Metformin transporter pharmacogenomics: insights into drug disposition—where are we now?

Paul Chan, Li Shao, Brian Tomlinson, Yuzhen Zhang, Zhong Min Liu

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Introduction: Metformin is recommended as first-line treatment for type 2 diabetes (T2D) by all major diabetes guidelines. With appropriate usage it is safe and effective overall, but its efficacy and tolerability show considerable variation between individuals. It is a substrate for several drug transporters and polymorphisms in these transporter genes have shown effects on metformin pharmacokinetics and pharmacodynamics. Areas covered: This article provides a review of the current status of the influence of transporter pharmacogenomics on metformin efficacy and tolerability. The transporter variants identified to have an important influence on the absorption, distribution, and elimination of metformin, particularly those in organic cation transporter 1 (OCT1, gene SLC22A1), are reviewed. Expert opinion: Candidate gene studies have shown that genetic variations in SLC22A1 and other drug transporters influence the pharmacokinetics, glycemic responses, and gastrointestinal intolerance to metformin, although results are somewhat discordant. Conversely, genome-wide association studies of metformin response have identified signals in the pharmacodynamic pathways rather than the transporters involved in metformin disposition. Currently, pharmacogenomic testing to predict metformin response and tolerability may not have a clinical role, but with additional data from larger studies and availability of safe and effective alternative antidiabetic agents, this is likely to change.

Original languageEnglish
Pages (from-to)1149-1159
Number of pages11
JournalExpert Opinion on Drug Metabolism and Toxicology
Volume14
Issue number11
DOIs
Publication statusPublished - Nov 2 2018

Fingerprint

Metformin
Pharmacogenetics
Pharmaceutical Preparations
Genes
Pharmacodynamics
Pharmacokinetics
Medical problems
Organic Cation Transporter 1
Genome-Wide Association Study
Expert Testimony
Polymorphism
Hypoglycemic Agents
Type 2 Diabetes Mellitus
Availability
Guidelines
Testing
Substrates

Keywords

  • Metformin
  • organic cation transporter
  • pharmacogenomics
  • transporter
  • type 2 diabetes

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Metformin transporter pharmacogenomics : insights into drug disposition—where are we now? / Chan, Paul; Shao, Li; Tomlinson, Brian; Zhang, Yuzhen; Liu, Zhong Min.

In: Expert Opinion on Drug Metabolism and Toxicology, Vol. 14, No. 11, 02.11.2018, p. 1149-1159.

Research output: Contribution to journalReview article

Chan, Paul ; Shao, Li ; Tomlinson, Brian ; Zhang, Yuzhen ; Liu, Zhong Min. / Metformin transporter pharmacogenomics : insights into drug disposition—where are we now?. In: Expert Opinion on Drug Metabolism and Toxicology. 2018 ; Vol. 14, No. 11. pp. 1149-1159.
@article{0a6b3158e50047dfa2a2c6760b5ed5cc,
title = "Metformin transporter pharmacogenomics: insights into drug disposition—where are we now?",
abstract = "Introduction: Metformin is recommended as first-line treatment for type 2 diabetes (T2D) by all major diabetes guidelines. With appropriate usage it is safe and effective overall, but its efficacy and tolerability show considerable variation between individuals. It is a substrate for several drug transporters and polymorphisms in these transporter genes have shown effects on metformin pharmacokinetics and pharmacodynamics. Areas covered: This article provides a review of the current status of the influence of transporter pharmacogenomics on metformin efficacy and tolerability. The transporter variants identified to have an important influence on the absorption, distribution, and elimination of metformin, particularly those in organic cation transporter 1 (OCT1, gene SLC22A1), are reviewed. Expert opinion: Candidate gene studies have shown that genetic variations in SLC22A1 and other drug transporters influence the pharmacokinetics, glycemic responses, and gastrointestinal intolerance to metformin, although results are somewhat discordant. Conversely, genome-wide association studies of metformin response have identified signals in the pharmacodynamic pathways rather than the transporters involved in metformin disposition. Currently, pharmacogenomic testing to predict metformin response and tolerability may not have a clinical role, but with additional data from larger studies and availability of safe and effective alternative antidiabetic agents, this is likely to change.",
keywords = "Metformin, organic cation transporter, pharmacogenomics, transporter, type 2 diabetes",
author = "Paul Chan and Li Shao and Brian Tomlinson and Yuzhen Zhang and Liu, {Zhong Min}",
year = "2018",
month = "11",
day = "2",
doi = "10.1080/17425255.2018.1541981",
language = "English",
volume = "14",
pages = "1149--1159",
journal = "Expert Opinion on Drug Metabolism and Toxicology",
issn = "1742-5255",
publisher = "Informa Healthcare",
number = "11",

}

TY - JOUR

T1 - Metformin transporter pharmacogenomics

T2 - insights into drug disposition—where are we now?

AU - Chan, Paul

AU - Shao, Li

AU - Tomlinson, Brian

AU - Zhang, Yuzhen

AU - Liu, Zhong Min

PY - 2018/11/2

Y1 - 2018/11/2

N2 - Introduction: Metformin is recommended as first-line treatment for type 2 diabetes (T2D) by all major diabetes guidelines. With appropriate usage it is safe and effective overall, but its efficacy and tolerability show considerable variation between individuals. It is a substrate for several drug transporters and polymorphisms in these transporter genes have shown effects on metformin pharmacokinetics and pharmacodynamics. Areas covered: This article provides a review of the current status of the influence of transporter pharmacogenomics on metformin efficacy and tolerability. The transporter variants identified to have an important influence on the absorption, distribution, and elimination of metformin, particularly those in organic cation transporter 1 (OCT1, gene SLC22A1), are reviewed. Expert opinion: Candidate gene studies have shown that genetic variations in SLC22A1 and other drug transporters influence the pharmacokinetics, glycemic responses, and gastrointestinal intolerance to metformin, although results are somewhat discordant. Conversely, genome-wide association studies of metformin response have identified signals in the pharmacodynamic pathways rather than the transporters involved in metformin disposition. Currently, pharmacogenomic testing to predict metformin response and tolerability may not have a clinical role, but with additional data from larger studies and availability of safe and effective alternative antidiabetic agents, this is likely to change.

AB - Introduction: Metformin is recommended as first-line treatment for type 2 diabetes (T2D) by all major diabetes guidelines. With appropriate usage it is safe and effective overall, but its efficacy and tolerability show considerable variation between individuals. It is a substrate for several drug transporters and polymorphisms in these transporter genes have shown effects on metformin pharmacokinetics and pharmacodynamics. Areas covered: This article provides a review of the current status of the influence of transporter pharmacogenomics on metformin efficacy and tolerability. The transporter variants identified to have an important influence on the absorption, distribution, and elimination of metformin, particularly those in organic cation transporter 1 (OCT1, gene SLC22A1), are reviewed. Expert opinion: Candidate gene studies have shown that genetic variations in SLC22A1 and other drug transporters influence the pharmacokinetics, glycemic responses, and gastrointestinal intolerance to metformin, although results are somewhat discordant. Conversely, genome-wide association studies of metformin response have identified signals in the pharmacodynamic pathways rather than the transporters involved in metformin disposition. Currently, pharmacogenomic testing to predict metformin response and tolerability may not have a clinical role, but with additional data from larger studies and availability of safe and effective alternative antidiabetic agents, this is likely to change.

KW - Metformin

KW - organic cation transporter

KW - pharmacogenomics

KW - transporter

KW - type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85056514934&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056514934&partnerID=8YFLogxK

U2 - 10.1080/17425255.2018.1541981

DO - 10.1080/17425255.2018.1541981

M3 - Review article

C2 - 30375241

AN - SCOPUS:85056514934

VL - 14

SP - 1149

EP - 1159

JO - Expert Opinion on Drug Metabolism and Toxicology

JF - Expert Opinion on Drug Metabolism and Toxicology

SN - 1742-5255

IS - 11

ER -