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

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

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.

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).

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