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Clin Pharmacol Ther. 2017 Jun;101(6):763-772. doi: 10.1002/cpt.567. Epub 2017 Feb 3.

Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis.

Author information

1
Department of Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.
2
Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK.
3
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA.
4
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
5
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
6
Inspectorate of Healthcare, Utrecht, The Netherlands.
7
Department of Internal Medicine 4, Faculty of Medicine, Šafárik University, Košice, Slovakia.
8
Pasteur University Hospital, Košice, Slovakia.
9
Latvian Biomedical Research and Study Centre, Riga, Latvia.
10
Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
11
Treant Zorggroep, Location Bethesda, Hoogeveen, The Netherlands.
12
Bethesda Diabetes Research Centre, Hoogeveen, The Netherlands.
13
Core for Genomic Medicine, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
14
Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
15
Department of General Practice, EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
16
Department of Medical Biology, Faculty of Medicine, Šafárik University, Košice, Slovakia.
17
Department of Public Health, Clinical Pharmacology and Pharmacy, University of Southern Denmark, Odense, Denmark.
18
International University of Sarajevo, Faculty of Engineering and Natural Sciences, Sarajevo, Bosnia and Herzegovina.
19
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
20
Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
21
Department of Epidemiology and Biostatistics, EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
22
Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.

Abstract

Therapeutic response to metformin, a first-line drug for type 2 diabetes (T2D), is highly variable, in part likely due to genetic factors. To date, metformin pharmacogenetic studies have mainly focused on the impact of variants in metformin transporter genes, with inconsistent results. To clarify the significance of these variants in glycemic response to metformin in T2D, we performed a large-scale meta-analysis across the cohorts of the Metformin Genetics Consortium (MetGen). Nine candidate polymorphisms in five transporter genes (organic cation transporter [OCT]1, OCT2, multidrug and toxin extrusion transporter [MATE]1, MATE2-K, and OCTN1) were analyzed in up to 7,968 individuals. None of the variants showed a significant effect on metformin response in the primary analysis, or in the exploratory secondary analyses, when patients were stratified according to possible confounding genotypes or prescribed a daily dose of metformin. Our results suggest that candidate transporter gene variants have little contribution to variability in glycemic response to metformin in T2D.

PMID:
27859023
PMCID:
PMC5425333
DOI:
10.1002/cpt.567
[Indexed for MEDLINE]
Free PMC Article

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