Effects of Vildagliptin/Metformin Combination on Markers of Atherosclerosis, Thrombosis, and Inflammation in Diabetics With Coronary Artery Disease

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that combined vildagliptin-metformin therapy is associated with clinically significant reductions in biological markers of inflammation, pro-thrombogenicity, and atherosclerosis as compared to metformin mono-therapy in a population of diabetic patients with coronary artery disease who undergo cardiac rehabilitation. The pre-specified established biological markers of inflammation, pro-thrombogenicity, and atherosclerosis will include: interleukin-6 (IL-6 - primary biological marker), hs-CRP, platelet reactivity testing, MMP-9, Interleukin 1 beta (IL-1 beta) and adiponectin levels.

Detailed Description
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The study is designed as a single-center, randomized, non-blinded, clinical trial to provide evidence on the effects of vildagliptin on key biomarkers of atherothrombosis and inflammation. We plan to prospectively enroll 60 patients with proven coronary artery disease and randomize them in a 2:1 ratio to either vildagliptin-metformin therapy (n=40) or metformin therapy (n=20).

Official Title
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Effects of Vildagliptin/Metformin Combination on Markers of Atherosclerosis, Thrombosis, and Inflammation in Diabetic Patients With Coronary Artery Disease

Conditions
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Type 2 Diabetes Mellitus, Ischemic Heart Disease

Intervention / Treatment
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* Drug: Metformin plus vildagliptin
* Drug: Metformin only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 Diabetes Mellitus on oral mono-therapy or diet only treatment Stable documented ischemic Heart disease (>30 days post AMI, CABG or PCI) Sub-optimal Hb A1c as defined ≥6.5% Age > 21 Life expectancy >1 year Exclusion Criteria: Significant renal impairment (creatinine ≥1.4 mg\dL females or ≥1.5 mg\dL males) Planned coronary intervention or planed surgical intervention (PCI or CABG) Planned surgical intervention Recent (<30 day) acute coronary syndrome (ACS) Hypersensitivity to either of the study drug components History of lactic acidosis Type I diabetes Current Hb A1c >9% Current Insulin treatment Active treatment with GLP-1 or DPP4i medication Hepatic impairment or ALT\AST elevations beyond X2 upper normal limit or known hepatic failure Inability to comply with study protocol Active malignancy other than basal cell carcinoma (BCC) Clinically advanced congestive heart failure - NYHA III-IV Severe left ventricular dysfunction (LVEF<30%) with NYHA II or any NYHA class with documented recent heart failure decompensation (<3 months) Severe stable cardiac angina CCS III - IV or Unstable angina Chronic inflammation (i.e. IBD, Lupus, inflammatory arthritis, rheumatoid arthritis) or chronic infection (i.e. chronic diabetic foot infection) Pregnancy, lactation or child-bearing potential

Ages Eligible for Study
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Minimum Age: 21 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vildagliptin+metformin<br>Oral Vildagliptin+metformin combination | Drug: Metformin plus vildagliptin<br>* Oral Metformin 850mg and vildagliptin 50mg, qd initially, up-titrated to BID if clinically necessary<br>* Other names: Eucreas;|
| Active Comparator: Metformin only<br>Oral metformin only | Drug: Metformin only<br>* Oral Metformin 850mg QD, up-titrated to 850mg TID is clinically indicated<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in serum levels of Interleukin 6 (IL-6) |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in other markers of athero-thrombosis and inflammation: | I. Improvement in other markers of athero-thrombosis and inflammation: High sensitivity C-reactive protein (hs-CRP), Platelet reactivity Adiponectin levels IL-1 beta Matrix metallo-peptidase 9 (MMP-9) Additional exploratory markers including: IL-1 alpha ,, IL-17, TNF-alpha, MCP-1 | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes mellitus, vildagliptin, metformin, atherosclerosis, inflammation, interleukin-6, TNF, atherothrombosis, adiponectin, MMP-9, hs-CRP