{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:40:44Z","timestamp":1786977644258,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:00:00Z","timestamp":1700438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp;amp; Metabol"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>How the pathology of type 2 diabetes (T2D), including hyperglycaemia and obesity, affects liver enzymes has not been clinically demonstrated. Thus, we compared time courses of gamma\u2010glutamyltransferase (GGT) and alanine aminotransferase (ALT) with those of fasting plasma glucose (FPG) and body weight (BW) during treatment with the SGLT2 inhibitor tofogliflozin for T2D.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We post\u2010hoc\u00a0analysed preexisting data on 1046 people with T2D administered tofogliflozin or placebo for 24\u2009weeks in four tofogliflozin studies. First, time courses of percent changes in variables during the intervention were analysed using a mixed effect model to explore the similarity of the time courses and to evaluate time\u2010treatment interactions. Second, clinical factors related to the percent changes in GGT and ALT were clarified using multivariate analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      GGT levels and FPG values rapidly and significantly decreased via tofogliflozin as early as week 4, with decreases maintained until week 24. Conversely, BW and ALT decreased progressively until week 24. Time courses of FPG (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.365, time\u2010treatment interaction) and GGT (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.510) reductions were parallel between tofogliflozin and placebo from weeks 4 to 24, while BW and ALT reductions (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001, respectively) were not. Reductions in GGT at week 24 were associated with reductions in FPG and BW at week 24, whereas ALT reductions were only associated with reductions in BW.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Reductions in GGT and ALT were associated with the anti\u2010hyperglycaemic and anti\u2010obesity effects of tofogliflozin, respectively, in people with T2D. Therefore, GGT and ALT may be surrogate markers for hyperglycaemia and obesity in T2D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.461","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T18:11:06Z","timestamp":1700590266000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Reductions in liver enzymes are associated with anti\u2010hyperglycaemic and anti\u2010obesity effects of tofogliflozin in people with type 2 diabetes: Post\u2010hoc analyses"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4393-3244","authenticated-orcid":false,"given":"Toshinari","family":"Takamura","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Kanazawa University Graduate School of Medical Sciences  Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1574-0565","authenticated-orcid":false,"given":"Kohei","family":"Kaku","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Kawasaki Medical School  Kurashiki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Kowa Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Kusakabe","sequence":"additional","affiliation":[{"name":"Kowa Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Hygiene and Public Health , Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University  Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9130-0137","authenticated-orcid":false,"given":"Hideki","family":"Suganami","sequence":"additional","affiliation":[{"name":"Clinical Data Science Department Kowa Co., Ltd.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ12-0228"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2016.01.001"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.06.002"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-0148"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.3.701"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.10.2623"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.11.2855"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-1870"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.6.1889"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2007.218"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.890"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2010-0029"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-159-4-201308200-00007"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-13-65"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105319"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2014.887680"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-0662-0209"},{"issue":"2","key":"e_1_2_10_19_1","first-page":"L102","article-title":"Protection of alveolar macrophages from hyperoxia by gamma\u2010glutamyl transpeptidase","volume":"259","author":"Forman HJ","year":"1990","journal-title":"Am J Physiol"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.11.5.7946387"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004352200"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715760410001694026"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/818570"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.35.4.426"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.06117"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00610-4"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/8490643"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.1040752"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-10-454"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23276"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.04.005"}],"container-title":["Endocrinology, Diabetes &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/edm2.461","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T01:56:07Z","timestamp":1706147767000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/edm2.461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,20]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/edm2.461"],"URL":"https:\/\/doi.org\/10.1002\/edm2.461","archive":["Portico"],"relation":{},"ISSN":["2398-9238","2398-9238"],"issn-type":[{"value":"2398-9238","type":"print"},{"value":"2398-9238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,20]]},"assertion":[{"value":"2023-06-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e461"}}