{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T09:37:32Z","timestamp":1780565852900,"version":"3.54.1"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,11,20]],"date-time":"2014-11-20T00:00:00Z","timestamp":1416441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To provide model\u2010based clinical development decision support including dose selection guidance for empagliflozin, an orally administered sodium glucose cotransporter 2 inhibitor, through developed exposure\u2212response (<jats:styled-content style=\"fixed-case\">E\u2212R<\/jats:styled-content>) models for efficacy and tolerability in patients with type 2 diabetes mellitus (<jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Five randomized, placebo\u2010controlled, multiple oral dose studies of empagliflozin in patients with <jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content> (<jats:italic>n<\/jats:italic> = 974; 1\u2013100\u2009mg once daily, duration \u226412 weeks) were used to develop <jats:styled-content style=\"fixed-case\">E\u2212R<\/jats:styled-content> models for efficacy (glycosylated haemoglobin [<jats:styled-content style=\"fixed-case\">HbA<jats:sub>1c<\/jats:sub><\/jats:styled-content>], fasting plasma glucose [<jats:styled-content style=\"fixed-case\">FPG<\/jats:styled-content>] and urinary glucose excretion). Two studies (<jats:italic>n<\/jats:italic> = 748, 12 weeks) were used to evaluate tolerability <jats:styled-content style=\"fixed-case\">E\u2212R<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The efficacy model predicted maximal decreases in <jats:styled-content style=\"fixed-case\">FPG<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">HbA<jats:sub>1c<\/jats:sub><\/jats:styled-content> of 16% and 0.6%, respectively, assuming a baseline <jats:styled-content style=\"fixed-case\">FPG<\/jats:styled-content> concentration of 8\u2009m<jats:sc>m<\/jats:sc> (144\u2009mg\u2009dl<jats:sup>\u22121<\/jats:sup>) and 10\u201325\u2009mg every day empagliflozin targeted 80\u201390% of these maximums. Increases in exposure had no effect on incidence rates of hypoglycaemia (<jats:italic>n<\/jats:italic> = 4), urinary tract infection (<jats:italic>n<\/jats:italic> = 17) or genital\/vulvovaginal\u2010related (<jats:italic>n<\/jats:italic> = 16) events, although low prevalence rates may have precluded more accurate evaluation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">E\u2212R<\/jats:styled-content> analyses indicated that 10 and 25\u2009mg once daily empagliflozin doses achieved near maximal glucose lowering efficacy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12453","type":"journal-article","created":{"date-parts":[[2014,6,26]],"date-time":"2014-06-26T10:24:30Z","timestamp":1403778270000},"page":"1407-1418","source":"Crossref","is-referenced-by-count":16,"title":["Exposure\u2212response modelling for empagliflozin, a sodium glucose cotransporter 2 (<scp>SGLT2<\/scp>) inhibitor, in patients with type 2 diabetes"],"prefix":"10.1111","volume":"78","author":[{"given":"Matthew M.","family":"Riggs","sequence":"first","affiliation":[{"name":"Metrum Research Group LLC  Tariffville CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo J.","family":"Seman","sequence":"additional","affiliation":[{"name":"US Medical Affairs Boehringer Ingelheim Pharmaceuticals, Inc.  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