{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:26:13Z","timestamp":1778768773490,"version":"3.51.4"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,10,15]],"date-time":"2019-10-15T00:00:00Z","timestamp":1571097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp; Metabol"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>In the EASEL study of patients with type 2 diabetes and high cardiovascular risk, initiation of sodium glucose co\u2010transporter 2 inhibitors (SGLT2i) was associated with lower risk of cardiovascular events and mortality and higher risk of below\u2010knee lower extremity (BKLE) amputation versus non\u2010SGLT2i therapies. This analysis further examined risk of cardiovascular events, cardiovascular and noncardiovascular death and BKLE amputation with the SGLT2i canagliflozin versus non\u2010SGLT2i.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>New user cohorts were constructed from Department of Defense Military Health System patients initiating canagliflozin or non\u2010SGLT2i (4\/1\/2013\u201012\/31\/2016). Propensity score matching (1:1) controlled for imbalances in baseline covariates. Incidence rates, hazard ratios and 95% confidence intervals for time to first composite outcome of all\u2010cause mortality (ACM) and hospitalization for heart failure (HHF), composite major adverse cardiovascular events (MACE) and individual components were evaluated using conditional Cox models. The National Death Index was used to differentiate cardiovascular from noncardiovascular death. The exploratory safety end\u2010point was BKLE amputation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After propensity matching, 15\u00a0394 patients with well\u2010balanced baseline covariates were followed for a median of 2.03\u00a0years (intent\u2010to\u2010treat). Canagliflozin showed significant benefit for ACM and HHF (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.0001), MACE (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.0001), cardiovascular death (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.0001) and noncardiovascular death (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.0018). No significant difference in risk of BKLE amputation was observed (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.20), though few events were observed. Results were generally consistent in on\u2010treatment analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this high cardiovascular risk cohort studied in routine clinical practice, canagliflozin was associated with lower risk of cardiovascular events, cardiovascular death and all\u2010cause mortality with no significant increase in BKLE amputation risk versus non\u2010SGLT2i.<\/jats:p><\/jats:sec>","DOI":"10.1002\/edm2.96","type":"journal-article","created":{"date-parts":[[2019,10,15]],"date-time":"2019-10-15T08:41:47Z","timestamp":1571128907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Cardiovascular outcomes and mortality after initiation of canagliflozin: Analyses from the EASEL Study"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7402-9584","authenticated-orcid":false,"given":"Jacob A.","family":"Udell","sequence":"first","affiliation":[{"name":"Department of Medicine Cardiovascular Division Peter Munk Cardiac Centre Toronto General Hospital and Women\u2019s College Hospital University of Toronto Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5824-2040","authenticated-orcid":false,"given":"Zhong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC Titusville NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9727-2138","authenticated-orcid":false,"given":"Patrick","family":"Ryan","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC Titusville NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toni","family":"Rush","sequence":"additional","affiliation":[{"name":"Health ResearchTx, LLC Trevose PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas M.","family":"Sicignano","sequence":"additional","affiliation":[{"name":"Health ResearchTx, LLC Trevose PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Galitz","sequence":"additional","affiliation":[{"name":"Naval Medical Center Portsmouth VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norman","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC Raritan NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13459"},{"key":"e_1_2_10_3_1","volume-title":"Heart and Stroke Statistics","author":"American Heart Association","year":"2018"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/acem.12078"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1067\/mhj.2002.123839"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.024764"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0218919"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506115"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx511"},{"key":"e_1_2_10_10_1","first-page":"339","volume-title":"Patterns of Health Care in Ontario: The ICES Practice Atlas","author":"Williams JI","year":"1996"},{"key":"e_1_2_10_11_1","unstructured":"Health ResearchTx. 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