TY - JOUR
T1 - Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin
T2 - A Metgen Meta-Analysis
AU - Dujic, T.
AU - Zhou, K.
AU - Yee, S. W.
AU - van Leeuwen, N.
AU - de Keyser, C. E.
AU - Javorský, M.
AU - Goswami, S.
AU - Zaharenko, L.
AU - Hougaard Christensen, M. M.
AU - Out, M.
AU - Tavendale, R.
AU - Kubo, M.
AU - Hedderson, M. M.
AU - van der Heijden, A. A.
AU - Klimčáková, L.
AU - Pirags, V.
AU - Kooy, A.
AU - Brøsen, K.
AU - Klovins, J.
AU - Semiz, S.
AU - Tkáč, I.
AU - Stricker, B. H.
AU - Palmer, C. N.A.
AU - 't Hart, L. M.
AU - Giacomini, K. M.
AU - Pearson, E. R.
N1 - Publisher Copyright:
© 2017 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85012060225
UR - https://www.scopus.com/pages/publications/85012060225#tab=citedBy
U2 - 10.1002/cpt.567
DO - 10.1002/cpt.567
M3 - Article
C2 - 27859023
AN - SCOPUS:85012060225
SN - 0009-9236
VL - 101
SP - 763
EP - 772
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 6
ER -
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