{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:13:57Z","timestamp":1785251637973,"version":"3.55.0"},"reference-count":48,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"unspecified","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Kowa Co. Ltd","award":["2017115"],"award-info":[{"award-number":["2017115"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Diab Res Care"],"accepted":{"date-parts":[[2021,1,24]]},"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>The treatment of diabetes has a significant impact on the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We compared the effectiveness of tofogliflozin, a selective sodium-glucose cotransporter 2 inhibitor, and pioglitazone for the treatment of NAFLD patients with type 2 diabetes mellitus.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Research design and methods<\/jats:title>\n                  <jats:p>This open-label, prospective, single-center, randomized clinical trial recruited NAFLD patients with type 2 diabetes mellitus and a hepatic fat fraction of at least 10% as assessed based on the MRI-proton density fat fraction (MRI-PDFF). Eligible patients were stratified according to hemoglobin A1c (HbA1c), alanine transaminase, and MRI-PDFF levels and randomly assigned (1:1) to receive either 20\u2009mg tofogliflozin or 15\u201330\u2009mg pioglitazone, orally, once daily for 24 weeks. The primary endpoint was an absolute change in MRI-PDFF at 24 weeks. Efficacy and safety was assessed in all treated patients. This trial was registered in the Japan Registry of Clinical Trials.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Overall, 40 eligible patients were randomly assigned to receive tofogliflozin (n=21) or pioglitazone (n=19). Changes in hepatic steatosis after 24 weeks of treatment were evaluated by MRI-PDFF, which showed a significant decrease in both groups (\u22127.54% (p&lt;0.0001) and \u22124.12% (p=0.0042) in the pioglitazone and tofogliflozin groups, respectively). Compared with baseline, the body weight decreased by 2.83\u00b12.86\u2009kg (\u22123.6%, p=0.0443) in the tofogliflozin group and increased by 1.39\u00b12.62\u2009kg (1.7%, p=0.0002) in the pioglitazone group after 24 weeks. No life-threatening events or treatment-related deaths occurred.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Tofogliflozin was well tolerated, and it reduced the MRI-PDFF levels in NAFLD patients with type 2 diabetes mellitus.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>jRCTs031180159.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjdrc-2020-001990","type":"journal-article","created":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T16:25:39Z","timestamp":1613492739000},"page":"e001990","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":94,"title":["Comparing the effects of tofogliflozin and pioglitazone in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus (ToPiND study): a randomized prospective open-label controlled trial"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7815-549X","authenticated-orcid":false,"given":"Masato","family":"Yoneda","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaomi","family":"Kessoku","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Yokohama City 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