{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T17:34:36Z","timestamp":1774114476448,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T00:00:00Z","timestamp":1666483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012351","name":"Mitsubishi Tanabe Pharma Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012351","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":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate factors associated with proteinuria regression in patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>This study was a post hoc analysis of the CANDLE trial (UMIN000017669), which compared the effect of 24\u2009weeks of treatment with canagliflozin or glimepiride for changes in N\u2010terminal pro\u2010brain natriuretic peptide in patients with T2DM and chronic heart failure (CHF). Factors associated with regression of proteinuria at 24\u2009weeks were evaluated with multivariate logistic models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The rate of regression of proteinuria was higher (28\/102, 27.5% vs. 12\/112, 10.7%), and that of progression was lower (9\/102, 8.8% vs. 26\/112, 23.2%), in the canagliflozin versus the glimepiride group (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.0001). There were no differences in the change in the estimated glomerular filtration rate category between groups. Insulin level, homeostatic model assessment of \u03b2\u2010cell function, homeostatic model assessment for insulin resistance and estimated plasma volume were decreased at 24\u2009weeks in the regression subclass but not in the progression subclass, suggesting that regression of proteinuria is associated with the declines in these values in the canagliflozin group. Higher insulin level at baseline was solely associated with proteinuria regression in the multivariate logistic regression model (baseline insulin, as per a 1\u2010mlU\/L increase, odds ratio 1.24 [1.05\u20101.47],\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u2009.011).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with T2DM and CHF, regression of proteinuria with canagliflozin treatment was associated with the pretreatment insulin level. These results may provide clinicians with novel mechanistic insights into the beneficial effects of canagliflozin on renal outcomes and may warrant discussion for selecting preferred patient profiles, including pretreatment insulin levels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14876","type":"journal-article","created":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T06:18:56Z","timestamp":1664864336000},"page":"354-364","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Canagliflozin reduces proteinuria by targeting hyperinsulinaemia in diabetes patients with heart failure: A post hoc analysis of the\n                    <scp>CANDLE<\/scp>\n                    trial"],"prefix":"10.1111","volume":"25","author":[{"given":"Satoshi","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Department of Diabetes, Endocrinology, and Metabolism Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7835-7665","authenticated-orcid":false,"given":"Michio","family":"Shimabukuro","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology, and Metabolism Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3352-7661","authenticated-orcid":false,"given":"Atsushi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Saga University  Saga Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takumi","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics Osaka Metropolitan University Graduate School of Medicine  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinya","family":"Hiramitsu","sequence":"additional","affiliation":[{"name":"Hiramitsu Heart Clinic  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naohiko","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Clinical Examination Oita University Faculty of Medicine  Yufu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiaki","family":"Kadokami","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Fukuoka Saiseikai Futsukaichi Hospital  Chikushino Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayoshi","family":"Ajioka","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Internal Medicine Tosei General Hospital  Seto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Cardiology Yokohama Minami Kyosai Hospital  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2534-0939","authenticated-orcid":false,"given":"Koichi","family":"Node","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Saga University  Saga Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the CANDLE Trial Investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,10,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfy032"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2014.10.003"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-021-00393-8"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016060666"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2017.10.026"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14601"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1515920"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14599"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/dcS15-3006"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-016-0381-x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.12707"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.2000.00749.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00547.2014"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-1141"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-021-01295-6"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(1950)3:1<32::AID-CNCR2820030106>3.0.CO;2-3"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2012.244"},{"issue":"1","key":"e_1_2_9_22_1","first-page":"S125","article-title":"Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes\u20142022","volume":"45","author":"Committee ADAPP","year":"2021","journal-title":"Diabetes Care."},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.14769"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14251"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020050723"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.34067\/KID.0001172021"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.10.042"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016030278"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2015.10.025"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/edm2.16"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.13772"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.02.011"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114026"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.09.013"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep45522"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfs290"},{"issue":"1","key":"e_1_2_9_37_1","first-page":"S175","article-title":"Chronic kidney disease and risk management: standards of medical care in diabetes\u20102022","volume":"45","author":"Draznin B","year":"2022","journal-title":"Diabetes Care."}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.14876","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.14876","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.14876","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T23:19:07Z","timestamp":1761866347000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.14876"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,23]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1111\/dom.14876"],"URL":"https:\/\/doi.org\/10.1111\/dom.14876","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/DOM.14876\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14876\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14876\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14876\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14876\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14876\/v1\/review4","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14876\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14876\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14876\/v2\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14876\/v2\/review1","asserted-by":"object"}]},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,23]]},"assertion":[{"value":"2022-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}