Diabetic Ketoacidosis With Canagliflozin, a Sodium–Glucose Cotransporter 2 Inhibitor, in Patients With Type 1 Diabetes

Abstract

Objective To assess the incidence of serious adverse events (AEs) of diabetic ketoacidosis (DKA) with canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as an add-on to insulin in adults with type 1 diabetes. Research design and methods In this 18-week, randomized, double-blind, phase 2 study, patients (N = 351; HbA1c 7.0-9.0% [53-75 mmol/mol]) on multiple daily insulin injections or continuous subcutaneous insulin infusion received canagliflozin 100 or 300 mg or placebo once daily. The incidence of ketone-related AEs, defined as any event from a prespecified list of preferred terms (i.e., acidosis, blood ketone body increased, blood ketone body present, DKA, diabetic ketoacidotic hyperglycemic coma, ketoacidosis, ketonemia, ketonuria, ketosis, metabolic acidosis, urine ketone body present), including serious AEs of DKA, was assessed based on AE reports. Results At week 18, the incidence of any ketone-related AE with canagliflozin 100 and 300 mg was 5.1% (n = 6 of 117) and 9.4% (n = 11 of 117), respectively; no patients in the placebo group experienced a ketone-related AE. The incidence of serious AEs of DKA was 4.3% (n = 5 of 117) with canagliflozin 100 mg and 6.0% (n = 7 of 117) with canagliflozin 300 mg; all serious events occurred in the presence of circumstances that are known to potentially precipitate DKA (e.g., infection, insulin pump failure). Among the 12 patients with a serious AE of DKA, blood glucose levels ranged from 9.4 to >44.4 mmol/L (170 to >800 mg/…