{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T15:09:38Z","timestamp":1778944178356,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,2,11]],"date-time":"2018-02-11T00:00:00Z","timestamp":1518307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To evaluate the long\u2010term safety and efficacy of tofogliflozin as an add\u2010on treatment to insulin over 52 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>This 52\u2010week, multicentre, Phase 4 study consisted of a 16\u2010week, randomized, double\u2010blind, placebo\u2010controlled phase and a 36\u2010week open label extension phase (NCT02201004). Japanese patients with type 2 diabetes mellitus, aged 20 to 75 years, with suboptimal glycaemic control (7.5%\u201010.5%) receiving insulin monotherapy (basal\u2010bolus, bolus, premix [low and high] and basal) or receiving combination therapy with basal insulin and dipeptidyl peptidase\u20104 inhibitor were eligible for participation. Patients who received tofogliflozin throughout the study (52 weeks) were referred to as the \u2018tofo\u2010tofo group\u2019 and patients who received placebo and tofogliflozin (36 weeks) were referred to as the \u2018pla\u2010tofo group\u2019.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 210 patients received treatment per randomization. Hypoglycaemia was the most common treatment\u2010emergent adverse event (AE) (42.9% in the tofo\u2010tofo group and 29.4% in the pla\u2010tofo group). Patients reported genital infection, urinary tract infection, excessive urination and AEs related to volume depletion (2.1%, 2.1%, 7.1% and 10.0% of patients in the tofo\u2010tofo group, and 0%, 1.5%, 2.9% and 7.4% of patients in the pla\u2010tofo group, respectively). Mean HbA1c and body weight at baseline (mean changes \u00b1 standard error from baseline to Week 52) in the tofo\u2010tofo and pla\u2010tofo groups were 8.53% (\u22120.76% \u00b1 0.077) and 8.40% (\u22120.73% \u00b1 0.102); 68.84 kg (\u22121.52 kg \u00b1 0.207) and 72.24 kg (\u22122.13 kg \u00b1 0.313), respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrates the safety and efficacy of tofogliflozin as add\u2010on to insulin therapy in type 2 diabetes mellitus patients, offering a new therapeutic solution to diabetes management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13213","type":"journal-article","created":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T21:22:07Z","timestamp":1515532927000},"page":"1176-1185","source":"Crossref","is-referenced-by-count":20,"title":["Long\u2010term safety and efficacy of tofogliflozin as add\u2010on to insulin in patients with type 2 diabetes: Results from a 52\u2010week, multicentre, randomized, double\u2010blind, open\u2010label extension, Phase 4 study in Japan (J\u2010STEP\/INS)"],"prefix":"10.1111","volume":"20","author":[{"given":"Yasuo","family":"Terauchi","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Yokohama City University School of Medicine  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Tamura","sequence":"additional","affiliation":[{"name":"Real World Evidence Data Generation, Medical Affairs Sanofi K.K.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Senda","sequence":"additional","affiliation":[{"name":"Real World Evidence Data Generation, Medical Affairs Sanofi K.K.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoji","family":"Gunji","sequence":"additional","affiliation":[{"name":"Post Marketing Surveillance Department Kowa Company, Ltd.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1574-0565","authenticated-orcid":false,"given":"Kohei","family":"Kaku","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine 1 Kawasaki Medical School  Kurashiki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,2,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.191593"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-014-0229-1"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2014.887680"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12538"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.25.12.2133"},{"key":"e_1_2_7_7_1","article-title":"Efficacy and safety of sitagliptin added to insulin in Japanese patients with type 2 diabetes: the EDIT randomized trial","volume":"10","author":"Sato S","year":"2015","journal-title":"PLoS One"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-S010"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12957"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01511.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-3055"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-1237"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12853"},{"key":"e_1_2_7_14_1","first-page":"313","article-title":"Clinical potential of sodium\u2010glucose cotransporter 2 inhibitors in the management of type 2 diabetes","volume":"5","author":"Kim Y","year":"2012","journal-title":"Diabetes Metab Syndr Obes"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-016-0407-4"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12745"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1251"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13124"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.2924"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_2_7_22_1","unstructured":"Food and Drug Administration. FDA drug safety communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood. 2015. Available athttps:\/\/www.fda.gov\/downloads\/Drugs\/DrugSafety\/UCM446954.pdf. Accessed December 4 2017."},{"key":"e_1_2_7_23_1","unstructured":"Food and Drug Administration. FDA drug safety communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. 2015. Available athttps:\/\/www.fda.gov\/downloads\/Drugs\/DrugSafety\/UCM475487.pdf. Accessed December 4 2017."},{"key":"e_1_2_7_24_1","unstructured":"Food and Drug Administration. FDA drug safety communication: FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana Invokamet Invokamet XR). 2017. Available athttps:\/\/www.fda.gov\/downloads\/Drugs\/DrugSafety\/UCM558427.pdf. 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