharmacogenomic analysis of ATP-sensitive potassium channels coexpressing the common type 2 diabetes risk variants E23K and S1369A.
Veronica Lang (2012)
Effects of CYP2C19 and CYP2C9 genetic polymorphisms on the disposition of and blood glucose lowering response to tolbutamide in humans.
Ji-Hong Shon (2002)
Cross-sectional and longitudinal studies suggest pharmacological treatment used in patients with glucokinase mutations does not alter glycaemia
Amanda Stride (2013)
Impact of CYP2C9 amino acid polymorphisms on glyburide kinetics and on the insulin and glucose response in healthy volunteers.
Julia Kirchheiner (2002)
susceptibil - ity and treatment via the incretin pathway
A. Mahajan (2013)
CYP2C8 and SLCO1B1 Variants and Therapeutic Response to Thiazolidinediones in Patients With Type 2 Diabetes
Adem Y Dawed (2016)
Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes
Kaixin Zhou (2011)
Genetic cause of hyperglycaemia and response to treatment in diabetes
Ewan R. Pearson (2003)
Heritability of variation in glycaemic response to metformin: a genome-wide complex trait analysis
Kaixin Zhou (2014)
Genetics of Monogenic Diabetes: Present Clinical Challenges
S Misra (2018)
HLA-B*5701 screening for hypersensitivity to abacavir.
Simon A Mallal (2008)
Ser1369Ala Variant in Sulfonylurea Receptor Gene ABCC8 Is Associated With Antidiabetic Efficacy of Gliclazide in Chinese Type 2 Diabetic Patients
Yan Feng (2008)
TCF7L2 Genetic Variation Augments Incretin Resistance and Influences Response to a Sulfonylurea and Metformin: The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH)
Shylaja Srinivasan (2018)
Pharmacokinetics of glimepiride and cytochrome P450 2C9 genetic polymorphisms.
Rui Wang (2005)
The mechanisms of action of metformin
Graham Rena (2017)
Effect of Serotonin Transporter 5-HTTLPR Polymorphism on Gastrointestinal Intolerance to Metformin: A GoDARTS Study
Tanja Dujic (2016)
This paper is referenced by
Genetic predisposition in Type 2 Diabetes: a promising approach towards a personalized management of diabetes.
Mahmoud M Sirdah (2020)
Pharmacogenetics: Chasing Perfection.
Andrea Gaedigk (2019)