Effect of Dapagliflozin on Vascular Functions in Patients With Type 2 Diabetes Compared to Gliclazide

Seoul National University

Status and phase

Completed

Phase 4

Conditions

Diabetes

Treatments

Drug: Gliclazide

Drug: Dapagliflozin

Study type

Interventional

Funder types

Other

Identifiers

NCT02610088

B-1507/307-006

Details and patient eligibility

About

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

Full 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.

Enrollment

32 patients

Sex

All

Ages

40 to 70 years old

Volunteers

No Healthy Volunteers

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