{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:32:11Z","timestamp":1791977531348,"version":"4.4.0"},"reference-count":10,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T00:00:00Z","timestamp":1520812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:p>Inhibitors of the sodium\u2010glucose co\u2010transporter\u20102 (SGLT\u20102) are a novel class of glucose\u2010lowering agents that show promising results. However, the use of canagliflozin has been associated with an increased risk of lower\u2010limb amputation. Whether this risk concerns other SGLT\u20102 inhibitors is unclear, and our objective was to address this issue. We performed a disproportionality analysis using the WHO global database of individual case safety reports (VigiBase). Among the 8\u2009293\u2009886 reports available between January 2013 and December 2017, we identified 79 reports of lower\u2010limb amputation that were associated with SGLT\u20102 inhibitors. Among all blood glucose lowering drugs, the proportional reporting ratio (PRR) was increased only for SGLT\u20102 inhibitors (5.55 [4.23, 7.29]). While we observed an expected signal for canagliflozin (7.09 [5.25, 9.57]), the PRR was also high for empagliflozin (4.96 [2.89, 8.50]) and, for toe amputations only, for dapagliflozin (2.62 [1.33, 5.14]). In conclusion, our results reveal a positive disproportionality signal for canagliflozin, and also for empagliflozin, and, for toe amputations only, for dapagliflozin. However, our analysis relies on a limited number of cases and is exposed to the biases inherent to pharmacovigilance studies. Further prospective data are therefore needed to better characterize the risk of amputations with different SGLT\u20102 inhibitors.<\/jats:p>","DOI":"10.1111\/dom.13255","type":"journal-article","created":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T04:22:35Z","timestamp":1518409355000},"page":"1531-1534","source":"Crossref","is-referenced-by-count":93,"title":["SGLT\u20102 inhibitors and the risk of lower\u2010limb amputation: Is this a class effect?"],"prefix":"10.1111","volume":"20","author":[{"given":"Charles","family":"Khouri","sequence":"first","affiliation":[{"name":"Univiversity Grenoble Alpes and Grenoble Alpes University Hospital  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Luc","family":"Cracowski","sequence":"additional","affiliation":[{"name":"Univiversity Grenoble Alpes and Grenoble Alpes University Hospital  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4475-1626","authenticated-orcid":false,"given":"Matthieu","family":"Roustit","sequence":"additional","affiliation":[{"name":"Univiversity Grenoble Alpes and Grenoble Alpes University Hospital  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504720"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611925"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-1551"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30257-7"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13115"},{"key":"e_1_2_6_7_1","first-page":"CIRCULATIONAHA.","article-title":"Cardiovascular outcomes and risks after initiation of a sodium glucose co\u2010transporter 2 inhibitor: results from the EASEL population\u2010based cohort study","author":"Udell JA","year":"2017","journal-title":"Circulation"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.677"},{"key":"e_1_2_6_9_1","unstructured":"European Medicines Agency EudraVigilance Expert Working Group.Guideline on the Use of Statistical Signal Detection Methods in the EudraVigilance Data Analysis System (EMEA\/106464\/2006 rev.1).http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Regulatory_and_procedural_guideline\/2009\/11\/WC500011434.pdf. 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