{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T06:13:03Z","timestamp":1793167983771,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>This study evaluates how changes in intestinal bile acid composition, induced by cholestyramine, a bile acid sequestrant, affect metformin's pharmacodynamics (PD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An open\u2010label, 2\u2010period 1\u2010sequence crossover study was conducted with healthy male adults. Each period consisted of both before and after metformin treatments. Cholestyramine was administered during the second period to change the bile acid pool. For, PD assessment, an oral glucose tolerance test was conducted at each treatment in both periods. Metformin was administered 3 times during each period, and cholestyramine was administered 3 times per day for 7\u00a0days during the second period. Maximum serum glucose concentration, area under the glucose concentration curve and homeostatic model assessment of insulin resistance were calculated. Baseline\u2010corrected PD parameters were derived by subtracting pre\u2010metformin values from post\u2010metformin values. Lipid and panels and bile acid profiles in stool were measured. Adverse events were monitored throughout the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fourteen subjects completed the study. The mean values of 3 PD parameters were all decreased after metformin administration in both periods. Cholestyramine administration led to a further decrease in baseline\u2010corrected PD parameters, significantly reducing the area under the glucose concentration curve by 44.7%. Diarrhoea, the most common adverse event, was reported in 10 subjects during the metformin alone treatment and in 1 subject during the cholestyramine combined treatment (<jats:italic>P<\/jats:italic>\u00a0&lt;\u2009.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Cholestyramine affected the glucose\u2010lowering effect of metformin by the possible change in the bile acid pool in the gut, and metformin\u2010associated diarrhoea was improved by cholestyramine.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16358","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T23:34:22Z","timestamp":1733182462000},"page":"1208-1215","source":"Crossref","is-referenced-by-count":5,"title":["Influence of gut bile acid composition on the glucose\u2010lowering effect and safety of metformin"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5281-8811","authenticated-orcid":false,"given":"Deok Yong","family":"Yoon","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":"Jungeun","family":"Kim","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  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0971-6024","authenticated-orcid":false,"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  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4188-2786","authenticated-orcid":false,"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 Republic of 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