{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:54:10Z","timestamp":1789419250920,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008349","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","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":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The precise mechanism of sodium glucose co\u2010transporter 2 (SGLT2) inhibitor on reno\u2010protective effect has been still unclear. In this study, we hypothesised that SGLT2 inhibitor prevents diabetic kidney disease via reduction of hypoxia\u2010induced factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      In this multicenter, prospective, randomised, double blinded clinical trial, people with type 2 diabetes and microalbuminuria were randomised equally to empagliflozin (10\u2009mg\/day) (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200940) and placebo (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200939) and followed 24\u2009weeks. The primary endpoint was change in urinary albumin creatinine ratio (ACR) and urinary liver type fatty acid binding protein (L\u2010FABP) excretion from baseline to 24\u2009weeks. Major secondary outcome was change in serum vascular endothelial growth factor (VEGF), angiopoietin\u2010like proteins 2 (ANGPTL2), angiopoietin\u2010like proteins 4 (ANGPTL4), and adrenomedullin (AM) levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Although the reduction of ACR was significantly greater in the empagliflozin group than the placebo group at 4 and 12\u2009weeks, the difference of change at 24\u2009weeks between the two groups was not statistically significant (Empagliflozin group\u2014Placebo group: \u22120.3643, 95% CI: \u22120.7571 to 0.0285,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0686). There was no difference in urinary L\u2010FABP excretion between the empagliflozin and placebo groups. Serum VEGF and ANGPTL2 decreased significantly more in the empagliflozin group, whereas there were no significant differences in AM and ANGPTL4.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results demonstrated that empagliflozin partially suppressed the hypoxia\u2010induced angiogenic factors overproduction in addition to a declining trend in ACR in the early stage of diabetic kidney disease, which might contribute to the mechanisms of reno\u2010protective effects of this agent (jRCTs051200147).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70485","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T08:29:07Z","timestamp":1769416147000},"page":"2978-2987","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of empagliflozin on urinary albumin excretion and hypoxic biomarkers in early diabetic kidney disease: A randomised double\u2010blind, placebo\u2010controlled trial"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9953-3736","authenticated-orcid":false,"given":"Hisashi","family":"Makino","sequence":"first","affiliation":[{"name":"Division of Diabetes and Lipid Metabolism National Cerebral and Cardiovascular Center  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Kasahara","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Translational Science, Nara Medical University Hospital  Kashihara Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuzo","family":"Takashima","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Translational Science, Nara Medical University Hospital  Kashihara Nara 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