{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:10:57Z","timestamp":1789726257664,"version":"4.0.1"},"reference-count":24,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"vor","delay-in-days":200,"URL":"http:\/\/www.diabetesjournals.org\/site\/license"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research & Development, LLC","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,4,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>To assess the incidence of serious adverse events (AEs) of diabetic ketoacidosis (DKA) with canagliflozin, a sodium\u2013glucose cotransporter 2 inhibitor, as an add-on to insulin in adults with type 1 diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>In this 18-week, randomized, double-blind, phase 2 study, patients (N = 351; HbA1c 7.0\u20139.0% [53\u201375 mmol\/mol]) on multiple daily insulin injections or continuous subcutaneous insulin infusion received canagliflozin 100 or 300 mg or placebo once daily. The incidence of ketone-related AEs, defined as any event from a prespecified list of preferred terms (i.e., acidosis, blood ketone body increased, blood ketone body present, DKA, diabetic ketoacidotic hyperglycemic coma, ketoacidosis, ketonemia, ketonuria, ketosis, metabolic acidosis, urine ketone body present), including serious AEs of DKA, was assessed based on AE reports.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>At week 18, the incidence of any ketone-related AE with canagliflozin 100 and 300 mg was 5.1% (n = 6 of 117) and 9.4% (n = 11 of 117), respectively; no patients in the placebo group experienced a ketone-related AE. The incidence of serious AEs of DKA was 4.3% (n = 5 of 117) with canagliflozin 100 mg and 6.0% (n = 7 of 117) with canagliflozin 300 mg; all serious events occurred in the presence of circumstances that are known to potentially precipitate DKA (e.g., infection, insulin pump failure). Among the 12 patients with a serious AE of DKA, blood glucose levels ranged from 9.4 to &amp;gt;44.4 mmol\/L (170 to &amp;gt;800 mg\/dL). Baseline characteristics were generally similar in patients with and without a ketone-related AE.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Canagliflozin was associated with an increased incidence of serious AEs of DKA in patients with type 1 diabetes inadequately controlled with insulin. Mitigation strategies are needed for use in future clinical trials to reduce the risk of DKA with canagliflozin treatment in patients with type 1 diabetes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc15-1995","type":"journal-article","created":{"date-parts":[[2016,3,18]],"date-time":"2016-03-18T02:50:10Z","timestamp":1458269410000},"page":"532-538","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":86,"title":["Diabetic Ketoacidosis With Canagliflozin, a Sodium\u2013Glucose Cotransporter 2 Inhibitor, in Patients With Type 1 Diabetes"],"prefix":"10.2337","volume":"39","author":[{"given":"Anne L.","family":"Peters","sequence":"first","affiliation":[{"name":"Keck School of Medicine of the University of Southern California, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R.","family":"Henry","sequence":"additional","affiliation":[{"name":"Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA"},{"name":"University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payal","family":"Thakkar","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC, Raritan, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Tong","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC, Raritan, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Alba","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, LLC, Raritan, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2016,3,15]]},"reference":[{"key":"2022031220202213800_B1","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.2337\/dc09-9032","article-title":"Hyperglycemic crises in adult patients with diabetes","volume":"32","author":"Kitabchi","year":"2009","journal-title":"Diabetes Care"},{"key":"2022031220202213800_B2","first-page":"1705","article-title":"Diabetic ketoacidosis","volume":"71","author":"Trachtenbarg","year":"2005","journal-title":"Am Fam Physician"},{"key":"2022031220202213800_B3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s40138-012-0001-3","article-title":"Diabetic ketoacidosis: a review and update","volume":"1","author":"Perilli","year":"2013","journal-title":"Curr Emerg Hosp Med Rep"},{"key":"2022031220202213800_B4","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1002\/dmrr.877","article-title":"Diabetes classification: grey zones, sound and smoke: Action LADA 1","volume":"24","author":"Leslie","year":"2008","journal-title":"Diabetes Metab Res Rev"},{"key":"2022031220202213800_B5","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1111\/dme.12700","article-title":"Latent autoimmune diabetes of the adult: current knowledge and uncertainty","volume":"32","author":"Laugesen","year":"2015","journal-title":"Diabet Med"},{"key":"2022031220202213800_B6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.2337\/diaspect.15.1.28","article-title":"Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome","volume":"15","author":"Umpierrez","year":"2002","journal-title":"Diabetes Spectr"},{"key":"2022031220202213800_B7","unstructured":"Food and Drug Administration. FDA drug safety communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood [article online], 2015. Available from http:\/\/www.fda.gov\/Drugs\/DrugSafety\/ucm446845.htm. Accessed 19 May 2015"},{"key":"2022031220202213800_B8","unstructured":"European Medicines Agency. Review of diabetes medicines called SGLT2 inhibitors started. Risk of diabetic ketoacidosis to be examined [article online], 2015. Available from http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/medicines\/human\/referrals\/SGLT2_inhibitors\/human_referral_prac_000052.jsp&mid=WC0b01ac05805c516f. 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