Effect of Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number Type 2 Diabetes
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Vildagliptin; Glibenclamide; Metformin
Intervention description: 100 mg daily; 2.5 mg (total daily), progressively increased up to a maximum dose of 5 mg x 2/ day.; concomitant therapy with metformin is present in each arm (MAX dose: 2500 mg/die)
Intervention MeSH terms: Metformin; Vildagliptin; Glyburide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 64.0
Sex: All
Minimum age: 35 Years
Healthy volunteers: No
Keywords: EPC; diabetes; DPP IV inhibitors

Summary:

      The purpose of this study is to evaluate the effect of Dipeptidyl peptidase (DPP) -IV
      inhibitor Vildagliptin vs. Glibenclamide on circulating endothelial progenitor cells (EPCs)
      number in type 2 diabetes patients in metformin failure. Subjects will be followed for 12
      months after randomization.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age equal or above 35 years;

          -  Diagnosis of type 2 diabetes mellitus as defined by the American Diabetes Association
             , with at least one year of disease duration at the time of the screening visit;

          -  Blood glucose lowering treatment with Metformin alone (monotherapy) at a stable dose
             of at least 1.5 g/day (or maximum tolerated dose) in the 3 months prior to the
             screening visit;

          -  Insufficient metabolic control as defined by recent (last six months) HbA1c ≥ 7% in
             any peripheral laboratory and confirmed at the time of the screening;

          -  Absence of a recent clinically-relevant progression of micro- and macro-vascular
             complications (see exclusion criteria);

          -  Written informed consent to participate to the study.

        Exclusion criteria:

          -  Age below 35 years

          -  Type 1 diabetes or other causes of diabetes (pancreatectomy, gestational diabetes,
             etc.)

          -  HbA1c < 7% or ≥ 9% at the screening visit

          -  Treatment with any blood glucose lowering treatment other than Metformin in the six
             months before screening visit

          -  BMI < 20 or ≥ 40 kg/m2, or current/ past history of clinically-relevant eating
             disorders (including -but no limited to- nervous anorexia, bulimia, binge-eating
             disorders, etc.)

          -  Significant progression of diabetic macro-angiopathy or cardiovascular disease in the
             six months prior to study visit

          -  Significant progression of diabetic micro-angiopathy in the six months prior to study
             visit

          -  Organ failure or other severe diseases limiting life expectancy;

          -  Beginning, in the three months before screening visit, of any kind of drug which can
             modify glycemic levels (beta-blockers, diuretics…), or acute disease (acute infection,
             urinary tract infection…) in three months before screening visit

          -  History of inflammatory/infective/autoimmune chronic disease

          -  History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, gastric
             surgery, inflammatory bowel disease;

          -  Any clinically significant abnormality identified on physical examination, laboratory
             tests, ECG or vital signs at screening that in the judgment of the investigator would
             preclude safe completion of the study;

          -  Uncontrolled or inadequately controlled hypertension at screening (Systolic Blood
             Pressure (SBP)>190 or Diastolic Blood Pressure (DBP) >100 mmHg)

          -  Ongoing pregnancy or absence of effective contraception in women with childbearing
             potential

          -  Contraindications to the maintenance of the background therapy (Metformin), including
             -but not limited to- chronic kidney failure or plasma creatinine concentrations > 1.5
             mg/dL, severe respiratory failure, etc.;

          -  Contraindications to the use of a Sulfonylurea;

          -  Contraindications to the use of a DPP-IV Inhibitor;

          -  Laboratory findings, or other disease conditions, at the screening visit that might
             interfere with study measurements:

               1. Hemoglobinopathy known to affect HbA1c assays;

               2. Known chronic liver diseases, including HBV (hepatitis B virus) and HCV
                  (hepatitis C virus) infection;

               3. Liver makers (aspartate transaminase (AST), alanine aminotransferase (ALT),
                  alkaline phosphatase (ALP), Gamma-glutamyltransferase (GGT) , bilirubin) above 2
                  times the upper normal limit;

               4. Amylase and/or lipase above 2 times the upper normal limit;

          -  Chronic use of systemic and/or inhaled corticosteroids (only topical corticosteroids
             are allowed);

          -  History of low compliance, clinically-relevant psychiatric disorders or any current/
             historical finding suggesting the patient as inappropriate to follow the study
             procedures.