title: A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation.
abstract: The sodium-glucose cotransporter 2 inhibitor, dapagliflozin, has been shown to improve diabetic control and reduce blood pressure in patients with type 2 diabetes mellitus. Its effects on micro- and macrovascular structure and function have not yet been reported.
  
  
  
  This was a prospective, single-centre, placebo-controlled, double-blind, randomised crossover phase IIIb study conducted between March 2014 and February 2015. After a 4-week run-in/washout phase, patients (N = 59) received 6 weeks of either dapagliflozin 10 mg or placebo once daily. They then underwent a 1-week washout before crossing over to the other treatment. Changes in retinal capillary flow (RCF) and arteriole remodelling were evaluated using scanning laser Doppler flowmetry, while micro- and macrovascular parameters in the systemic circulation were assessed using pulse wave analysis.
  
  
  
  Six weeks of dapagliflozin treatment resulted in improvements in diabetes control, including blood glucose and insulin resistance, and reduced office and 24-h ambulatory blood pressure values. RCF decreased from 324 AU at baseline to 308 AU after treatment with dapagliflozin (p = 0.028), while there was little difference after the placebo (318 AU; p = 0.334). Furthermore, the arteriole remodelling that was seen after the placebo phase was not evident after the dapagliflozin phase. Central systolic and diastolic blood pressure values were significantly lower after 6 weeks of dapagliflozin, by 3.0 and 2.2 mmHg, respectively (p = 0.035 and 0.020, respectively vs. baseline).
  
  
  
  Six weeks of dapagliflozin treatment resulted in numerous beneficial effects. In addition to achieving superior diabetes control and blood pressure, parameters associated with the early stages of vascular remodelling were also improved. Trial registration http://www.clinicaltrials.gov (NCT02383238).
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Ott
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054, Erlangen, Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Jumar
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054, Erlangen, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Striepe
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054, Erlangen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Friedrich
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054, Erlangen, Germany.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Karg
authors.affiliation: Institute for Pharmacology and Preventive Medicine, Mahlow, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bramlage
authors.affiliation: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054, Erlangen, Germany. roland.schmieder@uk-erlangen.de.
authors.forename: Roland E
authors.identifier: 0000-0003-2356-5883
authors.initials: RE
authors.lastname: Schmieder
mesh_terms: D000368:Aged; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D055806:Microvessels / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D011446:Prospective Studies; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C529054:dapagliflozin
keywords: Arterial remodelling; Blood pressure; Insulin resistance; Pulse wave analysis; SGLT2 inhibitors; Scanning laser Doppler flowmetry, vascular protection