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.