Effect of Adding Vildagliptin vs Glimepiride to Metformin on Inflammation's Markers in Type-2 Diabetic Patients With CAD

Study Overview
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Brief Summary
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The aim of this study is to evaluate the effect of adding Vildagliptin versus Glimepiride to Metformin on markers of inflammation, thrombosis, and atherosclerosis in diabetic patients with symptomatic Coronary artery diseases. The pre-specified established biological markers of inflammation, thrombosis, and atherosclerosis will include: Interleukin 1 beta (IL-1 beta)), hs-CRP, Atherogenic index and coronary risk index, Lipid profile. and adiponectin levels..

Detailed Description
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The study is designed as a single-center, randomized, double-blinded, clinical trial to provide evidence on the effects of vildagliptin on key biomarkers of atherothrombosis and inflammation. The investigators plan to prospectively enroll 80 patients with proven coronary artery disease ,Diabetes type2 and randomize them in a 1:1 ratio to either vildagliptin-metformin therapy (n=40) or glimepiride /metformin therapy (n=40). All participants agreed to take part in this clinical study and provide informed consent. Patients with Coronary artery diseases.and uncontrolled Diabetes type2 who's taking metformin only will be enrolled (n=80) from endocrinology clinic at Alexandria Armed Forces hospital. Complete physical, laboratory, radiological assessment will be done for all patients to exclude any signs of inflammation or thrombosis. Serum samples will be collected for measuring the biomarkers. All enrolled patients will be mentioned as two groups; Group I (n=40) are patients who the endocrinologist prescribed them vildagliptin plus their metformin to control their blood sugar level. Group II (n=40) are patients who the endocrinologist prescribed them glimepiride plus their metformin. All patients will be followed up during 3 months' period. At the end of 3 months on the new regimen, steps 4 and 5 will be repeated. Statistical tests appropriate to the study design will be conducted to evaluate the significance of the results. Measuring outcome: The primary outcome is the change of serum levels of the measured inflammatory markers after 3 months. Results, conclusion, discussion and recommendations will be given.

Official Title
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The Effect of Adding Vildagliptin Versus Glimepiride to Metformin on Markers of Inflammation, Thrombosis, and Atherosclerosis in Diabetic Patients With Symptomatic Coronary Artery Diseases

Conditions
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Coronary Artery Disease, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Vildagliptin 50 mg Oral Tablet
* Drug: Metformin 1000 mg Oral Tablet
* Drug: Glimepiride upto 4 mg Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients with Type II-diabetes mellitus on metformin who are planned to be managed with vildagliptin or glimepiride plus metformin at the time of inclusion. Symptomatic Coronary Artery Diseases. (>30 days). Exclusion Criteria: Hepatic impairment. Active malignancy. Planned surgical intervention. Any signs of hypersensitivity or contraindication to study drugs developed. Any patient with any signs of active infection or thrombosis at the time of assessment. Addition of any antidiabetic medications or insulin during follows up. Chronic inflammatory disease (i.e. inflammatory bowel disease, lupus, inflammatory arthritis, rheumatoid arthritis) or chronic infection (i.e. chronic diabetic foot infection). Clinically advanced congestive heart failure - New York Heart Association III-IV Severe left ventricular dysfunction (LVEF<30%) with New York Heart Association II or any New York Heart Association class with documented recent heart failure decompensation (<3 months) Severe stable cardiac angina Community Competence Scale III - IV or Unstable angina Pregnancy, lactation or child-bearing potential.

Ages Eligible for Study
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Minimum Age: 25 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
Interventional Model Description: All enrolled patients will be mentioned as two groups; Group I (n=40) are patients who the endocrinologist prescribed them vildagliptin plus their metformin to control their blood sugar level. Group II (n=40) are patients who the endocrinologist prescribed them glimepiride plus their metformin.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vildagliptin / metformin<br>Group I (n=40) are patients who are taking vildagliptin 50 mg oral tablet plus their metformin1000 mg oral tablet to control their blood sugar level. | Drug: Vildagliptin 50 mg Oral Tablet<br>* Patients who the endocrinologist prescribed them Vildagliptin 50 mg Oral Tablet plus their Metformin 1000 mg Oral Tablet to control their blood sugar level.<br>* Other names: Galvus 50 mg;Drug: Metformin 1000 mg Oral Tablet<br>* Patients with Coronary artery diseases.and uncontrolled Diabetes Mellitus type 2 who's taking Metformin 1000 mg Oral Tablet only will be enrolled from endocrinology clinic.<br>* Other names: Glucophage 1000 mg;|
| Experimental: glimepiride / metformin.<br>Group II (n=40) are patients who are taking Glimepiride 4 mg oral tablet plus their metformin1000 mg oral tablet to control their blood sugar level. | Drug: Metformin 1000 mg Oral Tablet<br>* Patients with Coronary artery diseases.and uncontrolled Diabetes Mellitus type 2 who's taking Metformin 1000 mg Oral Tablet only will be enrolled from endocrinology clinic.<br>* Other names: Glucophage 1000 mg;Drug: Glimepiride upto 4 mg Oral Tablet<br>* Patients who the endocrinologist prescribed them Glimepiride 4 mg oral tablet plus their Metformin 1000 mg Oral Tablet<br>* Other names: Amaryl 4 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in markers of athero-thrombosis and inflammation ( interleukin (IL)-1 beta). | A-Change in interleukin (IL)-1 beta (IL-1ß) level will be determined by Enzyme-linked immunosorbent assay (ELISA). (unit: Picogram/milliliter pg/ml). | Baseline and 3 months | 
| Change in High sensitivity C-reactive protein (hsCRP) level. | A- High sensitivity C-reactive protein (hsCRP) level will be determined by nephelometric procedure.(unit: mg/L) | Baseline and 3 months | 
| Change in Adiponectin level. | A- Adiponectin level will be determined by Enzyme-linked immunosorbent assay (ELISA)..(unit: mg/L) | Baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Lipid profile | A-Change inTriglycerides (TGs). (Unit : milligrams per deciliter (mg/dL)) B-Change in total cholesterol (TCH). (Unit : milligrams per deciliter (mg/dL)) C-Change in high-density lipoprotein (HDL-C). (Unit : milligrams per deciliter (mg/dL)) D-change in Low density lipoprotein cholesterol (LDL-C). (Unit : milligrams per deciliter (mg/dL)) | Baseline and 3 months | 
| Percent Change in ( Low-density lipoprotein (LDL) cholesterol / High-density lipoprotein (HDL) cholesterol ) for each patient before and after 3 months combination treatment for each group . | Percent Change in (Low-density lipoprotein (LDL) cholesterol/High-density lipoprotein (HDL) cholesterol) =(combination treatment value - baseline value) / baseline value*100 | Baseline and 3 months | 
| Change in Hemoglobin A1c (HbA1c). | A-Change in Hemoglobin A1c (HbA1c) by ion exchange method.(Unit : percent ) | Baseline and 3 months | 
| Percent Change in (total cholesterol / High-density lipoprotein (HDL) cholesterol) for each patient before and after 3 months combination treatment for each group . | Percent Change in (total cholesterol / High-density lipoprotein (HDL) cholesterol) =(combination treatment value - baseline value) / baseline value*100 | Baseline and 3 months |