{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:41:29Z","timestamp":1792384889987,"version":"4.4.0"},"reference-count":27,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006453","name":"Taisho Toyama Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006453","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":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Type 2 diabetes drives the progression of metabolic dysfunction\u2010associated steatohepatitis (MASH). We evaluated whether antidiabetic therapy, specifically adding sodium\u2013glucose cotransporter 2 (SGLT2) inhibitor to a glucagon\u2010like peptide\u20101 receptor agonist (GLP\u20101RA), improves liver histology in adults with biopsy\u2010proven MASH and type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>In this 52\u2010week, open\u2010label, randomised, parallel\u2010group trial in Japan, adults with biopsy\u2010confirmed MASH and type 2 diabetes received semaglutide plus luseogliflozin or semaglutide alone at antidiabetic doses. Paired liver biopsies at baseline and Week 52 were evaluated by blinded pathologists. Primary histological endpoints included resolution of MASH without worsening fibrosis, \u2265\u20091\u2010point improvement in the non\u2010alcoholic fatty liver disease (NAFLD) activity score without worsening fibrosis and \u2265\u20091\u2010stage improvement in fibrosis without worsening MASH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sixty participants were randomised (combination,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200924; monotherapy,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200936). At Week 52, all histological endpoints numerically favoured combination therapy. Resolution of MASH without worsening fibrosis occurred in 34.9% versus 19.4%, \u2265\u20091\u2010point improvement in the NAFLD activity score (NAS) in 75.5% versus 55.6% and \u2265\u20091\u2010stage fibrosis improvement in 26.9% versus 13.9%. In the pre\u2010specified per\u2010protocol analysis, \u2265\u20091\u2010point improvement in the NAS was nominally significant. Combination therapy reduced body weight, glycated haemoglobin levels, aminotransferase levels and FibroScan\u2010derived liver stiffness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In the pre\u2010specified full analysis set, combination therapy at antidiabetic doses did not significantly improve pre\u2010specified histological endpoints compared with monotherapy. In the pre\u2010specified per\u2010protocol analysis, a nominal improvement in the NAS was observed. Combination therapy improved body weight, glycemic control, aminotransferase levels and liver stiffness, with no new safety concerns identified.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      UMIN Clinical Trials Registry (UMIN\u2010CTR): UMIN000045003; Japan Registry of Clinical Trials (jRCT): jRCTs061210009\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71233","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:49:23Z","timestamp":1786952963000},"page":"10163-10172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of Luseogliflozin Added to Semaglutide in Patients With Metabolic Dysfunction\u2010Associated Steatohepatitis and Type 2 Diabetes Mellitus: A Randomised, Open\u2010Label Trial"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9905-5356","authenticated-orcid":false,"given":"Teruki","family":"Miyake","sequence":"first","affiliation":[{"name":"Department of Lifestyle\u2010Related Medicine and Endocrinology Ehime University Graduate School of Medicine  Toon Ehime Japan"},{"name":"Total Medical Support Center Ehime University Hospital  Toon Ehime Japan"},{"name":"Center for Data Science Ehime University  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5015-0045","authenticated-orcid":false,"given":"Osamu","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Health Service Center Ehime University  Matsuyama Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Hirooka","sequence":"additional","affiliation":[{"name":"Total Medical Support Center Ehime University Hospital  Toon Ehime Japan"},{"name":"Center for Data Science Ehime University  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Community and General Medicine Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Tokumoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Kanamoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Okazaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Yukimoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Takeshita","sequence":"additional","affiliation":[{"name":"Department of Inflammatory Bowel Diseases and Therapeutics Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teru","family":"Kumagi","sequence":"additional","affiliation":[{"name":"Post Graduate Medical Education Center Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichi","family":"Hiasa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology Ehime University Graduate School of Medicine  Toon Ehime 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https:\/\/www.fda.gov\/drugs\/news\u2010events\u2010human\u2010drugs\/fda\u2010approves\u2010treatment\u2010serious\u2010liver\u2010disease\u2010known\u2010mash."},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-022-01239-7"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20701"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.70256"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-024-02122-x"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-024-02158-z"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14319"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-62891-8"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc21-1953"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42000\u2010025\u201000743\u20102"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607141"}],"container-title":["Diabetes, 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