title: SGLT2 Inhibitor-associated Diabetic Ketoacidosis: Clinical Review and Recommendations for Prevention and Diagnosis.
abstract: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest class of antihyperglycemic agents available on the market. Regulator warnings and concerns regarding the risk of developing diabetic ketoacidosis (DKA), however, have dampened enthusiasm for the class despite the combined glycemic, blood pressure, and occasional weight benefits of SGLT2 inhibitors. With the goal of improving patient safety, a cross-Canada expert panel and writing group were convened to review the evidence to-date on reported SGLT2 inhibitor-related DKA incidents and to offer recommendations for preventing and recognizing patients with SGLT2 inhibitor-associated DKA.
  
  
  
  Reports covering DKA events in subjects taking SGLT2 inhibitors that were published in PubMed, presented at professional conferences, or in the public domain from January 2013 to mid-August 2016 were reviewed by the group independently and collectively. Practical recommendations for diagnosis and prevention were established by the panel.
  
  
  
  DKA is rarely associated with SGLT2 inhibitor therapy. Patients with SGLT2 inhibitor-associated DKA may be euglycemic (plasma glucose level <14 mmol/L). DKA is more likely in patients with insulin-deficient diabetes, including those with type 2 diabetes, and is typically precipitated by insulin omission or dose reduction, severe acute illness, dehydration, extensive exercise, surgery, low-carbohydrate diets, or excessive alcohol intake. SGLT2 inhibitor-associated DKA may be prevented by withholding SGLT2 inhibitors when precipitants develop, avoiding insulin omission or inappropriate insulin dose reduction, and by following sick day protocols as recommended.
  
  
  
  Preventive strategies should help avoid SGLT2 inhibitor-associated DKA. All SGLT2 inhibitor-treated patients presenting with signs or symptoms of DKA should be suspected to have DKA and be investigated for DKA, especially euglycemic patients. If DKA is diagnosed, SGLT2 inhibitor treatment should be stopped, and the DKA should be treated with a traditional treatment protocol.
authors.affiliation: LMC Diabetes & Endocrinology, Thornhill, Ontario, Canada. Electronic address: ronaldgoldenberg@gmail.com.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Goldenberg
authors.affiliation: Winnipeg Regional Health Authority Health Sciences Centre, University of Manitoba, Diabetes Research Group, Winnipeg, Manitoba, Canada.
authors.forename: Lori D
authors.initials: LD
authors.lastname: Berard
authors.affiliation: Division of Endocrinology and Metabolism, St. Michael׳s Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Alice Y Y
authors.initials: AYY
authors.lastname: Cheng
authors.affiliation: Division of Endocrinology and Metabolism, Sunnybrook Health Sciences Centre, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Gilbert
authors.affiliation: Division of Cardiac Surgery, St. Michael׳s Hospital, Departments of Surgery and Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Subodh
authors.initials: S
authors.lastname: Verma
authors.affiliation: Section of Endocrinology and Metabolism, Health Sciences Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Woo
authors.affiliation: Division of Endocrinology and Metabolism, McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Yale
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D002170:Canada / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D016883:Diabetic Ketoacidosis / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D015994:Incidence; D007328:Insulin / Q000008:administration & dosage; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
keywords: SGLT2 inhibitors; diabetic ketoacidosis; euglycemia; insulin