Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium–Glucose Cotransporter 2 Inhibition

• DOI: 10.2337/dc15-0843
• Publication Date: 2015-06-16T01:50:49Z
• Authors: Anne L. Peters; Elizabeth O. Buschur; John B. Buse; Pejman Cohan; Jamie C. Diner; Irl B. Hirsch
• Keywords: Adult; Male; Clinical Care/Education/Nutrition/Psychosocial Research; Middle Aged; Diabetic Ketoacidosis; 3. Good health; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucosides; Humans; Hypoglycemic Agents; Female; Benzhydryl Compounds; Sodium-Glucose Transporter 2 Inhibitors; Aged

OBJECTIVE Sodium–glucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication.

RESEARCH DESIGN AND METHODS Cases identified incidentally are described.

RESULTS We identified 13 episodes of SGLT-2 inhibitor–associated euDKA or ketosis in nine individuals, seven with type 1 diabetes and two with type 2 diabetes, from various practices across the U.S. The absence of significant hyperglycemia in these patients delayed recognition of the emergent nature of the problem by patients and providers.

CONCLUSIONS SGLT-2 inhibitors seem to be associated with euglycemic DKA and ketosis, perhaps as a consequence of their noninsulin-dependent glucose clearance, hyperglucagonemia, and volume depletion. Patients with type 1 or type 2 diabetes who experience nausea, vomiting, or malaise or develop a metabolic acidosis in the setting of SGLT-2 inhibitor therapy should be promptly evaluated for the presence of urine and/or serum ketones. SGLT-2 inhibitors should only be used with great caution, extensive counseling, and close monitoring in the setting of type 1 diabetes.