{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:33:15Z","timestamp":1789421595468,"version":"build-2803163510"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018866","name":"RECETOX P\u0159\u00edrodov\u011bdeck\u00e9 Fakulty Masarykovy Univerzity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a T\u011blov\u00fdchovy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Metformin is a widely used drug with a relatively good efficacy in diabetes treatment, a good safety profile, and the potential for use in other indications. The variability in the individual responses to metformin therapy is partially determined by genetic factors. This narrative review aimed to summarize information on single nucleotide variant (SNVs) in genes for transporter proteins associated with metformin pharmacokinetics and pharmacodynamics and\/or the occurrence of adverse effects. The Pharmacogenomics Knowledge Base (PharmGKB) and Web of Science databases were searched for metformin-associated gene variants that could affect its action. Seven transporter genes with twelve SNVs common in the European population were identified in the PharmGKB database, namely SNVs in genes\n                    <jats:italic>SLC22A1<\/jats:italic>\n                    (OCT1),\n                    <jats:italic>SLC22A2<\/jats:italic>\n                    (OCT2),\n                    <jats:italic>SLC22A3<\/jats:italic>\n                    (OCT3),\n                    <jats:italic>SLC22A4<\/jats:italic>\n                    (OCTN1),\n                    <jats:italic>SLC47A1<\/jats:italic>\n                    (MATE1),\n                    <jats:italic>SLC47A2<\/jats:italic>\n                    (MATE2-K)\n                    <jats:italic>,<\/jats:italic>\n                    and\n                    <jats:italic>SLC2A2<\/jats:italic>\n                    (GLUT2); it is worth noting that GLUT2 is not metformin transported but a glucose transporter and as such, it can also influence metformin action. Based on 63 retrieved studies, the association of individual SNVs with metformin effectiveness and adverse effects is discussed. In view of the high variability of study designs, populations, and reporting patterns, we also propose a framework for the design and reporting of metformin-associated pharmacogenetic studies, suggesting also that determining a complete set of these SNVs could help in comprehensive understanding of genetically conditioned individual responsiveness to metformin therapy, thus opening the path to maximizing the utilization of its positive effects while minimizing the risk of adverse effects. In addition, given the large variability in designs among studies, we also propose a framework for future studies on SNVs in metformin action-associated transporters that could improve comparability of future studies.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1794405","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:48:27Z","timestamp":1781848107000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Transporter gene variants influencing metformin pharmacokinetics and pharmacodynamics common in European populations: a pharmacogenetic narrative review"],"prefix":"10.3389","volume":"17","author":[{"given":"Natalie","family":"Mlcuchova","sequence":"first","affiliation":[{"name":"RECETOX, Faculty of Science, Masaryk University","place":["Brno, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bretislav","family":"Lipovy","sequence":"additional","affiliation":[{"name":"RECETOX, Faculty of Science, Masaryk University","place":["Brno, Czechia"]},{"name":"Department of Burns Medicine, Third Faculty of Medicine, Charles University and University Hospital Kralovske Vinohrady","place":["Prague, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ondrej","family":"Zendulka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Masaryk University","place":["Brno, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslav","family":"Janosek","sequence":"additional","affiliation":[{"name":"RECETOX, Faculty of Science, Masaryk University","place":["Brno, Czechia"]},{"name":"Centre for Health Research, Faculty of Medicine, University of Ostrava","place":["Ostrava, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Borilova Linhartova","sequence":"additional","affiliation":[{"name":"RECETOX, Faculty of Science, Masaryk University","place":["Brno, Czechia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.2478\/bjmg-2021-0004","article-title":"Genetic association of solute carrier transporter gene variants with metformin response","volume":"24","author":"Abrahams-October","year":"2021","journal-title":"Balk. 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