{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:48:17Z","timestamp":1787014097642,"version":"build-2736575974"},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,12,16]],"date-time":"2018-12-16T00:00:00Z","timestamp":1544918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To assess the dapagliflozin exposure\u2010response relationship in Japanese and non\u2010Japanese patients with type 1 diabetes mellitus (T1DM) and investigate if a dose adjustment is required in Japanese patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Data from two clinical studies were used to develop a non\u2010linear mixed effects model describing the relationship between dapagliflozin exposure (area under the concentration curve) and response (24\u2010hour urinary glucose excretion [UGE]) in Japanese and non\u2010Japanese patients with T1DM. The effects of patient\u2010level characteristics (covariates; identified using a stepwise procedure) on response was also assessed. Simulations were performed using median\u2010normalized covariate values.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Data from 84 patients were included. Average self\u2010monitored blood glucose (SMBG) at day 7, change from baseline in total insulin dose at day 7, and baseline estimated glomerular filtration rate (eGFR) all had a significant effect on 24\u2010hours UGE, with SMBG being the most influential. Dapagliflozin systemic exposure for matching doses and baseline eGFR was similar between Japanese and non\u2010Japanese patients; however, higher SMBG and a greater reduction in total insulin dose was observed in the Japanese population. When the significant covariates were included, the model fit the data well for both populations, and accurately predicted exposure\u2010response in the Japanese and non\u2010Japanese populations, in agreement with the observed data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>There was no difference in dapagliflozin exposure\u2010response in Japanese and non\u2010Japanese patients with T1DM once differences in renal function, glycaemic control and insulin dose reductions between studies were considered. Therefore, no dose adjustment is recommended in Japanese patients with T1DM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13586","type":"journal-article","created":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T02:39:26Z","timestamp":1542681566000},"page":"829-836","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Urinary glucose excretion after dapagliflozin treatment: An exposure\u2010response modelling comparison between Japanese and non\u2010Japanese patients diagnosed with type 1 diabetes mellitus"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7066-0811","authenticated-orcid":false,"given":"Victor","family":"Sokolov","sequence":"first","affiliation":[{"name":"M&amp;S Decisions  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9715-0931","authenticated-orcid":false,"given":"Tatiana","family":"Yakovleva","sequence":"additional","affiliation":[{"name":"M&amp;S Decisions  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0356-5555","authenticated-orcid":false,"given":"Shinya","family":"Ueda","sequence":"additional","affiliation":[{"name":"GMD, R&amp;D Japan AstraZeneca  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4492-5243","authenticated-orcid":false,"given":"Joanna","family":"Parkinson","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca  Gothenburg 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