title: 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.
abstract: 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) × 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).
  
  
  
  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.
  
  
  
  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 × 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.
  
  
  
  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).
authors.affiliation: Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA. mpfeifer@its.jnj.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Pfeifer
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, 122 Founders Building, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Townsend
authors.affiliation: Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
authors.affiliation: Janssen Research & Development, LLC, 920 US Highway 202 South, Raritan, NJ, 08869, USA.
authors.forename: Ujjwala
authors.initials: U
authors.lastname: Vijapurkar
authors.affiliation: Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Ren
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D000068896:Canagliflozin / Q000009:adverse effects / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013997:Time Factors; D016896:Treatment Outcome; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000068896:Canagliflozin
keywords: Ambulatory blood pressure monitoring; Blood pressure; Canagliflozin; Double product; Mean arterial pressure; Pulse pressure; Sodium glucose co-transporter 2 (SGLT2) inhibitor; Type 2 diabetes