{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:20:40Z","timestamp":1790774440213,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,10,11]],"date-time":"2017-10-11T00:00:00Z","timestamp":1507680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/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":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To examine the incidence of amputation in patients with type 2 diabetes mellitus (T2DM) treated with sodium glucose co\u2010transporter 2 (SGLT2) inhibitors overall, and canagliflozin specifically, compared with non\u2010SGLT2 inhibitor antihyperglycaemic agents (AHAs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Patients with T2DM newly exposed to SGLT2 inhibitors or non\u2010SGLT2 inhibitor AHAs were identified using the Truven MarketScan database. The incidence of below\u2010knee lower extremity (BKLE) amputation was calculated for patients treated with SGLT2 inhibitors, canagliflozin, or non\u2010SGLT2 inhibitor AHAs. Patients newly exposed to canagliflozin and non\u2010SGLT2 inhibitor AHAs were matched 1:1 on propensity scores, and a Cox proportional hazards model was used for comparative analysis. Negative controls (outcomes not believed to be associated with any AHA) were used to calibrate\n                      <jats:italic>P<\/jats:italic>\n                      values.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Between April 1, 2013 and October 31, 2016, 118\u2009018 new users of SGLT2 inhibitors, including 73\u2009024 of canagliflozin, and 226\u2009623 new users of non\u2010SGLT2 inhibitor AHAs were identified. The crude incidence rates of BKLE amputation were 1.22, 1.26 and 1.87 events per 1000 person\u2010years with SGLT2 inhibitors, canagliflozin and non\u2010SGLT2 inhibitor AHAs, respectively. For the comparative analysis, 63\u2009845 new users of canagliflozin were matched with 63\u2009845 new users of non\u2010SGLT2 inhibitor AHAs, resulting in well\u2010balanced baseline covariates. The incidence rates of BKLE amputation were 1.18 and 1.12 events per 1000 person\u2010years with canagliflozin and non\u2010SGLT2 inhibitor AHAs, respectively; the hazard ratio was 0.98 (95% confidence interval 0.68\u20131.41;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.92, calibrated\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.95).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This real\u2010world study observed no evidence of increased risk of BKLE amputation for new users of canagliflozin compared with non\u2010SGLT2 inhibitor AHAs in a broad population of patients with T2DM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13115","type":"journal-article","created":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T12:24:08Z","timestamp":1505219048000},"page":"582-589","source":"Crossref","is-referenced-by-count":105,"title":["Risk of lower extremity amputations in people with type 2 diabetes mellitus treated with sodium\u2010glucose co\u2010transporter\u20102 inhibitors in the USA: A retrospective cohort study"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5824-2040","authenticated-orcid":false,"given":"Zhong","family":"Yuan","sequence":"first","affiliation":[{"name":"Janssen Research &amp; Development LLC  Titusville New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank J.","family":"DeFalco","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development LLC  Raritan New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick B.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development LLC  Titusville New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn J.","family":"Schuemie","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development LLC  Titusville New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"Stang","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development LLC  Titusville New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse A.","family":"Berlin","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Titusville New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3489-1967","authenticated-orcid":false,"given":"Mehul","family":"Desai","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development LLC  Raritan New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norm","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development LLC  Raritan New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,10,11]]},"reference":[{"issue":"1","key":"e_1_2_6_2_1","first-page":"S1","article-title":"Standards of medical care in diabetes\u20102017","volume":"40","author":"American Diabetes Association","year":"2017","journal-title":"Diabetes Care"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.4.956"},{"key":"e_1_2_6_4_1","unstructured":"National Center for Chronic Disease Prevention. National diabetes statistics report 2017.https:\/\/www.cdc.gov\/diabetes\/pdfs\/data\/statistics\/national\u2010diabetes\u2010statistics\u2010report.pdf. Accessed September 21 2017."},{"key":"e_1_2_6_5_1","unstructured":"World Health Organization. Global report on diabetes 2016"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.12196"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.14310\/horm.2002.1245"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.12168"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30104-3"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1534734615593190"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00267.2015"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-0642"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12852"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0897190014566308"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12307"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_2_6_17_1","unstructured":"US Food and Drug Administration. FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana Invokamet Invokamet XR).2017.https:\/\/www.fda.gov\/downloads\/Drugs\/DrugSafety\/UCM558427.pdf. Accessed August 9 2017."},{"key":"e_1_2_6_18_1","unstructured":"INVOKANA\u00ae (canagliflozin) tablets for oral use [package insert]. Titusville NJ: Janssen Pharmaceuticals;2017."},{"key":"e_1_2_6_19_1","unstructured":"European Medicines Agency. PRAC concludes that diabetes medicine canagliflozin may contribute to risk of toe amputation. Risk may also apply to other medicines in the same class.2017.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Referrals_document\/SGLT2_inhibitors_Canagliflozin_20\/Recommendation_provided_by_Pharmacovigilance_Risk_Assessment_Committee\/WC500221431.pdf. Accessed July 5 2017."},{"key":"e_1_2_6_20_1","unstructured":"European Medicines Agency. SGLT2 inhibitors: information on potential risk of toe amputation to be included in prescribing information.2017.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Press_release\/2017\/02\/WC500222191.pdf. Accessed May 26 2017."},{"issue":"3","key":"e_1_2_6_21_1","first-page":"291","article-title":"Large\u2010scale Bayesian logistic regression for text categorization","volume":"49","author":"Genkin A","year":"2007","journal-title":"Dent Tech"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1996.tb02080.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.3263"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/pst.433"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/70.1.41"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.5925"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-014-0189-0"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000000504"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.13115","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.13115","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T05:40:24Z","timestamp":1761889224000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.13115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,11]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1111\/dom.13115"],"URL":"https:\/\/doi.org\/10.1111\/dom.13115","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,11]]}}}