{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T09:00:47Z","timestamp":1790586047063,"version":"4.1.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Endocrinol Invest"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sodium-glucose co-transporter-2 (SGLT2) inhibitors are widely prescribed to diabetic patients for their cardiorenal benefits. However, concerns over adverse events\u2014specifically amputation risk and gangrene\u2014have risen in recent years. This study aimed to describe the frequency and severity of these events in relation to SGLT2 inhibitor use, using the U.S. FDA Adverse Event Reporting System (FAERS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>OpenVigil 2.1 was used to extract safety reports submitted to FAERS from 2003 Q4 to 2024 Q4. Amputation and gangrene events linked to SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin) were identified and compared to other drugs. Reporting odds ratios (RORs) were calculated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 3,540 adverse event reports were identified: 2,128 for canagliflozin, 361 for dapagliflozin, 1,049 for empagliflozin, and 2 for ertugliflozin. Canagliflozin was strongly associated with toe amputation (ROR\u2009=\u2009635.6; 95%CI: 566.7\u2013712.1), foot amputation (ROR\u2009=\u2009201.8; 95%CI: 174.3\u2013233.7), and Fournier\u2019s gangrene (ROR\u2009=\u2009117.5; 95%CI: 100.0\u2013138.0). Empagliflozin was linked with Fournier\u2019s gangrene (ROR\u2009=\u2009565.2; 95%CI: 525.3\u2013608.2) and toe amputation (ROR\u2009=\u200921.2; 95%CI: 17.6\u201325.6). Dapagliflozin showed weaker signals; ertugliflozin had minimal data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Toe amputation and Fournier\u2019s gangrene were most reported with canagliflozin and empagliflozin, reinforcing prior safety concerns and the need for monitoring.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s40618-026-02809-3","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T10:16:09Z","timestamp":1767867369000},"page":"1381-1390","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Amputation and gangrene associated with SGLT2 inhibitors: pharmacovigilance analysis of the FDA adverse event reporting system (FAERS) database"],"prefix":"10.1007","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5154-6183","authenticated-orcid":false,"given":"Alyaa M.","family":"Ajabnoor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"issue":"12","key":"2809_CR1","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1016\/S2213-8587(19)30154-8","volume":"7","author":"SI Taylor","year":"2019","unstructured":"Taylor SI, Blau JE, Rother KI, Beitelshees AL (2019) SGLT2 inhibitors as adjunctive therapy for type 1 diabetes: balancing benefits and risks. Lancet Diabetes Endocrinol 7(12):949\u2013958. https:\/\/doi.org\/10.1016\/S2213-8587(19)30154-8","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"4","key":"2809_CR2","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1056\/NEJMoa1812389","volume":"380","author":"SD Wiviott","year":"2019","unstructured":"Wiviott SD, Raz I, Bonaca MP et al (2019) Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 380(4):347\u2013357. https:\/\/doi.org\/10.1056\/NEJMoa1812389","journal-title":"N Engl J Med"},{"issue":"7","key":"2809_CR3","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1056\/NEJMoa1611925","volume":"377","author":"B Neal","year":"2017","unstructured":"Neal B, Perkovic V, Mahaffey KW et al (2017) Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 377(7):644\u2013657. https:\/\/doi.org\/10.1056\/NEJMoa1611925","journal-title":"N Engl J Med"},{"issue":"22","key":"2809_CR4","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","volume":"373","author":"B Zinman","year":"2015","unstructured":"Zinman B, Wanner C, Lachin JM et al (2015) Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373(22):2117\u20132128. https:\/\/doi.org\/10.1056\/NEJMoa1504720","journal-title":"N Engl J Med"},{"issue":"12","key":"2809_CR5","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1007\/s40618-023-02162-9","volume":"46","author":"G Bendotti","year":"2023","unstructured":"Bendotti G, Montefusco L, Pastore I, Lazzaroni E, Lunati ME, Fiorina P (2023) The anti-inflammatory and immunological properties of SGLT-2 inhibitors. J Endocrinol Invest 46(12):2445\u20132452. https:\/\/doi.org\/10.1007\/s40618-023-02162-9","journal-title":"J Endocrinol Invest"},{"key":"2809_CR6","unstructured":"USFDA (2018) FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes. Accessed March 4, 2025. https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/fda-warns-about-rare-occurrences-serious-infection-genital-area-sglt2-inhibitors-diabetes"},{"key":"2809_CR7","unstructured":"USFDA (2016) FDA strengthens kidney warnings for diabetes medicines canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR). Accessed March 4, 2025.\u00a0https:\/\/www.fda.gov\/media\/98683\/download"},{"key":"2809_CR8","unstructured":"USFDA (2015) FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. 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