The Effect of Vildagliptin Based Treatment Versus Sulfonylurea on Glycemic Variability, Oxidative Stress, GLP-1, and Endothelial Function in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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The effect of vildagliptin based treatment versus sulfonylurea based treatment on glycemic variability, oxidative stress, and endothelial function in patients with type 2 diabetes.

Detailed Description
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Recently, improved understanding of the incretin effect on the pathophysiology of type 2 diabetes has led to development of new agent for hypoglycemic therapy. Vildagliptin is a potent and highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor that augments the active glucagon-like peptide(GLP)-1 concentration, increases insulin secretion and improves glucose tolerance. Vildagliptin has a similar glucose lowering effect, but lower hypoglycemic events, as compared to glimepiride. Vildagliptin could improve not only the mean glycemic control but also 24 hour glycemic fluctuation by restoring the physiologic pattern of insulin and glucagon secretion. Furthermore, decreased postprandial glycemic excursion might reduce the oxidative stress markers and improve endothelial dysfunction. Those effects might be amplified in Asian patients because of prominent early phase insulin secretory defects accompanied with relatively less degree of insulin resistance. In addition, GLP-1 and GLP-1 analogues exert direct beneficial effects on endothelium-dependent vasodilatation. Therefore DPP-4 inhibitors may directly improve endothelial dysfunction. Based on this assumption, this research will focus on the effect of vildagliptin on glycemic variability, oxidative stress markers and endothelial cell function compared to long acting sulfonylurea glimepiride in type 2 diabetic patients with inadequate glycemic control on metformin.

Official Title
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The Effect of Vildagliptin Based Treatment Versus Sulfonylurea on Glycemic Variability, Oxidative Stress, GLP-1, and Endothelial Function in Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Add Vildagliptin
* Drug: Add Glimepiride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetic patients with hemoglobin A1c levels within the range 7% - 10%

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vildagliptin + Metformin<br>Adding Vildagliptin to metformin users | Drug: Add Vildagliptin<br>* Adding Vildagliptin 50 mg bid to patients with type 2 diabetes mellitus being treated with metformin 500-1000mg bid per day who had hemoglobin A1c of 7.0-10.0%<br>|
| Active Comparator: Glimepiride + Metformin<br>Adding Glimepiride to metformin users | Drug: Add Glimepiride<br>* Adding Glimepiride 2mg to patients with type 2 diabetes mellitus being treated with metformin 500-1000mg bid per day who had hemoglobin A1c of 7.0-10.0%<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean amplitude of glycemic excursion(MAGE) for 12 weeks(12weeks - 0 week). | To compare the effect of vildagliptin based treatment for 12 weeks on glycemic variability with sulfonylurea using continuous glucose monitoring system(CGMS). | 0 week and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in oxidative stress markers and inflammatory markers at 12 weeks. Change from baseline in endothelial cell function at 12 weeks. | To evaluate the change of oxidative stress markers and inflammatory markers from baseline. To evaluate the change of endothelial cell function using high-resolution ultrasonography to measure brachial artery flow-mediated dilation (FMD) from baseline. | 0 week and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucose variability, Oxidative stress, Endothelial cell function