{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:15:55Z","timestamp":1790806555943,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,3,23]],"date-time":"2018-03-23T00:00:00Z","timestamp":1521763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To assess potential causes of metformin intolerance, including altered metformin uptake from the intestine, increased anaerobic glucose utilization and subsequent lactate production, altered serotonin uptake, and altered bile acid pool.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>For this pharmacokinetic study, we recruited 10 severely intolerant and 10 tolerant individuals, matched for age, sex and body mass index. A single 500\u2010mg dose of metformin was administered, with blood sampling at 12 time points over 24 hours. Blood samples were analysed for metformin, lactate, serotonin and bile acid concentrations, and compared across the phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The intolerant individuals were severely intolerant to 500 mg metformin. No significant difference was identified between tolerant and intolerant cohorts in metformin pharmacokinetics: median (interquartile range [IQR]) peak concentration 2.1 (1.7\u20102.3) mg\/L and 2.0 (1.8\u20102.2) mg\/L, respectively (\n                      <jats:italic>P<\/jats:italic>\n                      = .76); time to peak concentration 2.5 hours; median (IQR) area under the curve (AUC)\n                      <jats:sub>0\u201324<\/jats:sub>\n                      16.9 (13.9\u201018.6) and 13.9 (12.9\u201016.8) mg\/L*h, respectively (\n                      <jats:italic>P<\/jats:italic>\n                      = .72). Lactate concentration peaked at 3.5 hours, with mean peak concentration of 2.4 mmol\/L in both cohorts (95% CI 2.0\u20102.8 and 1.8\u20103.0 mmol\/L, respectively), and similar incremental AUC\n                      <jats:sub>0\u201324<\/jats:sub>\n                      in each cohort: tolerant cohort 6.98 (95% CI 3.03\u201010.93) and intolerant cohort 4.47 (95% CI \u20133.12\u201012.06) mmol\/L*h (\n                      <jats:italic>P<\/jats:italic>\n                      = .55). Neither serotonin nor bile acid concentrations were significantly different.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Despite evidence of severe intolerance in our cohort, there was no significant difference in metformin pharmacokinetics or systemic measures of lactate, serotonin or bile acids. This suggests that metformin intolerance may be attributable to local factors within the lumen or enterocyte.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13264","type":"journal-article","created":{"date-parts":[[2018,2,21]],"date-time":"2018-02-21T13:12:39Z","timestamp":1519218759000},"page":"1593-1601","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Pharmacokinetics of metformin in patients with gastrointestinal intolerance"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0880-4818","authenticated-orcid":false,"given":"Laura J.","family":"McCreight","sequence":"first","affiliation":[{"name":"Division of Molecular and Clinical Medicine Ninewells Hospital and Medical School  Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tore B.","family":"Stage","sequence":"additional","affiliation":[{"name":"Department of Public Health, Clinical 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