{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T19:41:39Z","timestamp":1769197299719,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T00:00:00Z","timestamp":1552521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/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":[[2019,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To quantitatively describe the relationship between dapagliflozin systemic exposure and HbA1c response among patients with type 1 diabetes mellitus (T1DM) and assess the potential impact of covariate effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Individual longitudinal HbA1c data from two phase 3 studies in patients with T1DM (24\u2010week treatment with once\u2010daily dapagliflozin 5 or 10\u2009mg or placebo, with adjustable insulin) were analyzed using a non\u2010linear mixed effect modeling approach. Area under the concentration curve was used to measure dapagliflozin systemic exposure. Baseline HbA1c, estimated glomerular filtration rate, reduction in total insulin dose, baseline glucose concentrations, age, sex, race (Asian vs. non\u2010Asian), and insulin administration method (multiple daily injections vs. insulin pump) were assessed as covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A maximum effect (E\n                      <jats:sub>max<\/jats:sub>\n                      ) model identified a positive exposure\u2013response relationship. Model\u2010predicted placebo\u2010corrected HbA1c reductions after 24\u2009weeks for dapagliflozin 5\u2010 and 10\u2010mg doses were\u2009\u2212\u20090.42% [95% confidence interval (CI) \u22120.47 to \u22120.36) and\u2009\u2212\u20090.45% (95% CI \u22120.50 to \u22120.40), respectively; baseline HbA1c was ~8.4%. This was in good agreement with actual observations from both studies. Baseline HbA1c was a significant covariate: patients with higher baseline HbA1c were predicted to have greater HbA1c reductions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The relationship between dapagliflozin systemic exposure and HbA1c response was successfully described in patients with T1DM. None of the tested covariates affected the efficacy of dapagliflozin to a clinically relevant extent. Therefore, no dose adjustment of dapagliflozin is required in patients with T1DM based on the tested covariates.\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      , NCT02268214; NCT02460978.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13664","type":"journal-article","created":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T03:47:41Z","timestamp":1550029661000},"page":"1381-1387","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Model\u2010based characterization of the relationship between dapagliflozin systemic exposure and HbA1c response in patients with type 1 diabetes mellitus"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4492-5243","authenticated-orcid":false,"given":"Joanna","family":"Parkinson","sequence":"first","affiliation":[{"name":"Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8261-8116","authenticated-orcid":false,"given":"Weifeng","family":"Tang","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca  Gaithersburg Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magnus","family":"\u00c5strand","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Melin","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ella","family":"Ekholm","sequence":"additional","affiliation":[{"name":"Global Medicines Development IMED Biotech Unit, AstraZeneca  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bengt","family":"Hamr\u00e9n","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca  Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Boulton","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology, Early Clinical Development IMED Biotech Unit, AstraZeneca  Gaithersburg Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-Sint01"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2006.00686.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2009.02296.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-1140"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13124"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep44128"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP151113.CO"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2005.10.009"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP13065.OR"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP12100.OR"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30308-X"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-2955"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2014.909407"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.021887"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.029190"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.03.009"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-159-4-201308200-00007"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-0623"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12594"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.71"},{"key":"e_1_2_8_22_1","unstructured":"MelinJ ParkinsonJR RekicD et al.Dapagliflozin pharmacokinetics is similar in adults with type 1 and type 2 diabetes mellitus. Population approach group in Europe Montreux Switzerland.2018. Abstr 8427.https:\/\/www.page-meeting.org\/?abstract=8427. 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