{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:16:00Z","timestamp":1789172160682,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Pharmacokinetic data suggest a potential dose\u2010dependent effect of sodium\u2013glucose co\u2010transporter\u20102 (SGLT\u20102) inhibitors on surrogate markers of efficacy, but the impact of SGLT\u20102 inhibitor dose on renal and cardiovascular outcomes remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this post hoc analysis, we evaluated the efficacy and safety of two canagliflozin doses (100 and 300\u2009mg) on hard clinical endpoints using participant\u2010level data from the CANVAS randomised controlled trial (4330 patients). The primary outcome was a composite of doubling of serum creatinine, renal failure, or death due to renal cause. Secondary outcomes included a composite cardiovascular endpoint; hospitalisation for heart failure; all\u2010cause mortality; and progression or regression of albuminuria. Safety outcomes included serious hyperkalaemia and acute kidney injury. Cox proportional hazards models were used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      There was no significant difference in the composite renal endpoint between the two doses: hazard ratio (HR) 0.85; 95% confidence interval (CI) 0.38\u20131.89 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.68). Both doses, however, were associated with significant reductions in the incidence of the primary renal endpoint compared with placebo: HR 0.49 (95% CI 0.25\u20130.95;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03) for 100\u2009mg and HR 0.41 (95% CI 0.20\u20130.83;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01) for 300\u2009mg. There was no difference between the two doses of the drug in any of the secondary endpoints. Importantly, no added safety concerns were identified with either dose.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this post hoc analysis of the CANVAS trial, we did not observe evidence of a dose\u2010dependent effect of canagliflozin on renal or cardiovascular outcomes. Both doses reduced the risk of kidney events versus placebo, suggesting clinical benefit at any dose.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70886","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T01:31:39Z","timestamp":1780277499000},"page":"7083-7093","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of Canagliflozin Dose on Renal and Cardiovascular Outcomes in Type 2 Diabetes and High Cardiovascular Risk"],"prefix":"10.1111","volume":"28","author":[{"given":"Elias John","family":"Elenjickal","sequence":"first","affiliation":[{"name":"Department of Medicine McGill University Health Center  Montreal Canada"},{"name":"Research Institute of the McGill University Health Center  Montreal Canada"},{"name":"Department of Nephrology Christian Medical College  Vellore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Baroz","sequence":"additional","affiliation":[{"name":"Department of Medicine McGill University Health Center  Montreal Canada"},{"name":"Research Institute of the McGill University Health Center  Montreal Canada"},{"name":"Department of Medicine Geneva University Hospitals  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Boileau","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Biostatistics, and Occupational Health McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8326-7274","authenticated-orcid":false,"given":"Michael A.","family":"Tsoukas","sequence":"additional","affiliation":[{"name":"Department of Medicine McGill University Health Center  Montreal Canada"},{"name":"Research Institute of the McGill University Health Center  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2346-8330","authenticated-orcid":false,"given":"Abhinav","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Medicine McGill University Health Center  Montreal Canada"},{"name":"Research Institute of the McGill University Health Center  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3368-247X","authenticated-orcid":false,"given":"Thomas A.","family":"Mavrakanas","sequence":"additional","affiliation":[{"name":"Department of Medicine McGill University Health Center  Montreal Canada"},{"name":"Research Institute of the McGill University Health Center  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204233"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024816"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2030186"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911303"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022190"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107038"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.0000000693"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-42989-z"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00956-1"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12134248"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.12322"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-022-01296-y"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-023-02126-8"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14452"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2024.7357"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-1347"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-2673"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12924"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2013.05.007"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12829"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxt050"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.55.2208"},{"key":"e_1_2_11_28_1","unstructured":"T. M.Therneau \u201cA Package for Survival Analysis in R. R Package Version 3.2\u20137 \u201d2020 https:\/\/CRAN.R\u2010project.org\/package=survival."},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.20945\/2359-3997000000440"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ipha.2025.02.001"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1256548"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2024-088687"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2020.04.009"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.34067\/KID.0007862021"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44324-025-00068-z"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.88"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-025-01571-8"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.116.232025"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9072275"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/adtp.202300143"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13630"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0126-x"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12453"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.edurev.2023.100590"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.4103\/IJPSYM.IJPSYM_499_18"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.70886","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.70886","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.70886","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:46:05Z","timestamp":1789170365000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/10.1111\/dom.70886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,31]]},"references-count":44,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/dom.70886"],"URL":"https:\/\/doi.org\/10.1111\/dom.70886","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/DOM.70886\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70886\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70886\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70886\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70886\/v1\/review5","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70886\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70886\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70886\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70886\/v1\/review4","asserted-by":"object"}]},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,31]]},"assertion":[{"value":"2026-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}