{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:06:24Z","timestamp":1791223584850,"version":"4.1.0"},"reference-count":30,"publisher":"American Diabetes Association","issue":"10","license":[{"start":{"date-parts":[[2018,9,20]],"date-time":"2018-09-20T00:00:00Z","timestamp":1537401600000},"content-version":"vor","delay-in-days":49,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,10,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Diabetes-related foot ulcers (DFUs) and their sequelae result in large patient and societal burdens. Long-term data determining the efficacy of individual glucose-lowering agents on DFUs are lacking. Using existing data from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, we conducted post hoc analyses assessing the impact of liraglutide versus placebo in people with type 2 diabetes and at high risk of cardiovascular (CV) events on the incidence of DFUs and their sequelae.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>The LEADER trial (NCT01179048) was a randomized, double-blind, multicenter, CV outcomes trial assessing liraglutide (1.8 mg\/day) versus placebo, in addition to standard of care, for up to 5 years. Information on DFUs was collected systematically during the trial, and DFU complications were assessed post hoc through reviewing case narratives.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>During a median of 3.8 years\u2019 follow-up, similar proportions of patients reported at least one episode of DFU in the liraglutide and placebo groups (3.8% [176\/4,668] versus 4.1% [191\/4,672], respectively; hazard ratio [HR] 0.92 [95% CI 0.75, 1.13; P = 0.41]). Analysis of DFU-related complications demonstrated a significant reduction in amputations with liraglutide versus placebo (HR 0.65 [95% CI 0.45, 0.95; P = 0.03]). However, no differences were found for foot infections, involvement of underlying structures, or peripheral revascularization in the main analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Treatment with liraglutide in patients with type 2 diabetes and at high risk of CV events in the LEADER trial did not increase the risk of DFU events and was associated with a significantly lower risk of DFU-related amputations compared with placebo. This association, possibly due to chance, needs further investigation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc18-1094","type":"journal-article","created":{"date-parts":[[2018,8,2]],"date-time":"2018-08-02T20:35:18Z","timestamp":1533242118000},"page":"2229-2235","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":127,"title":["The Impact of Liraglutide on Diabetes-Related Foot Ulceration and Associated Complications in Patients With Type 2 Diabetes at High Risk for Cardiovascular Events: Results From the LEADER Trial"],"prefix":"10.2337","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct01179048","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3619-9579","authenticated-orcid":false,"given":"Ketan","family":"Dhatariya","sequence":"first","affiliation":[{"name":"Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, U.K."},{"name":"Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Bain","sequence":"additional","affiliation":[{"name":"Institute of Life Science, Swansea University Medical School, Swansea, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"Buse","sequence":"additional","affiliation":[{"name":"University of North Carolina School of Medicine, Chapel Hill, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Simpson","sequence":"additional","affiliation":[{"name":"Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise","family":"Tarnow","sequence":"additional","affiliation":[{"name":"Nordsj\u00e6llands Hospital, Hiller\u00f8d, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margit Staum","family":"Kaltoft","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Stellfeld","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Torn\u00f8e","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Pratley","sequence":"additional","affiliation":[{"name":"Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the LEADER Publication Committee on behalf of the LEADER Trial Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2018,8,2]]},"reference":[{"key":"2022031301233970600_B1","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1056\/NEJMra1615439","article-title":"Diabetic foot ulcers and their recurrence","volume":"376","author":"Armstrong","year":"2017","journal-title":"N Engl J Med"},{"key":"2022031301233970600_B2","doi-asserted-by":"crossref","first-page":"491","DOI":"10.2337\/diacare.26.2.491","article-title":"Amputation and mortality in new-onset diabetic foot ulcers stratified by etiology","volume":"26","author":"Moulik","year":"2003","journal-title":"Diabetes Care"},{"key":"2022031301233970600_B3","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.2337\/dc10-1213","article-title":"Impact of chronic kidney disease on survival after amputation in individuals with diabetes","volume":"33","author":"Lavery","year":"2010","journal-title":"Diabetes Care"},{"key":"2022031301233970600_B4","unstructured":"Office for National Statistics. 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