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

Diabetes Care. 2015 Sep;38(9):1687-93. doi: 10.2337/dc15-0843. Epub 2015 Jun 15.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / adverse effects*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Ketoacidosis / chemically induced*
  • Diabetic Ketoacidosis / prevention & control
  • Female
  • Glucosides / administration & dosage
  • Glucosides / adverse effects*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Male
  • Middle Aged
  • Sodium-Glucose Transporter 2 Inhibitors*

Substances

  • Benzhydryl Compounds
  • Glucosides
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • empagliflozin