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Expert Review of Clinical Pharmacology Volume 15, 2022 - Issue 9
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Review

Effects of single-nucleotide polymorphism on the pharmacokinetics and pharmacodynamics of metformin

Shaoqian Lia The First Affiliated Hospital, Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, China;b The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China;c The First Affiliated Hospital, Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hengyang Medical School, University of South China, Hengyang, Hunan, ChinaView further author information
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Bo Xua The First Affiliated Hospital, Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, China;b The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, ChinaView further author information
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Shangzhi Fana The First Affiliated Hospital, Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, China;b The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China;c The First Affiliated Hospital, Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hengyang Medical School, University of South China, Hengyang, Hunan, ChinaView further author information
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Bo Kanga The First Affiliated Hospital, Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, China;b The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China;c The First Affiliated Hospital, Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hengyang Medical School, University of South China, Hengyang, Hunan, ChinaView further author information
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Lijing Denga The First Affiliated Hospital, Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, China;b The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China;d The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, ChinaView further author information
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Danjun Chena The First Affiliated Hospital, Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, China;b The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China;d The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, ChinaView further author information
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Bo Yanga The First Affiliated Hospital, Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, China;b The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China;d The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, ChinaView further author information
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Fan Tanga The First Affiliated Hospital, Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, China;b The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China;d The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, ChinaView further author information
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Zunbo Hea The First Affiliated Hospital, Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, China;b The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China;e The First Affiliated Hospital, Department of Anesthesiology, Hengyang Medical School, University of South China, Hengyang, Hunan, ChinaView further author information
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Yong Xuef The Second Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, ChinaView further author information
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Jie-Can Zhoua The First Affiliated Hospital, Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, Hunan, China;b The First Affiliated Hospital, Hengyang Key Laboratory of Clinical Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China;c The First Affiliated Hospital, Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hengyang Medical School, University of South China, Hengyang, Hunan, China;d The First Affiliated Hospital, Pharmacy Department, Hengyang Medical School, University of South China, Hengyang, Hunan, ChinaCorrespondence[email protected] [email protected] [email protected]
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Pages 1107-1117 | Received 16 May 2022, Accepted 22 Aug 2022, Published online: 05 Sep 2022
 
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ABSTRACT

Introduction

Metformin has been recognized as the first-choice drug for type 2 diabetes mellitus (T2DM). The potency of metformin in the treatment of type 2 diabetes has always been in the spotlight and shown significant individual differences. Based on previous studies, the efficacy of metformin is related to the single-nucleotide polymorphisms of transporter genes carried by patients, amongst which a variety of gene polymorphisms of transporter and target protein genes affect the effectiveness and adverse repercussion of metformin.

Areas covered

Here, we reviewed the current knowledge about gene polymorphisms impacting metformin efficacy based on transporter and drug target proteins.

Expert opinion

The reason for the difference in clinical drug potency of metformin can be attributed to the gene polymorphism of drug transporters and drug target proteins in the human body. Substantial evidence shows that genetic polymorphisms in transporters such as organic cation transporter 1 (OCT1) and organic cation transporter 2 (OCT2) affect the glucose-lowering effectiveness of metformin. However, optimization of individualized dosing regimens of metformin is necessary to clarify the role of several polymorphisms.

Article highlights

  • The genetic polymorphisms altering the potency of metformin were summarized.

  • The research emphases and gaps of metformin-related gene polymorphism were described in detail.

  • Gene polymorphisms impacting metformin effectiveness were explained from pharmacokinetic and pharmacodynamic perspectives.

  • Each SNP is explained and discussed in detail.

  • This manuscript provides a reference for metformin pharmacogenomic exploration.

Author contributions

S Li contributed to the conception of the study; B Xu, S Fan and B Kang performed the data analyses and wrote the manuscript; L Deng, D Chen, B Yang, F Tang, Z He and Y Xue performed the analysis with constructive discussions; J-C Zhou contributed significantly to manuscript preparation.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (No. 82003872), Natural Science Foundation of Hunan Province (No.2020JJ5513, No. 2022JJ50163), Hunan Province Clinical Medical Technology Innovation Guidance Project (No.2020SK51823), Funds of the central government guiding local scientific and technological development (No.2021QZY016), Scientific Research Fund Project of Hunan Provincial Health Commission (No.20201973), Scientific research Fund of Hunan provincial education department (No.19A418) and Postgraduate Scientific Research Innovation Project of Hunan Province (No.CX20210974).

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