{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:36:24Z","timestamp":1788298584255,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:00:00Z","timestamp":1622419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102018R1D1A1B07044406"],"award-info":[{"award-number":["NRF\u20102018R1D1A1B07044406"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Metformin is a major treatment for type 2 diabetes. This study was conducted to investigate the impact of gut microbiome dysbiosis on the pharmacokinetics and antihyperglycemic effects of metformin. Healthy adult males aged 19\u201345 years with no defecation abnormalities were recruited for this 4\u2010period clinical study: baseline; post\u2010metformin (i.e., multiple oral doses of 1000\u00a0mg metformin on days 1\u20134); post\u2010vancomycin (i.e., multiple oral doses of 500\u00a0mg vancomycin on days 11\u201317 inducing gut microbiome changes); and post\u2010metformin\u00a0+\u00a0vancomycin (i.e., multiple oral doses of 1000\u00a0mg metformin on days 16\u201319). In each period, serum glucose and insulin concentrations following an oral glucose tolerance test, fecal samples for gut microbiome composition, and safety data were obtained. Following metformin dosing, plasma and urine samples for pharmacokinetics were collected. Nine subjects completed the study. The pharmacokinetics of metformin remained unchanged, and the antihyperglycemic effect was significantly decreased after vancomycin administration (<jats:italic>p<\/jats:italic> value\u00a0=\u00a00.039), demonstrating the weak relationship between the pharmacokinetics and pharmacodynamics of metformin. Relative abundances of some genus were changed after vancomycin administration, and tended to correlate with the antihyperglycemic effects of metformin (<jats:italic>p<\/jats:italic> value\u00a0=\u00a00.062 for <jats:italic>Erysipelatoclostridium<\/jats:italic>; <jats:italic>p<\/jats:italic> value\u00a0=\u00a00.039 for <jats:italic>Enterobacter<\/jats:italic>; and <jats:italic>p<\/jats:italic> value\u00a0=\u00a00.086 for <jats:italic>Faecalibacterium<\/jats:italic>). Adverse events occurred in all subjects and were resolved without sequelae. In conclusion, a decrease in the antihyperglycemic effect of metformin was observed after concomitant administration with vancomycin, without changes in metformin pharmacokinetics. The antihyperglycemic effect was tended to correlate with the relative abundance of several genus, suggesting that the effect of metformin is partly attributable to the gut microbiome (ClinicalTrials.gov, NCT03809260).<\/jats:p>","DOI":"10.1111\/cts.13051","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T08:31:55Z","timestamp":1620894715000},"page":"1955-1966","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Effects of vancomycin\u2010induced gut microbiome alteration on the pharmacodynamics of metformin in healthy male subjects"],"prefix":"10.1111","volume":"14","author":[{"given":"Eunwoo","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew Hyoungjin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Chun","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo\u2010Youn","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital Seoul South Korea"},{"name":"Department of Biomedical Sciences Seoul National University College of Medicine and Hospital Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung\u2010Sang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital Seoul South Korea"},{"name":"Department of Biomedical Sciences Seoul National University College of Medicine and Hospital Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Yong","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Bundang Hospital Seongnam South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/4267357"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4342-z"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12864"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12577"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191258"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.1992.tb01716.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.567"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0000000000000139"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602532.2018.1497647"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4345"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-019-4848-7"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365548.2010.544671"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw383"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.07.008"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx295"},{"key":"e_1_2_9_17_1","unstructured":"MicrobiomeAnalysis.https:\/\/www.microbiomeanalyst.ca\/MicrobiomeAnalyst\/docs\/FaqView.xhtml#lefse. 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