Effects of Baseline Blood Pressure and Low-Density Lipoprotein Cholesterol on Safety and Efficacy of Canagliflozin in Japanese Patients with Type 2 Diabetes Mellitus

INTRODUCTION Sodium glucose co-transporter 2 inhibitors decrease hemoglobin A1c (HbA1c) and blood pressure (BP) and slightly increase low-density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes mellitus (T2DM). The effects of baseline BP and LDL-C on the safety and efficacy of canagliflozin in patients were analyzed post hoc in a phase III study. METHODS Japanese patients with T2DM were classified by baseline systolic BP (SBP) of <130 or ≥130 mmHg, diastolic BP (DBP) of <80 or ≥80 mmHg, and LDL-C of <120 or ≥120 mg/dL. Canagliflozin was administered daily to patients for 52 weeks at doses of either 100 mg (n = 584) or 200 mg (n = 715). The effects of canagliflozin on the incidence of adverse events (AEs), BP, and LDL-C were evaluated. RESULTS No clear differences were observed in overall safety among the subgroups classified by baseline SBP, DBP, or LDL-C, except for a slight imbalance in AEs associated with volume depletion with 200 mg of canagliflozin. The decrease in mean SBP and DBP was evident in subgroups with baseline SBP ≥130 mmHg and DBP ≥80 mmHg. Mean LDL-C was decreased in subgroups with baseline LDL-C ≥120 mg/dL at both canagliflozin doses, and they were slightly increased, but did not exceed 120 mg/dL in subgroups with baseline LDL-C <120 mg/dL. The changes in HbA1c and body weight from those observed at baseline were not different between subgroups classified by SBP, DBP, and LDL-C at either dose. CONCLUSION The present post hoc analysis indicates that canagliflozin is well tolerated irrespective of baseline BP and LDL-C in patients with T2DM. TRIAL REGISTRATION ClinicalTrials.gov identifier, NCT01387737. FUNDING Mitsubishi Tanabe Pharma Corporation.