{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T03:12:56Z","timestamp":1789096376385,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,6,5]],"date-time":"2018-06-05T00:00:00Z","timestamp":1528156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Boehringer Ingelheim Eli Lilly and Company"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      This phase 2, double\u2010blind, randomized, placebo\u2010controlled trial (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      NCT02702011) with 4 sites in Japan investigated the pharmacodynamics (PD), pharmacokinetics (PK) and safety profile of empagliflozin in Japanese participants with type 1 diabetes mellitus (T1DM) as adjunctive therapy to insulin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Participants using multiple daily injections of insulin for \u226512 months, with HbA1c of 7.5%\u201010.0%, entered a 2\u2010week, open\u2010label, placebo run\u2010in period, followed by a 4\u2010week, double\u2010blind period during which participants were randomized 1:1:1:1 to receive empagliflozin 2.5 mg (n = 13), empagliflozin 10 mg (n = 12), empagliflozin 25 mg (n = 12) or placebo (n = 11). The primary objective was to assess the effect of empagliflozin vs placebo on urinary glucose excretion (UGE) after 7 days of treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PD: Empagliflozin resulted in a dose\u2010dependent significant increase in 24\u2010hour UGE compared with placebo (UGE placebo\u2010corrected mean [95% confidence interval] change from baseline: 2.5 mg, 65.10 [43.29, 86.90] g\/24 h; 10 mg, 81.19 [58.80, 103.58] g\/24 h; 25 mg, 98.11 [75.91, 120.31] g\/24 h). After 4 weeks of treatment, UGE increase was associated with improved glycaemic control, reduced body weight and decreased insulin needs. Empagliflozin treatment also resulted in dose\u2010dependent increases in serum ketone bodies and free fatty acids. PK: Plasma empagliflozin levels increased in a dose\u2010dependent manner and peaked at 1.5 hours. In this short study, empagliflozin was well tolerated, with no increase in rate of hypoglycaemia and no diabetic ketoacidosis events reported.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Based on this short\u2010duration phase 2 study, the PK\/PD profile of empagliflozin in Japanese participants with T1DM is comparable to that of non\u2010Japanese participants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13351","type":"journal-article","created":{"date-parts":[[2018,5,15]],"date-time":"2018-05-15T22:22:04Z","timestamp":1526422924000},"page":"2190-2199","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Empagliflozin as adjunct to insulin in Japanese participants with type 1 diabetes: Results of a 4\u2010week, double\u2010blind, randomized, placebo\u2010controlled phase 2 trial"],"prefix":"10.1111","volume":"20","author":[{"given":"Akira","family":"Shimada","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Diabetes Saitama Medical University  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Hanafusa","sequence":"additional","affiliation":[{"name":"Sakai City Medical Center  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsutaka","family":"Yasui","sequence":"additional","affiliation":[{"name":"Nippon Boehringer Ingelheim Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganghyuck","family":"Lee","sequence":"additional","affiliation":[{"name":"Nippon Boehringer Ingelheim Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Taneda","sequence":"additional","affiliation":[{"name":"Nippon Boehringer Ingelheim Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Sarashina","sequence":"additional","affiliation":[{"name":"Nippon Boehringer Ingelheim Co., Ltd.  Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Shiki","sequence":"additional","affiliation":[{"name":"Nippon Boehringer Ingelheim Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyothis","family":"George","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH  Ingelheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nima","family":"Soleymanlou","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Canada  Burlington Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Marquard","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH  Ingelheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,5]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"American Diabetes Association.Standards of medical care in diabetes 2017.https:\/\/professional.diabetes.org\/sites\/professional.diabetes.org\/files\/media\/dc_40_s1_final.pdf. 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