{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:40:14Z","timestamp":1790628014319,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T00:00:00Z","timestamp":1551657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG056479"],"award-info":[{"award-number":["R01 AG056479"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 DK007634"],"award-info":[{"award-number":["T32 DK007634"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR002489"],"award-info":[{"award-number":["UL1TR002489"]}],"id":[{"id":"10.13039\/100000002","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":[[2019,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To examine whether sodium\u2010glucose co\u2010transporter\u20102 (SGLT2) inhibitors are associated with a higher risk of lower\u2010extremity amputation than dipeptidyl\u2010peptidase\u20104 (DPP\u20104) inhibitors and sulphonylureas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study, using the MarketScan Commercial Claims and Encounters Database (2013\u20102015), to compare the incidence of lower\u2010extremity amputation (LEA) between initiators of SGLT2 inhibitors and initiators of two second\u2010line drugs, DPP\u20104 inhibitors and sulphonylureas (SUs). We estimated crude incidence rates (IRs) and adjusted hazard ratios (aHR), with 95% confidence intervals (CIs), before and after propensity\u2010score weighting. We additionally conducted sensitivity analyses using a comparator group of all non\u2010metformin, non\u2010SGLT2 inhibitor glucose\u2010lowering drugs, as previous studies used this approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In a cohort of 328 150 individuals aged 18 to 64 years, the IR of LEA ranged from 1.5 to 2.4 per 1000 person\u2010years. In as\u2010treated analysis, the estimated hazard of LEA was increased among SGLT2 inhibitor initiators compared to DPP\u20104 inhibitor initiators (aHR 1.69, 95% CI 1.20\u20102.38), but not compared to SU initiators (aHR 1.02, 95% CI 0.67\u20101.55) or non\u2010metformin, non\u2010SGLT2 inhibitor initiators (aHR 1.02, 95% CI 0.54\u20101.93). Results were consistent in intention\u2010to\u2010treat analysis and across a number of sensitivity analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Among commercially insured patients in the United States, our results suggest that initiation of SGLT2 inhibitors may increase the risk of LEA compared to initiation of DPP\u20104 inhibitors. Contrasting results when comparing SGLT2 inhibitor initiators to DPP\u20104 inhibitor and SU initiators highlight the importance of choosing appropriate comparator drugs when addressing comparative effectiveness and safety questions that can inform clinical decision\u2010making.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13647","type":"journal-article","created":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T23:18:36Z","timestamp":1548803916000},"page":"1223-1236","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Sodium\u2010glucose co\u2010transporter\u20102 inhibitor use and risk of lower\u2010extremity amputation: Evolving questions, evolving answers"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0817-983X","authenticated-orcid":false,"given":"Jeff Y.","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health University of North Carolina  Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0980-8896","authenticated-orcid":false,"given":"Tiansheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health University of North Carolina  Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Pate","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health University of North Carolina  Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1016-9910","authenticated-orcid":false,"given":"Emily W.","family":"Gower","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health University of North Carolina  Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6205-4536","authenticated-orcid":false,"given":"Matthew J.","family":"Crowley","sequence":"additional","affiliation":[{"name":"Department of Medicine Duke University School of Medicine  Durham North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9723-3876","authenticated-orcid":false,"given":"John B.","family":"Buse","sequence":"additional","affiliation":[{"name":"Department of Medicine University of North Carolina School of Medicine  Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9204-7177","authenticated-orcid":false,"given":"Til","family":"St\u00fcrmer","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Gillings School of Global Public Health University of North Carolina  Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.243"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12214"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2008.12.031"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.029190"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812389"},{"key":"e_1_2_7_9_1","first-page":"1","article-title":"Diabetes at a glance 2016","author":"Centers for Disease Control and Prevention","year":"2016","journal-title":"OECD Indic"},{"key":"e_1_2_7_10_1","unstructured":"US Food and Drug Administration. 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