PMID- 28241822
OWN - NLM
STAT- MEDLINE
DCOM- 20171016
LR  - 20181227
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 16
IP  - 1
DP  - 2017 Feb 27
TI  - Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood 
      pressure and markers of arterial stiffness in patients with type 2 diabetes 
      mellitus: a post hoc analysis.
PG  - 29
LID - 10.1186/s12933-017-0511-0 [doi]
LID - 29
AB  - BACKGROUND: Physiologic determinants, such as pulse pressure [difference between 
      systolic blood pressure (SBP) and diastolic BP (DBP)], mean arterial pressure 
      (2/3 DBP + 1/3 SBP), and double product [beats per minute (bpm) x SBP], are 
      linked to cardiovascular outcomes. The effects of canagliflozin, a sodium glucose 
      co-transporter 2 (SGLT2) inhibitor, on pulse pressure, mean arterial pressure, 
      and double product were assessed in patients with type 2 diabetes mellitus 
      (T2DM). METHODS: This post hoc analysis was based on pooled data from four 
      26-week, randomized, double-blind, placebo-controlled studies evaluating 
      canagliflozin in patients with T2DM (N = 2313) and a 6-week, randomized, 
      double-blind, placebo-controlled, ambulatory BP monitoring (ABPM) study 
      evaluating canagliflozin in patients with T2DM and hypertension (N = 169). 
      Changes from baseline in SBP, DBP, pulse pressure, mean arterial pressure, and 
      double product were assessed using seated BP measurements (pooled studies) or 
      averaged 24-h BP assessments (ABPM study). Safety was assessed based on adverse 
      event reports. RESULTS: In the pooled studies, canagliflozin 100 and 300 mg 
      reduced SBP (-4.3 and -5.0 vs -0.3 mmHg) and DBP (-2.5 and -2.4 vs -0.6 mmHg) 
      versus placebo at week 26. Reductions in pulse pressure (-1.8 and -2.6 vs 
      0.2 mmHg), mean arterial pressure (-3.1 and -3.3 vs -0.5 mmHg), and double 
      product (-381 and -416 vs -30 bpm x mmHg) were also seen with canagliflozin 100 
      and 300 mg versus placebo. In the ABPM study, canagliflozin 100 and 300 mg 
      reduced mean 24-h SBP (-4.5 and -6.2 vs -1.2 mmHg) and DBP (-2.2 and -3.2 vs 
      -0.3 mmHg) versus placebo at week 6. Canagliflozin 300 mg provided reductions in 
      pulse pressure (-3.3 vs -0.8 mmHg) and mean arterial pressure (-4.2 vs -0.6 mmHg) 
      compared with placebo, while canagliflozin 100 mg had more modest effects on 
      these parameters. Canagliflozin was generally well tolerated in both study 
      populations. CONCLUSIONS: Canagliflozin improved all three cardiovascular 
      physiologic markers, consistent with the hypothesis that canagliflozin may have 
      beneficial effects on some cardiovascular outcomes in patients with T2DM. Trial 
      registration ClinicalTrials.gov Identifier: NCT01081834 (registered March 2010); 
      NCT01106677 (registered April 2010); NCT01106625 (registered April 2010); 
      NCT01106690 (registered April 2010); NCT01939496 (registered September 2013).
FAU - Pfeifer, Michael
AU  - Pfeifer M
AD  - Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 
      08560, USA. mpfeifer@its.jnj.com.
FAU - Townsend, Raymond R
AU  - Townsend RR
AD  - Perelman School of Medicine, University of Pennsylvania, 122 Founders Building, 
      3400 Spruce Street, Philadelphia, PA, 19104, USA.
FAU - Davies, Michael J
AU  - Davies MJ
AD  - Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 
      08560, USA.
FAU - Vijapurkar, Ujjwala
AU  - Vijapurkar U
AD  - Janssen Research & Development, LLC, 920 US Highway 202 South, Raritan, NJ, 
      08869, USA.
FAU - Ren, Jimmy
AU  - Ren J
AD  - Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 
      08560, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01081834
SI  - ClinicalTrials.gov/NCT01106625
SI  - ClinicalTrials.gov/NCT01106677
SI  - ClinicalTrials.gov/NCT01939496
SI  - ClinicalTrials.gov/NCT01106625
SI  - ClinicalTrials.gov/NCT01106690
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20170227
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (SLC5A2 protein, human)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0SAC974Z85 (Canagliflozin)
SB  - IM
MH  - Aged
MH  - Blood Pressure/*drug effects
MH  - Blood Pressure Monitoring, Ambulatory
MH  - Canagliflozin/adverse effects/*therapeutic use
MH  - Diabetes Mellitus, Type 2/diagnosis/*drug therapy/metabolism/physiopathology
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Hypertension/diagnosis/*physiopathology
MH  - Hypoglycemic Agents/adverse effects/*therapeutic use
MH  - Kidney Tubules, Proximal/*drug effects/metabolism
MH  - Male
MH  - Middle Aged
MH  - Sodium-Glucose Transporter 2/metabolism
MH  - *Sodium-Glucose Transporter 2 Inhibitors
MH  - Time Factors
MH  - Treatment Outcome
MH  - Vascular Stiffness/*drug effects
PMC - PMC5327537
OTO - NOTNLM
OT  - Ambulatory blood pressure monitoring
OT  - Blood pressure
OT  - Canagliflozin
OT  - Double product
OT  - Mean arterial pressure
OT  - Pulse pressure
OT  - Sodium glucose co-transporter 2 (SGLT2) inhibitor
OT  - Type 2 diabetes
EDAT- 2017/03/01 06:00
MHDA- 2017/10/17 06:00
PMCR- 2017/02/27
CRDT- 2017/03/01 06:00
PHST- 2016/11/29 00:00 [received]
PHST- 2017/02/05 00:00 [accepted]
PHST- 2017/03/01 06:00 [entrez]
PHST- 2017/03/01 06:00 [pubmed]
PHST- 2017/10/17 06:00 [medline]
PHST- 2017/02/27 00:00 [pmc-release]
AID - 10.1186/s12933-017-0511-0 [pii]
AID - 511 [pii]
AID - 10.1186/s12933-017-0511-0 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2017 Feb 27;16(1):29. doi: 10.1186/s12933-017-0511-0.