{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:21:55Z","timestamp":1792077715835,"version":"4.4.0"},"reference-count":40,"publisher":"American Diabetes Association","issue":"10","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["1R03DK140420"],"award-info":[{"award-number":["1R03DK140420"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["1K23DK122126"],"award-info":[{"award-number":["1K23DK122126"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>To compare the risk of lower-extremity amputations (LEAs) between new users of glucagon-like peptide 1 receptor agonists (GLP-1RAs) versus sodium\u2013glucose cotransporter 2 inhibitors (SGLT2is).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>This retrospective cohort study used TriNetX, a federated electronic health records network, including adults with type 2 diabetes who initiated GLP-1RAs or SGLT2is between May 2013 and March 2025. Propensity score matching (1:1) was used to balance demographics, comorbidities, medications, and laboratory values. Major (above-ankle) amputation\u2013free survival was evaluated using Kaplan-Meier curves, while risks of major and minor LEAs, diabetic foot ulcers (DFUs), and mortality were estimated using hazard ratios (HRs) with 95% CIs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The matched cohorts included 180,740 GLP-1RA and 180,740 SGLT2i recipients. At 3 years, the GLP-1RA cohort was associated with greater major amputation\u2013free survival (99.69% vs. 99.64%, P = 0.001) compared with the SGLT2i cohort. Additionally, GLP-1RA treatment was associated with a lower risk of major LEAs (HR 0.77 [95% CI 0.66, 0.90]), minor LEAs (HR 0.73 [95% CI 0.63, 0.84]), DFUs (HR 0.92 [95% CI 0.87, 0.96]), and mortality (HR 0.66 [95% CI 0.63, 0.69]). Risk reduction for major LEAs remained significant in individuals with peripheral artery disease (HR 0.68 [95% CI 0.56, 0.82]) and DFUs (HR 0.70 [95% CI 0.58, 0.84]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>GLP-1RA treatment was associated with greater major amputation\u2013free survival compared with SGLT2i in people with type 2 diabetes, particularly in high-risk subgroups. Prospective studies are needed to confirm findings and inform selection of glucose-lowering therapies for people at risk for diabetes-related amputations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc25-0292","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T11:50:51Z","timestamp":1750852251000},"page":"1728-1736","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":24,"title":["Differential Effect of GLP-1 Receptor Agonists and SGLT2 Inhibitors on Lower-Extremity Amputation Outcomes in Type 2 Diabetes: A Nationwide Retrospective Cohort Study"],"prefix":"10.2337","volume":"48","author":[{"given":"Alexander T.","family":"Hong","sequence":"first","affiliation":[{"name":"Keck School of Medicine, University of Southern California 1 , Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan Y.","family":"Luu","sequence":"additional","affiliation":[{"name":"Keck School of Medicine, University of Southern California 1 , Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Forest","family":"Lin","sequence":"additional","affiliation":[{"name":"Keck School of Medicine, University of Southern California 1 , Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Shin","sequence":"additional","affiliation":[{"name":"Keck School of Medicine, University of Southern California 1 , Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiu-Hsieh","family":"Hsu","sequence":"additional","affiliation":[{"name":"Mel & Enid Zuckerman College of Public Health, University of Arizona 2 , Tucson, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Ding","family":"Shih","sequence":"additional","affiliation":[{"name":"Keck School of Medicine, University of Southern California 1 , Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Keck School of Medicine, University of Southern California 1 , Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6658-9482","authenticated-orcid":false,"given":"Tze-Woei","family":"Tan","sequence":"additional","affiliation":[{"name":"Keck School of Medicine, University of Southern California 1 , Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"2026061714383330400_B1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00125-022-05845-9","article-title":"Global trends in the incidence of hospital admissions for diabetes-related foot disease and amputations: a review of national rates in the 21st century","volume":"66","author":"Lazzarini","year":"2023","journal-title":"Diabetologia"},{"key":"2026061714383330400_B2","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1001\/jama.2023.10578","article-title":"Diabetic foot ulcers: a review","volume":"330","author":"Armstrong","year":"2023","journal-title":"JAMA"},{"key":"2026061714383330400_B3","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2337\/dc21-1596","article-title":"Foot ulcer and risk of lower limb amputation or death in people with diabetes: a national population-based retrospective cohort study","volume":"45","author":"Chamberlain","year":"2022","journal-title":"Diabetes Care"},{"key":"2026061714383330400_B4","doi-asserted-by":"crossref","first-page":"8866126","DOI":"10.1155\/2021\/8866126","article-title":"Amputations of lower limb in subjects with diabetes mellitus: reasons and 30-day mortality","volume":"2021","author":"Walicka","year":"2021","journal-title":"J Diabetes Res"},{"key":"2026061714383330400_B5","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1007\/s00125-004-1463-y","article-title":"The diabetic foot: from art to science. 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