title: Effects of Baseline Blood Pressure and Low-Density Lipoprotein Cholesterol on Safety and Efficacy of Canagliflozin in Japanese Patients with Type 2 Diabetes Mellitus.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  The present post hoc analysis indicates that canagliflozin is well tolerated irrespective of baseline BP and LDL-C in patients with T2DM.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier, NCT01387737.
  
  
  BACKGROUND
  Mitsubishi Tanabe Pharma Corporation.
authors.affiliation: Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan. gouda.maki@mm.mt-pharma.co.jp.
authors.forename: Maki
authors.initials: M
authors.lastname: Goda
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Yokota
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Maruyama
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iijima
mesh_terms: D000368:Aged; D044466:Asian People; D001794:Blood Pressure; D001835:Body Weight; D000068896:Canagliflozin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D007564:Japan; D008297:Male; D008875:Middle Aged; D051297:Sodium-Glucose Transporter 2
chemical_list: D000068896:Canagliflozin; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D051297:Sodium-Glucose Transporter 2
keywords: Blood pressure; Canagliflozin; Low-density lipoprotein cholesterol (LDL-C); Sodium glucose co-transporter 2 (SGLT2) inhibitor; Type 2 diabetes mellitus; Volume depletion