Assessment of Dapagliflozin Effect on Diabetic Endothelial Dysfunction of Brachial Artery
Status:
Completed
Trial end date:
2019-03-01
Target enrollment:
Participant gender:
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.