{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T02:42:05Z","timestamp":1775011325569,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2015,8,20]],"date-time":"2015-08-20T00:00:00Z","timestamp":1440028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007013","name":"F. Hoffman-La Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      To assess the efficacy, safety and tolerability of different doses of tofogliflozin, a novel, highly selective sodium\u2010glucose cotransporter 2 (\n                      <jats:styled-content style=\"fixed-case\">SGLT2<\/jats:styled-content>\n                      ) inhibitor, in patients with type 2 diabetes mellitus (\n                      <jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a 12\u2010week, multicentre, multinational, randomized, double\u2010blind, parallel\u2010group, placebo\u2010controlled, dose\u2010finding study, patients with inadequate glycaemic control from diet and exercise alone, or from diet and exercise plus a stable dose of metformin, were randomized to one of five doses of tofogliflozin (2.5, 5, 10, 20, or 40\u2009mg) or placebo. The primary efficacy endpoint was absolute change at week 12 from baseline in glycated haemoglobin (\n                      <jats:styled-content style=\"fixed-case\">HbA1c<\/jats:styled-content>\n                      ), minus the change in the placebo group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Statistically significant dose\u2010dependent reductions in\n                      <jats:styled-content style=\"fixed-case\">HbA1c<\/jats:styled-content>\n                      were shown in all treated groups except the 2.5\u2010mg dose group, with a maximum reduction of 0.56% (placebo\u2010subtracted) at the 40\u2010mg dose, along with increased urinary glucose excretion. Metformin treatment had no substantial influence on tofogliflozin efficacy. Dose\u2010dependent reductions in fasting plasma glucose and body weight were observed, and glucose intolerance was improved, with a trend towards blood pressure reduction. Slight increases were observed for mean ketone bodies with no abnormal change in ketone body ratio. No deaths or treatment\u2010related serious adverse events were reported. The incidence of adverse events was similar in the placebo (37.9%) to that in the tofogliflozin group (35.9\u201346.3%). Withdrawal because of adverse events was rare (\u22642 patients per treatment group), with similar rates of withdrawal in the placebo and tofogliflozin groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      A once\u2010daily dose of tofogliflozin for 12\u2009weeks was an effective, safe and well\u2010tolerated treatment for\n                      <jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.12538","type":"journal-article","created":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T11:02:30Z","timestamp":1436871750000},"page":"984-993","source":"Crossref","is-referenced-by-count":65,"title":["A novel and selective sodium\u2010glucose cotransporter\u20102 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus"],"prefix":"10.1111","volume":"17","author":[{"given":"S.","family":"Ikeda","sequence":"first","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Takano","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O.","family":"Cynshi","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Co., Ltd  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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