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

NCT ID: NCT02610088

Last Updated: 2018-09-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2018-09-30

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.

Conditions

Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Dapagliflozin

Dapagliflozin will be started in patient with type 2 diabetes mellitus

Group Type: ACTIVE_COMPARATOR

Dapagliflozin

Intervention Type: DRUG

Dapagliflozin 10 mg, orally once daily at any time of day with or without food. If HbA1c does not decrease by \> 0.4% at 12 week, rescue therapy (sitagliptin 100 mg) can be added at investigator's discretion.

Gliclazide

Gliclazide will be started in patient with type 2 diabetes mellitus

Group Type: ACTIVE_COMPARATOR

Gliclazide

Intervention Type: DRUG

Gliclazide MR 30 mg, orally once daily at any time of day with or without food. If HbA1c does not decrease by \> 0.4% at 12 week, rescue therapy (gliclazide MR 30 mg) can be added at investigator's discretion.

Interventions

Dapagliflozin

Dapagliflozin 10 mg, orally once daily at any time of day with or without food. If HbA1c does not decrease by \> 0.4% at 12 week, rescue therapy (sitagliptin 100 mg) can be added at investigator's discretion.

Intervention Type: DRUG

Gliclazide

Gliclazide MR 30 mg, orally once daily at any time of day with or without food. If HbA1c does not decrease by \> 0.4% at 12 week, rescue therapy (gliclazide MR 30 mg) can be added at investigator's discretion.

Intervention Type: DRUG

Other Intervention Names

Forxiga; Diamicron MR

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seoul National University Bundang Hospital

OTHER

Sponsor Role: lead

Responsible Party

Soo Lim

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Countries

South Korea

Other Identifiers

B-1507/307-006

Identifier Type: -

Identifier Source: org_study_id