Effect of Adding Vildagliptin on Beta Cell Function and Cardiovascular Risk Markers in Patients With Moderate Metabolic Control During Metformin Monotherapy

Study Overview
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Brief Summary
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The aim of this pilot-study is to investigate the effect of Vildagliptin in comparison to glimepiride on beta cell function and the cardiovascular risk profile in patients previously treated with Metformin monotherapy.

Official Title
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Effect of Adding Vildagliptin on Beta Cell Function and Cardiovascular Risk Markers in Patients With Moderate Metabolic Control During Metformin Monotherapy

Conditions
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Diabetes Mellitus Type II

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetes mellitus type 2 HbA1c > 6.5%* ≤ 9.5% * NOTE: Patients with cardiovascular preconditions (Coronary Heart Disease or Myocard Infarction) require an HbA1c > 7.0% ≤ 9.5% Treatment with Metformin at maximal or maximal tolerated dosage, stable for at least 3 months with indication for treatment with an additional medication as judged by the investigator Age 30 - 80 years Patient consents that his/her family physician will be informed of trial participation Exclusion Criteria: Pre-treatment with insulin, peroxisome proliferator activated receptor (PPAR) gamma agonists or other oral antidiabetic treatments (except Metformin) within the last three months History of type-1-diabetes Fasting blood glucose >240mg/dl Uncontrolled hypertension (systolic blood pressure >160 and/or diastolic blood pressure >90) Anamnestic history of acute infections Anamnestic history of epilepsy Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures History of severe or multiple allergies Hereditary galactose intolerance, lapp-lactase defect or glucose-galactose mal-absorption Treatment with any other investigational drug within 3 months before trial entry Pregnant or lactating women Sexually active woman of childbearing age not practicing a highly effective method of birth control as defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal intrauterine devices, sexual abstinence or vasectomized partner Progressive fatal disease History of drug or alcohol abuse in the past 2 years State after kidney transplantation Serum potassium > 5.5 mmol/L Acute myocardial infarction, open heart surgery or cerebral event (stroke/transient ischemic attack) within the previous 6 months Any elective surgery during study participation Have had more than one unexplained episode of severe hypoglycemia (defined as requiring assistance of another person due to disabling hypoglycemia) within 6 months prior to screening visit History of pancreatitis Anamnestic history of dehydration, diabetic precoma or diabetic ketoacidosis Acute or scheduled investigation with iodine containing radiopaque material Uncontrolled unstable angina pectoris Anamnestic history of pericarditis, myocarditis, endocarditis, hemodynamic relevant aortic stenosis, aortic aneurysm or heart insufficiency NYHA III or IV Anamnestic recent pulmonary embolism History of significant cardiovascular, respiratory, gastrointestinal, hepatic (ALAT and/or ASAT > 3 times the normal reference range), renal (GFR < 60 ml), neurological, psychiatric and/or hematological disease as judged by the investigator Lack of compliance or other similar reason that, according to investigator, precludes satisfactory participation in the study

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 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 plus Metformin<br>Metformin (1000 mg BID) + Vildagliptin 50 mg twice daily | Drug: Metformin<br>* Metformin 1000 mg BID<br>Drug: Vildagliptin<br>* Vildagliptin 50 mg twice daily<br>|
| Active Comparator: Glimepirid plus Metformin<br>Metformin (1000 mg BID) + Glimepiride (individual dosage) | Drug: Metformin<br>* Metformin 1000 mg BID<br>Drug: Glimepiride<br>* Glimepiride at individual dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial increase in intact proinsulin levels in patient treated with Vildagliptin and Metformin compared to intact proinsulin levels in patients treated with Glimepiride and Metformin (Area under the curve 0-300 min) |  | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting intact proinsulin levels |  | One year | 
| Max postprandial intact proinsulin levels |  | One year | 
| Retinal endothelial response to flicker light stimulation |  | One year | 
| Mean 24h systolic and diastolic blood pressure |  | One year | 
| Erythrocyte deformability |  | One year | 
| E-selectin |  | One year | 
| Change in body weight |  | One year | 
| hsCRP |  | One year | 
| HbA1c |  | One year | 
| Fasting blood glucose |  | One year | 
| Number of hypoglycemic events |  | One year | 
| Adverse events |  | One year | 
| Drug related adverse events |  | One year |