Effects of Antidiabetic Medications on the Postprandial State in Prediabetes
Condition: Prediabetes; Obesity
MeSH terms: Prediabetic State; Glucose Intolerance
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      It is a paradox that medical efforts to control blood glucose in type 2 diabetes mellitus
      have not decreased the risk of cardiovascular disease. Postprandial lipid concentrations are
      a strong predictor of cardiovascular risk, independent of traditional cardiovascular risk
      factors. The new classes of antidiabetic medications - GLP-1 agonists and DPP-IV inhibitors -
      affect lipid as well as glucose metabolism. This study will investigate the efficacy of these
      medications in reducing postprandial hyperlipidemia, disrupting the concurrent
      proinflammatory free fatty acid signaling, and ameliorating endothelial dysfunction in
      individuals with prediabetes. This will consist of a single center, randomized, crossover,
      placebo-controlled double-blinded prospective trial involving three study arms representing
      the aforementioned medications: exenatide (GLP-1 agonist), saxagliptin (DPP-IV inhibitor),
      and placebo (control arm). Each subject will participate in each of the three arms, which are
      three separate, daylong outpatient studies. For each study arm, subjects will eat a
      standardized atherogenic high-fat test lunch. Venous blood draws and measurements of forearm
      blood flow will be done prior to the meal and periodically during a 6-hour period after the
      meal. Forearm blood flow measurements will assess for changes in endothelial function. The
      blood will be analyzed for multiple markers of hyperlipidemia and free fatty acid signaling.
      After completing the three randomized study visits, subjects are invited to participate in an
      optional, nonrandomized extension study. For the extension study, subjects will take
      exenatide ER (extended-release exenatide) weekly for total of six weeks. Then subjects return
      to eat a standardized atherogenic high-fat test lunch. Venous blood draws and measurements of
      forearm blood flow will be done prior to the meal and periodically during a 4-hour period
      after the meal, for the same analyses described before. The results will provide new insights
      into the anti-inflammatory effects of multiple antidiabetic medications via the mechanisms of
      postprandial hyperlipidemia, free fatty acid signaling, and endothelial function in
      prediabetic individuals.
    

Intervention name(s): Exenatide; Saxagliptin; Exenatide extended-release (ER); Placebo
Intervention type(s): Drug; Drug; Drug; Other
Intervention description(s): Single subcutaneous injection (10 mcg); Single dose orally (5 mg); Subcutaneous injection (2mg) weekly for 6 weeks; Placebo tablets and Placebo (normal saline) injections
Other intervention name(s): Byetta; Onglyza; Bydureon
Intervention MeSH terms: Exenatide; Saxagliptin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: prediabetes; diabetes mellitus type 2; exenatide; saxagliptin; exenatide ER