Euglycemic Ketoacidosis Caused by Sodium–Glucose Cotransporter 2 Inhibitors: A Case Report
Authors: Shane A. Bobart, Benjamin Gleason, Nydia Martinez, Keith Norris, Sandra F. Williams
Journal: Annals of Internal Medicine (2016)

Letters4 October 2016Euglycemic Ketoacidosis Caused by Sodium–Glucose Cotransporter 2 Inhibitors: A Case ReportShane A. Bobart, MD, Benjamin Gleason, MD, Nydia Martinez, MD, Keith Norris, MD, PhD, and Sandra F. Williams, MDShane A. Bobart, MDFrom Cleveland Clinic Florida, Weston, Florida, and University of California, Los Angeles, Los Angeles, California.Search for more papers by this author, Benjamin Gleason, MDFrom Cleveland Clinic Florida, Weston, Florida, and University of California, Los Angeles, Los Angeles, California.Search for more papers by this author, Nydia Martinez, MDFrom Cleveland Clinic Florida, Weston, Florida, and University of California, Los Angeles, Los Angeles, California.Search for more papers by this author, Keith Norris, MD, PhDFrom Cleveland Clinic Florida, Weston, Florida, and University of California, Los Angeles, Los Angeles, California.Search for more papers by this author, and Sandra F. Williams, MDFrom Cleveland Clinic Florida, Weston, Florida, and University of California, Los Angeles, Los Angeles, California.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L15-0535 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: Sodium–glucose cotransporter 2 (SGLT-2) inhibitors decrease blood glucose levels in patients with type 2 diabetes mellitus (T2DM) by inhibiting glucose reuptake in the proximal renal tubule, which induces glycosuria and renal wasting of glucose. The U.S. Food and Drug Administration recently issued a drug safety communication reporting 73 cases of ketoacidosis associated with these agents (1).Objective: To propose a mechanism for ketoacidosis associated with SGLT-2 inhibitors.Case Report: A woman in her mid-40s presented with dyspnea, nausea, and vomiting 2 days after cosmetic surgery. She had T2DM and was receiving metformin, 1000 mg twice daily; liraglutide (a glucagon-like ...References1. U.S. Food and Drug Administration. FDA drug safety communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. Accessed at www.fda.gov/Drugs/DrugSafety/ucm475463.htm on 17 December 2015. Google Scholar2. Erondu N, Desai M, Ways K, Meininger G. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care. 2015;38:1680-6. [PMID: 26203064] doi:10.2337/dc15-1251 CrossrefMedlineGoogle Scholar3. Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015;38:1687-93. [PMID: 26078479] doi:10.2337/dc15-0843 CrossrefMedlineGoogle Scholar4. Bonner C, Kerr-Conte J, Gmyr V, Queniat G, Moerman E, Thévenet J, et al. Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat Med. 2015;21:512-7. [PMID: 25894829] doi:10.1038/nm.3828 CrossrefMedlineGoogle Scholar5. Poudel R. Renal glucose handling in diabetes and SGLT-2 inhibition. Indian J Endocrinol Metab. 2013;17:588-93. CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Cleveland Clinic Florida, Weston, Florida, and University of California, Los Angeles, Los Angeles, California.Presented in part at the American College of Physicians' 2015 Florida Annual Chapter Scientific Meeting, Tampa, Florida, 11–13 September 2015.Acknowledgment: The authors thank Jonathan Schroeder, MD.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L15-0535. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAnnals On Call - SGLT2 Inhibitors: The Good, the Bad, and the Ugly Robert M. Centor and Katherine Tuttle Metrics Cited bySodium-glucose cotransporter 2 inhibitor-associated perioperative ketoacidosis: a systematic review of case reportsEuglycemic diabetic ketoacidosis in a patient with type 2 diabetes mellitus 3 days after initiating sodium‐glucose cotransporter 2 inhibitor while on an extremely low carbohydrate diet: A case reportPerioperative diabetic ketoacidosis associated with sodium-glucose co-transporter-2 inhibitors: a systematic reviewSodium-glucose co-transporter type-2 inhibitors: pharmacology and peri-operative considerationsTwenty years of adverse drug reactions: a look back – part 2Sodium‐glucose co‐transporter‐2 inhibitors and diabetic ketoacidosis: A n updated review of the literatureCanagliflozin 4 October 2016Volume 165, Issue 7Page: 530-532KeywordsAnionsBicarbonatesGlucagonGluconeogenesisGlucoseGlycogensInsulinSodiumType 2 diabetesVomiting ePublished: 4 October 2016 Issue Published: 4 October 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. 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