Effects of Antidiabetic Medications on the Postprandial State in Prediabetes
Condition: Prediabetes; Obesity
MeSH terms: Prediabetic State; Glucose Intolerance
Intervention: Exenatide; Saxagliptin; Exenatide extended-release (ER); Placebo
Intervention description: Single subcutaneous injection (10 mcg); Single dose orally (5 mg); Subcutaneous injection (2mg) weekly for 6 weeks; Placebo tablets and Placebo (normal saline) injections
Intervention MeSH terms: Exenatide; Saxagliptin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Placebo pills and placebo injections provided
Enrollment: 21.0
Sex: All
Minimum age: 30 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: prediabetes; diabetes mellitus type 2; exenatide; saxagliptin; exenatide ER

Summary:

      This project addresses cardiovascular disease risk in patients with prediabetes. Levels of
      lipids after eating a meal ("postprandial lipids") are strong independent predictors of
      cardiovascular risk. Newer anti-diabetic agents - exenatide and saxagliptin - impact lipid
      metabolism. These medications will be studied for their effect in reducing both postprandial
      lipid levels and arterial dysfunction.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of Prediabetes - defined as either impaired fasting glucose (fasting glucose
             of 100-125 mg/dL), impaired glucose tolerance (2-hour postprandial blood glucose of
             140-199 mg/dL after 75 gram oral glucose challenge), and/or a hemoglobin A1C ranging
             from 5.7% to 6.4%

          -  Subjects are allowed, but not required, to be on statins, ACE-inhibitors,
             beta-blockers, angiotensin-receptor blockers, thiazide diuretics, and/or loop
             diuretics at doses that have been stable for at least the last 3 months

          -  BMI between 30-35 kg/m2 (±1 kg/m2)

          -  Body weight has been stable (±4-5 pounds) over the prior three months.

          -  Women of childbearing age must agree to use an acceptable method of pregnancy
             prevention (barrier methods, abstinence, or surgical sterilization) for the duration
             of the study

          -  Patients must have the following laboratory values: Hematocrit ≥ 34 vol% S. creatinine
             < 1.5 mg/dl in men and 1.4 mg/dl in women AST (SGOT) < 2.5 times ULN, ALT (SGPT) < 2.5
             times ULN, alkaline phosphatase< 2.5 times ULN

        Exclusion Criteria:

          -  History of Type 1 or Type 2 diabetes mellitus

          -  History of diabetic ketoacidosis or hyperosmolar nonketotic coma

          -  Pregnant or breastfeeding women

          -  Patients must not be receiving lipid-lowering medications other than statins within
             the last 3 months

          -  Patient must not be receiving metformin, DPP-IV inhibitors, GLP-1 agonists,
             thiazolidinediones, insulin, sulfonylureas, acarbose, SGLT-2 inhibitors,
             corticosteroids, or immunosuppressive therapy within the last 3 months and cannot take
             them for the duration of the study. Patient must not be receiving NSAIDS or
             antioxidant vitamins within the last 1 week, and cannot take them for the duration of
             the study.

          -  Patients must not be on hormone replacement therapy.

          -  Patients with diabetic gastroparesis

          -  Patients with current tobacco use

          -  Patients with active malignancy

          -  Patients with history of urinary bladder cancer

          -  Patients with dietary restrictions precluding a high-fat meal

          -  Patients with a history of clinically significant heart disease (NYHA III or IV; more
             than non- specific ST-T wave changes on the EKG), peripheral vascular disease (history
             of claudication), or pulmonary disease (dyspnea on exertion of one flight or less;
             abnormal breath sounds on auscultation) will not be studied

          -  Subjects with a history of any serious hypersensitivity reaction to the study
             medications

          -  Prisoners or subjects who are involuntarily incarcerated

          -  Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (e.g., infectious disease) illness

          -  Subjects with known allergic reactions to the study medications or test meal

          -  Subjects unwilling or unable to provide informed consent

          -  Subjects determined by the investigator(s) to not be appropriate candidates for the
             study