Effects of Sitagliptin on Endothelial Function in Type 2 Diabetes on Background Metformin Therapy
Condition: Diabetes; Atherosclerosis
MeSH terms: Atherosclerosis; Diabetes Mellitus
Intervention: sitagliptin; Placebo
Intervention description: 100 mg pill, administered once/day orally; Matching placebo in appearance given once/day orally
Intervention MeSH terms: Sitagliptin Phosphate
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 38.0
Sex: All
Minimum age: 21 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: dipeptidyl peptidase-4 inhibitor; endothelium, vascular; diabetes type 2; nitric oxide; inflammation

Summary:

      The study is being performed to determine whether sitagliptin, a dipeptidyl peptidase-4
      inhibitor, both acutely and chronically improves blood vessel function. Patients with type 2
      diabetes who are on metformin will be enrolled in this study for up to 22 weeks in this
      double blinded cross over study where they will receive a sitagliptin pill once a day for 8
      weeks and during a separate 8 weeks receive a matching placebo pill. The treatment periods
      are divided by a 4 week period. Blood vessel function will be measured by ultrasound before
      and after a single dose of sitagliptin and placebo, as well as after 8 weeks of treatment
      with each. Blood will also be taken to measure blood markers of inflammation at each time the
      ultrasounds are performed.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult age 21-70 years of age.

          2. Diagnosis of type 2 diabetes by a physician as defined by the American Diabetes
             Association standard criteria: 1) Fasting Plasma glucose at or above 126 mg/dL 2) a
             two-hour value in an oral glucose tolerance test at or above 200 mg/dL, or 3) a random
             plasma glucose concentration 200 mg/dL in the presence of symptoms, or 4) glycosylated
             hemoglobin greater than or equal to 6.5%.

          3. On stable metformin therapy for at least 6 weeks prior to enrollment.

          4. Glycosylated Hemoglobin ≥6.2% and ≤ 9.5%.

        Exclusion Criteria:

          1. History of stroke, peripheral arterial disease, or coronary artery disease (as defined
             by the presence of at least one coronary stenosis ≥ 50% on angiography or by confirmed
             history of myocardial infarction by standard criteria.)

          2. Evidence of other evident major illness including chronic renal insufficiency
             (creatinine clearance less than 60 mL/min),chronic liver disease (AST or ALT greater
             than 2.5 x normal), or cancer currently undergoing systemic therapy or had systemic
             therapy for cancer within 1 year of enrollment.

          3. Pregnancy as determined by urinary beta-HCG test

          4. Illicit drug use (heroin, cocaine etc) in the past 1 year.

          5. Alcohol abuse, defined as the equivalent of 14 beers/week for a man or 7 beers/week
             for a woman

          6. History of allergy to DPP-4 inhibitors at the time of screening/enrollment

          7. Prior history of pancreatitis

          8. Patients currently on insulin or sulfonylurea therapy.

          9. Patients currently on digoxin.

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