PMID- 25329038
OWN - NLM
STAT- MEDLINE
DCOM- 20150922
LR  - 20220408
IS  - 1751-7176 (Electronic)
IS  - 1524-6175 (Print)
IS  - 1524-6175 (Linking)
VI  - 16
IP  - 12
DP  - 2014 Dec
TI  - Effect of canagliflozin on blood pressure and adverse events related to osmotic 
      diuresis and reduced intravascular volume in patients with type 2 diabetes 
      mellitus.
PG  - 875-82
LID - 10.1111/jch.12425 [doi]
AB  - The effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on 
      blood pressure (BP) and osmotic diuresis- and intravascular volume 
      reduction-related adverse events (AEs) were evaluated using pooled data from four 
      placebo-controlled, phase 3 studies in patients with type 2 diabetes mellitus 
      (T2DM; N=2313). At baseline, 1332 (57.6%) patients were taking an 
      antihypertensive medication. Canagliflozin 100 mg and 300 mg provided reductions 
      (95% confidence interval [CI]) from baseline in systolic BP (SBP) compared with 
      placebo (-4.3 mm Hg [-5.0 to -3.5], -5.0 mm Hg [-5.8 to -4.2], and -0.3 mm Hg 
      [-1.2 to 0.5], respectively) and in diastolic BP (DBP; -2.5 mm Hg [-2.9 to -2.0], 
      -2.4 mm Hg [-2.9 to -1.9], and -0.6 mm Hg [-1.1 to -0.02], respectively). 
      Placebo-subtracted reductions (95% CI) in SBP with canagliflozin 100 mg and 300 
      mg were -4.0 mm Hg (-5.1 to -2.8) and -4.7 mm Hg (-5.8 to -3.5) and reductions in 
      DBP were -1.9 mm Hg (-2.6 to -1.2) and -1.9 mm Hg (-2.6 to -1.1), respectively. 
      Compared with the overall population, patients with elevated baseline SBP (>/=140 
      mm Hg) had numerically greater absolute SBP reductions (95% CI) with 
      canagliflozin 100 mg and 300 mg and placebo (-12.8 mm Hg [-15.2 to -10.5], -14.2 
      mm Hg [-16.4 to -12.0], and -6.8 mm Hg [-9.1 to -4.5], respectively). Numerically 
      greater DBP reductions were seen in patients with DBP >/=90 mm Hg at baseline (-5.9 
      mm Hg [-8.2 to -3.6], -9.0 mm Hg [-11.1 to -6.9], and -7.4 mm Hg [-9.6 to -5.1], 
      respectively). In patients with elevated SBP at baseline, placebo-subtracted 
      reductions (95% CI) in SBP with canagliflozin 100 mg and 300 mg were -6.0 mm Hg 
      (-9.1 to -2.9) and -7.4 mm Hg (-10.4 to -4.4), respectively. Placebo-subtracted 
      changes in DBP were 1.5 mm Hg (-1.6 to 4.5) and -1.6 mm Hg (-4.5 to 1.2), 
      respectively, in those with elevated DBP at baseline. Canagliflozin 100 mg and 
      300 mg were associated with increased incidence of osmotic diuresis-related AEs 
      (e.g., pollakiuria [increased urine volume] and polyuria [increased urine 
      frequency]) vs placebo (6.7%, 5.6%, and 0.8%). The incidence of intravascular 
      volume reduction-related AEs (eg, orthostatic hypotension and postural dizziness) 
      was low across groups (1.2%, 1.3%, and 1.1%). In summary, canagliflozin was 
      associated with reduced BP in patients with T2DM across a range of baseline BPs, 
      with increased incidence of AEs related to osmotic diuresis but not intravascular 
      volume reduction.
CI  - Copyright (c) 2014 Wiley Periodicals, Inc.
FAU - Weir, Matthew R
AU  - Weir MR
AD  - Division of Nephrology, Department of Medicine, University of Maryland School of 
      Medicine, Baltimore, MD.
FAU - Januszewicz, Andrzej
AU  - Januszewicz A
FAU - Gilbert, Richard E
AU  - Gilbert RE
FAU - Vijapurkar, Ujjwala
AU  - Vijapurkar U
FAU - Kline, Irina
AU  - Kline I
FAU - Fung, Albert
AU  - Fung A
FAU - Meininger, Gary
AU  - Meininger G
LA  - eng
SI  - ClinicalTrials.gov/NCT01081834
SI  - ClinicalTrials.gov/NCT01106625
SI  - ClinicalTrials.gov/NCT01106677
SI  - ClinicalTrials.gov/NCT01106690
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141020
PL  - United States
TA  - J Clin Hypertens (Greenwich)
JT  - Journal of clinical hypertension (Greenwich, Conn.)
JID - 100888554
RN  - 0 (Glucosides)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 0 (Thiophenes)
RN  - 0SAC974Z85 (Canagliflozin)
SB  - IM
MH  - Aged
MH  - Blood Pressure/*drug effects
MH  - Blood Pressure Determination
MH  - Canagliflozin
MH  - Diabetes Mellitus, Type 2/*drug therapy/physiopathology
MH  - Diuresis
MH  - Female
MH  - Glucosides/adverse effects/*therapeutic use
MH  - Humans
MH  - Hypertension/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Sodium-Glucose Transporter 2/*drug effects
MH  - Thiophenes/adverse effects/*therapeutic use
PMC - PMC8031563
EDAT- 2014/10/21 06:00
MHDA- 2015/09/24 06:00
PMCR- 2014/10/20
CRDT- 2014/10/21 06:00
PHST- 2014/07/02 00:00 [received]
PHST- 2014/08/22 00:00 [revised]
PHST- 2014/08/25 00:00 [accepted]
PHST- 2014/10/21 06:00 [entrez]
PHST- 2014/10/21 06:00 [pubmed]
PHST- 2015/09/24 06:00 [medline]
PHST- 2014/10/20 00:00 [pmc-release]
AID - JCH12425 [pii]
AID - 10.1111/jch.12425 [doi]
PST - ppublish
SO  - J Clin Hypertens (Greenwich). 2014 Dec;16(12):875-82. doi: 10.1111/jch.12425. 
      Epub 2014 Oct 20.