{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:12:12Z","timestamp":1790957532005,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To define the proportional and absolute benefits of the sodium\u2010glucose co\u2010transporter\u20102 inhibitor canagliflozin in patients with type 2 diabetes (T2D) with and without peripheral arterial disease (PAD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We pooled individual participant data from the CANVAS Program (n\u00a0=\u00a010\u2009142) and CREDENCE trial (n\u00a0=\u00a04401). In this post hoc analysis, the main outcomes of interest were major adverse cardiovascular events (MACE: non\u2010fatal myocardial infarction, non\u2010fatal stroke or cardiovascular death), kidney outcomes, and extended major adverse limb events (MALE). Cox proportional hazards models were used to assess canagliflozin treatment effects in those with and without PAD. Absolute risk reductions per 1000 patients treated for 2.5\u2009years were estimated using Poisson regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 14\u2009543 participants, 3159 (21.7%) had PAD at baseline. In patients with PAD, canagliflozin reduced MACE (hazard ratio, 0.76; 95% confidence interval, 0.62\u20100.92), with similar relative benefits for other cardiovascular and kidney outcomes in participants with or without PAD at baseline (all\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      \u00a0&gt;\u2009.268). There was no increase in the relative risk of extended MALE with canagliflozin, irrespective of baseline PAD history (\n                      <jats:italic>P<\/jats:italic>\n                      <jats:sub>interaction<\/jats:sub>\n                      \u00a0&gt;\u2009.864). The absolute benefits of canagliflozin were greater in those with PAD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with T2D and PAD derived similar relative cardiorenal benefits from canagliflozin treatment but higher absolute benefits compared with those without PAD, with no increase in extended MALE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14671","type":"journal-article","created":{"date-parts":[[2022,2,15]],"date-time":"2022-02-15T04:33:37Z","timestamp":1644899617000},"page":"1072-1083","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Cardiovascular and renal outcomes with canagliflozin in patients with peripheral arterial disease: Data from the\n                    <scp>CANVAS<\/scp>\n                    Program and\n                    <scp>CREDENCE<\/scp>\n                    trial"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5093-9900","authenticated-orcid":false,"given":"Jennifer Y.","family":"Barraclough","sequence":"first","affiliation":[{"name":"The George Institute for Global Health University of New South Wales  Sydney New South Wales Australia"},{"name":"Department of Cardiology Royal Prince Alfred Hospital  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yu","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health University of New South Wales  Sydney New South Wales Australia"},{"name":"Department of Cardiology Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma A.","family":"Figtree","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health University of New South Wales  Sydney New South Wales Australia"},{"name":"Kolling Institute Royal North Shore Hospital and University of Sydney  Sydney New South Wales Australia"},{"name":"Sydney Medical School University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlado","family":"Perkovic","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3126-3730","authenticated-orcid":false,"given":"Hiddo J. L.","family":"Heerspink","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health University of New South Wales  Sydney New South Wales Australia"},{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9276-8380","authenticated-orcid":false,"given":"Brendon L.","family":"Neuen","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4596-2791","authenticated-orcid":false,"given":"Christopher P.","family":"Cannon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth W.","family":"Mahaffey","sequence":"additional","affiliation":[{"name":"Stanford Center for Clinical Research, Department of Medicine Stanford University School of Medicine  Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9217-4937","authenticated-orcid":false,"given":"Aletta E.","family":"Schutte","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0490-7465","authenticated-orcid":false,"given":"Bruce","family":"Neal","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health University of New South Wales  Sydney New South Wales Australia"},{"name":"The Charles Perkins Centre University of Sydney  Sydney New South Wales Australia"},{"name":"Department of Epidemiology and Biostatistics Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9370-9913","authenticated-orcid":false,"given":"Clare","family":"Arnott","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health University of New South Wales  Sydney New South Wales Australia"},{"name":"Department of Cardiology Royal Prince Alfred Hospital  Sydney New South Wales Australia"},{"name":"Sydney Medical School University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303849"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61249-0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(19)30255-4"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.09.065"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v6.i7.961"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199202063260605"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2008.10.023"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2014.05.008"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2006.04.002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.11.1317"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024816"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911303"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022190"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.014908"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.044775"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2019.05.028"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32409-1"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12829"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2013.05.007"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1159\/000484633"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-019-4839-8"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2020.06.018"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2019010064"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14091"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu080"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.11.3026"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(18)30290-0"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.2459\/01.JCM.0000237909.26377.9f"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.032235"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1067\/mhj.2003.6"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.03.013"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.03.524"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-5299.2007.07344.x"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfq070"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.017174"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2012.02.340"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2021.04.029"},{"key":"e_1_2_9_43_1","unstructured":"FDAFDA removes boxed warning about risk of leg and foot amputations for the diabetes medicine canagliflozin (Invokana Invokamet Invokamet XR); 2017."}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.14671","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.14671","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.14671","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T03:42:10Z","timestamp":1761882130000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.14671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,7]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["10.1111\/dom.14671"],"URL":"https:\/\/doi.org\/10.1111\/dom.14671","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,7]]},"assertion":[{"value":"2021-12-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}