Euglycemic Diabetic Ketoacidosis in a Patient on Canagliflozin

Abstract

Introduction: Canagliflozin is a potent selective inhibitor of the renal proximal tubular sodium-glucose transporter 2 (SGLT2), which has been approved for glucose control in Type 2 Diabetes (T2D). It has also been used off-label in patients with Type 1 Diabetes (T1D) as adjunctive to insulin therapy, though the side effects have not been established. CASE PRESENTATION: A 45 year-old female with T1D on canagliflozin and insulin pump therapy presented to the emergency department with weakness, nausea, and emesis. The patient reported chills, fatigue, and polyuria the day prior to presentation. Repeated finger-stick glucose measurements that day ranged from 120 to 150. She developed progressively worsening non-bloody emesis, which prompted her to come to the emergency room. Laboratory testing was notable for blood glucose of 224, anion gap of 32, and a beta hydroxybutarate level of 5.89. ABG showed a pH of 7.199 and a PaCO2 of 20. The patient was admitted to the medical intensive care unit for management of diabetic ketoacidosis. Insulin pump therapy and canagliflozin were discontinued and treatment with insulin drip was initiated. While in the ICU, the patient was consistently euglycemic while maintaining an anion gap. After 2 days the patient's ketoacidosis had resolved, and patient was restarted on insulin pump therapy. DISCUSSION: Canagliflozin is a selective inhibitor of SGLT2, approved by the FDA in 2013 to lower blood sugar in adults with T2D. Canagliflozin promotes significant glycosuria, allowing for improvement in glycemic control (3). In a study on the use of SGLT2 inhibitors in patients with T1D, out of 42 patients at the initiation of the study, two withdrew early after developing diabetic ketoacidosis, despite lower than expected plasma glucose concentrations (2). In the current case of a patient with T1D taking canagliflozin while on an insulin pump, she developed symptoms of diabetic ketoacidosis without the findings of elevated serum blood glucose. Conclusions: SGLT2 inhibitors may mask the common symptom of hyperglycemia in DKA by inducing glycosuria. Patients who are started on SGLT2 inhibitors should be instructed to seek medical attention if they begin to experience the symptoms of diabetic ketoacidosis and healthcare professionals should consider diabetic ketoacidosis as a diagnosis in patients taking an SGLT2 inhibitor, regardless of serum glucose.