Diabetic Ketoacidosis and Related Events in the Canagliflozin Type 2 Diabetes Clinical Program

OBJECTIVE This study assessed the incidence of serious adverse events of diabetic ketoacidosis (DKA) among patients with type 2 diabetes treated with canagliflozin. RESEARCH DESIGN AND METHODS All serious adverse events of DKA and related events (ketoacidosis, metabolic acidosis, and acidosis) from 17,596 patients from randomized studies of canagliflozin through 11 May 2015 were analyzed. RESULTS Serious adverse events of DKA and related events were reported in 12 patients (0.07%), including 4 (0.07%), 6 (0.11%), and 2 (0.03%) treated with canagliflozin 100 and 300 mg and comparator, respectively; corresponding incidence rates were 0.522, 0.763, and 0.238 per 1,000 patient-years, respectively. Most patients with DKA and related events had a blood glucose >300 mg/dL (16.7 mmol/L) at presentation of DKA, were on insulin, and had DKA-precipitating factors, including some with type 1 diabetes/latent autoimmune diabetes of adulthood. CONCLUSIONS DKA and related events occurred at a low frequency in the canagliflozin type 2 diabetes program, with an incidence consistent with limited existing observational data in the general population with type 2 diabetes.