{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:48:14Z","timestamp":1787014094461,"version":"build-2736575974"},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T00:00:00Z","timestamp":1545350400000},"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":[[2019,4]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To assess the pharmacokinetics\/pharmacodynamics (PK\/PD) of dapagliflozin, a sodium\u2010glucose co\u2010transporter 2 inhibitor that increases urinary glucose excretion (UGE) and its major metabolite, dapagliflozin\u20103\u2010O\u2010glucuronide (D3OG), in Japanese patients with type 1 diabetes (T1D) and inadequate glycaemic control (HbA1c 7%\u201010%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Japanese patients (18\u201065\u2009years) with inadequately controlled T1D were randomized 1:1:1 to dapagliflozin 5 mg, 10 mg or placebo (n\u2009=\u200914 each) once daily for 7 days, with adjustable insulin. The PK\/PD characteristics of dapagliflozin and D3OG were assessed on Day 7. Patients underwent follow\u2010up evaluation on Days 8 and 14. Adverse events (AEs), hypoglycaemic episodes and events of diabetic ketoacidosis (DKA) were recorded over the treatment and follow\u2010up periods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 42 randomized patients received dapagliflozin or placebo. PK variables increased in a dose\u2010dependent manner. D3OG was generated rapidly, with a median time to maximum plasma concentration of 2.0 hours (1.0\u20103.0). The dapagliflozin dose\u2010UGE relationship was attenuated, with larger insulin dose reductions than anticipated. Mean percent (standard error) changes in total daily insulin dose from baseline to Day 7 were\u2009\u2212\u200936.86% (3.32), \u221239.13% (2.68) and\u2009\u2212\u20094.97% (5.28) for dapagliflozin 5 mg and 10 mg and for placebo, respectively. No DKA was reported. AEs were consistent with the established dapagliflozin safety profile. There was no increase in hypoglycaemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The PK and safety profiles of dapagliflozin in Japanese patients with T1D were consistent with previous studies, but with an unanticipated attenuation of the PD dose\u2010response measured as UGE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13593","type":"journal-article","created":{"date-parts":[[2018,11,30]],"date-time":"2018-11-30T03:24:22Z","timestamp":1543548262000},"page":"876-882","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Pharmacokinetics and pharmacodynamics of dapagliflozin in combination with insulin in Japanese patients with type 1 diabetes"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5961-1816","authenticated-orcid":false,"given":"Hirotaka","family":"Watada","sequence":"first","affiliation":[{"name":"Department of Metabolism and Endocrinology Juntendo University Graduate School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanari","family":"Shiramoto","sequence":"additional","affiliation":[{"name":"SOUSEIKAI Hakata Clinic  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Ueda","sequence":"additional","affiliation":[{"name":"AstraZeneca  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8261-8116","authenticated-orcid":false,"given":"Weifeng","family":"Tang","sequence":"additional","affiliation":[{"name":"AstraZeneca  Gaithersburg Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Asano","sequence":"additional","affiliation":[{"name":"AstraZeneca  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Thor\u00e9n","sequence":"additional","affiliation":[{"name":"AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyosung","family":"Kim","sequence":"additional","affiliation":[{"name":"AstraZeneca  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshitaka","family":"Yajima","sequence":"additional","affiliation":[{"name":"AstraZeneca  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Boulton","sequence":"additional","affiliation":[{"name":"AstraZeneca  Gaithersburg Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichi","family":"Araki","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine Kumamoto University  Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12600"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.077487"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2017.10.004"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-0090"},{"key":"e_1_2_7_6_1","first-page":"62","article-title":"Glycemic targets in diabetes care: emerging clarity after accord","volume":"126","author":"Buse JB","year":"2015","journal-title":"Trans Am Clin Climatol Assoc."},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3180"},{"key":"e_1_2_7_8_1","unstructured":"AstraZeneca. Forxiga\u00ae receives regulatory approval in Japan for the treatment of type 2 diabetes.2014.https:\/\/www.astrazeneca.com\/media\u2010centre\/press\u2010releases\/2014\/forxiga\u2010approval\u2010japan\u2010type\u20102\u2010diabetes\u2010treatment\u201024032014.html#!Accessed"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-2955"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30308-X"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-0623"},{"key":"e_1_2_7_12_1","first-page":"dc181087","article-title":"Efficacy and safety of dapagliflozin in patients with inadequately controlled Type 1 diabetes: the DEPICT\u20101 52\u2010Week Study","volume":"23","author":"Dandona P","year":"2018","journal-title":"Diabetes Care."},{"issue":"10","key":"e_1_2_7_13_1","first-page":"1","article-title":"Racial and ethnic differences in response to medicines: towards individualized pharmaceutical treatment","volume":"94","author":"Burroughs VJ","year":"2002","journal-title":"J Natl Med Assoc."},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2008.12.034"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01359.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","unstructured":"SovolovV YakovlevaT UedaS et al. Dapagliflozin exposure response in Japanese vs. Non\u2010Japanese patients with Type 1 diabetes. American Diabetes Association 78th Scientific Sessions;2018;67(suppl 1):1174P; Orlando Florida.","DOI":"10.2337\/db18-1174-P"},{"key":"e_1_2_7_17_1","unstructured":"UchigataY TO FujiiH OhashiH et al. The safety and efficacy of long term (52\u2009weeks) dapagliflozin therapy in Japanese subjects with type 1 diabetes. Paper presented at: 61st Annual Meeting of the Japan Diabetes Society; May 24\u201326 2018; Tokyo Japan."},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000000581"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.13593","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.13593","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.13593","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.13593","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T23:40:44Z","timestamp":1761867644000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.13593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,21]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1111\/dom.13593"],"URL":"https:\/\/doi.org\/10.1111\/dom.13593","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,21]]},"assertion":[{"value":"2018-08-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}