Assessment of Dapagliflozin Effect on Diabetic Endothelial Dysfunction of Brachial Artery
Condition: Diabetes Mellitus, Type 2; Coronary Artery Disease; Carotid Artery Diseases
MeSH terms: Carotid Artery Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      Background Endothelial dysfunction is one of the early events in atherosclerotic plaque
      development. It is characterized by an increased ratio of substances with vasoconstrictive,
      pro-thrombotic, and proliferative properties over substances with vasolidatory,
      antithrombogenic and antimitogenic properties. Endothelial dysfunction is also associated
      with high-risk patients with coronary artery disease. Hyperglycemia, obesity, hypertension
      and fat mass also impair the endothelium by increasing the expression of cytokines,
      inflammatory markers and vascular markers.

      Hypothesis Administration of dapagliflozin in addition to metformin background with clinical
      or subclinical cardiovascular atherosclerotic disease improves endothelial function when
      compared to those using glibenclamide in addition to metformin.

      Objectives Evaluate the effect of dapagliflozin vs glibenclamide on a metformin background on
      endothelial function in patients with clinical or subclinical cardiovascular atherosclerotic
      disease and poorly controlled diabetes.

      Enpoints Prymary Change in flow mediated dilation (FMD) and its related endpoint (FMD post
      reperfusion lesion) between the randomization visit and over 12 weeks of treatment.

      Secondary Change in plasma nitric oxide, isoprostane, ICAM-1, VCAM-1, ET-1, leptin,
      adiponectin, C-reactive protein, TNF- α, interleukin-6, interleukin-2, weight and body
      composition (% of fat mass and % free fat mass) at the randomization visit and over 12 weeks
      of treatment.

      3

      Design Randomized, parallel-group, comparative, prospective clinical study. The study is
      divided in two phases: Run-in and Randomization. In the former phase, which must have the
      maximum period of 16 weeks, patients will visit the outpatient to adjust metformin and blood
      pressure medications. After run-in phase, patients that fulfill inclusion criteria will
      perform an ambulatory blood pressure monitoring (ABPM) in order to asses BP; body composition
      will be assessed by dual x-ray absorptiometry (DXA); endothelial function as assessed by flow
      mediated dilation and vascular cytokines. Patients will by randomized to dapagliflozin or
      glibenclamide on a metformin background. After 12 weeks, the ABPM, DXA and endothelial
      function will be assessed.
    


Intervention name(s): Dapagliflozin 10 mg; Glibenclamide 5 mg
Intervention type(s): Drug; Drug
Intervention description(s): Dapagliflozin 10 mg in addition to Metformin 1500 mg/day; Glibenclamide 5 mg in addition to Metformin 1500 mg/day
Other intervention name(s): Farxiga; Daonil, Glyburide
Intervention MeSH terms: Dapagliflozin; Glyburide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Dapagliflozin; Glibenclamide; Endothelial Function; Vascular Endothelial Cells; Flow Mediated Dilation