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

Nobuya Inagaki, Maki Goda, Shoko Yokota, Nobuko Maruyama, Hiroaki Iijima, Nobuya Inagaki, Maki Goda, Shoko Yokota, Nobuko Maruyama, Hiroaki Iijima

Abstract

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.

Keywords: Blood pressure; Canagliflozin; Low-density lipoprotein cholesterol (LDL-C); Sodium glucose co-transporter 2 (SGLT2) inhibitor; Type 2 diabetes mellitus; Volume depletion.

Figures

Fig. 1
Fig. 1
Changes in SBP (a) and DBP (b) over time in subgroups classified by BP. Each point and bar represent mean and standard deviation, respectively. BP blood pressure, DBP diastolic blood pressure, SBP systolic blood pressure
Fig. 2
Fig. 2
Change in LDL-C over time in subgroups classified by LDL-C. Each point and bar represent mean and standard deviation, respectively. LDL-C low-density lipoprotein cholesterol

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