Clinical trial NCT02610088: Effect of Dapagliflozin on Vascular Functions in Patients With Type 2 Diabetes Compared to Gliclazide
Official title: Effect of Dapagliflozin, a Sodium Glucose Co-transporter 2 Inhibitor, on Vascular Functions in Patients With Type 2 Diabetes Compared to Gliclazide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes
Keywords: Diabetes
Atherosclerosis
Cardiovascular disease
Endothelial dysfunction
Vascular function
Dapagliflozin
Gliclazide
Lead sponsor: Seoul National University Bundang Hospital
Sponsor class: OTHER
First posted: 2015-11-20
Enrollment: 32
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators set up a clinical trial to compare effect of dapagliflozin, a sodium glucose co-transporter 2 inhibitor, with gliclazide on vascular function in patients with type 2 diabetes

Detailed description: Obesity, and especially visceral/abdominal adiposity, is associated with diabetes and increased cardiovascular risk. In previous randomized, double-blind, placebo-controlled study, dapagliflozin reduced total body weight, predominantly by reducing fat mass, visceral adipose tissue and sc adipose tissue in type 2 diabetes. This study supported that caloric loss from glycosuria, and not fluid loss, was principally responsible for decrease in total body weight and fat mass. In fact, there have been several reports proving that inhibition of SGLT2 improves β-cell function and reduces body weight and blood pressure. However, effects of SGLT2 inhibitors on lipid profiles have not been decided yet in patients with type 2 diabetes. Furthermore, there are few data to demonstrate the effects of SGLT2 inhibitors on CV risk.

Many systems and pathways are involved in development of atherosclerosis in the arterial wall. Accumulating evidence suggests that endothelial dysfunction plays an important role particularly in the first stage of atherogenesis in patients with diabetes. Approaches designed to improve endothelial function may therefore have additional therapeutic value in the prevention and treatment of atherosclerotic disease. Endothelial dysfunction is related to decreased production and bioavailability of nitric oxide (NO). Endothelial function was measured through several circulating biomarker such as NO, endothelin-1 or non-invasive techniques such as flow-mediated dilation (FMD), skin laser doppler. Among them, FMD is known to as the optimal tool. In addition, several noninvasive techniques including measurement of the ankle-brachial index (ABI), carotid intima-media thickness (IMT) and pulse wave velocity (PWV) have been used for evaluation of atherosclerosis.

If a participant's HbA1c dose not decreas by \>0.4% at 12 weeks, rescue therapy can be added at the investigator's discretion.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes with HbA1c ≥ 7.5% at screening visit
* Male or female between 40 and 70 years of age
* Patients taking metformin (≥ 1000 mg or maximum tolerated dose) for more than 3 months
* BMI ≥23 kg/m²
* Estimated GFR ≥ 60 ml/min/1.73m²

Exclusion Criteria:

* Patients with acute coronary syndrome within 3 months prior to screening visit
* Pregnant or breast feeding women or reproductive-age women who refuse contraception
* Type 1 diabetes, gestational diabetes, or diabetes with secondary cause
* Chronic hepatitis B or C (except healthy carrier of HBV), liver disease (AST/ALT \> 3-fold the upper limit of normal)
* Cancer within 5 years (except squamous cell cancer, cervical cancer, thyroid cancer with appropriate treatment) except thyroid cancer or carcinoma in situ
* Other clinical trial within 30 days
* Alcohol abuse
* Contraindication to SGLT2 inhibitors or sulfonylurea

Primary outcomes:
measure: Vascular function assessed by Flow-mediated vasodilation (FMD)
timeFrame: 24weeks
Secondary outcomes:
measure: Change of blood pressure
timeFrame: 24weeks
measure: Lipid metabolism assessed by triglyceride, low density lipoprotein-cholesterol and high density lipoprotein-cholesterol
timeFrame: 24weeks
measure: Inflammatory markers assessed by hsCRP
timeFrame: 24weeks
measure: Change of body composition assessed by bioelectrical impedance analysis (BIA) methods
timeFrame: 24weeks
measure: Glucose metabolism assessed by glycated hemoglobin and fasting plasma glucose
timeFrame: 24weeks
measure: Microcirculation assessed by laser doppler
timeFrame: 24weeks
measure: Vascular health assessment by pulse wave velocity (PWV)
timeFrame: 24weeks
measure: Vascular health assessment by Ankle-brachial index (ABI)
timeFrame: 24weeks
measure: Carotid intima-media thickness (cIMT) assessed by ultrasound
timeFrame: 24weeks
Other outcomes:
Locations:
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi
Study officials:
References: