Variants in pharmacokinetic transporters and glycemic response to metformin: A metgen meta-analysis

T. Dujic, K. Zhou, S. W. Yee, N. van Leeuwen, C. E. de Keyser, M. Javorský, S. Goswami, L. Zaharenko, M. M. H. Christiansen, Mattijs Out, R. Tavendale, M. Kubo, M. M. Hedderson, A. A. van der Heijden, L. Klimčáková, V. Pirags, A. Kooy, K. Brøsen, J. Klovins, S. SemizI. Tkáč, B. H. Stricker, C. N. A. Palmer, L. M. 't Hart, K. M Giacomini, E. R. Pearson

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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 transporters genes, with inconsistent results. To clarify the significance of these variants in glycaemic response to metformin in T2D, we performed a large-scale meta-analysis across the cohorts of Metformin Genetics Consortium (MetGen). Nine candidate polymorphisms in five transporter genes (OCT1, OCT2, MATE1, MATE2-K and OCTN1) were analysed 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 metformin daily dose. Our results suggest that candidate transporters genes variants have little contribution to variability in glycaemic response to metformin in T2D.
Original languageEnglish
Pages (from-to)763-772
Number of pages10
JournalClinical Pharmacology & Therapeutics
Volume101
Issue number6
Early online date10 Nov 2016
DOIs
Publication statusPublished - Jun 2017

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