We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu

Effects of Antidiabetic Medications on the Postprandial State in Prediabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02104739
Recruitment Status : Completed
First Posted : April 4, 2014
Last Update Posted : May 8, 2017
Information provided by (Responsible Party):

Study Description
Brief 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.

Condition or disease Intervention/treatment Phase
Prediabetes Obesity Drug: Exenatide Drug: Saxagliptin Drug: Exenatide ER Other: Placebo Phase 4

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). 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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Placebo pills and placebo injections provided
Primary Purpose: Treatment
Official Title: Comparative Effects of Antidiabetic Medications on Postprandial Hyperlipidemia, Free Fatty Acid Signaling, and Endothelial Dysfunction in Individuals With Prediabetes
Study Start Date : March 2014
Primary Completion Date : March 2017
Study Completion Date : March 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prediabetes
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Saxagliptin
Saxagliptin 5 mg orally
Drug: Saxagliptin
Single dose orally (5 mg)
Other Name: Onglyza
Experimental: Exenatide ER
Exenatide ER 2mg subcutaneously
Drug: Exenatide ER
Subcutaneous injection (2mg) weekly for 6 weeks
Other Name: Bydureon
Placebo Comparator: Placebo
Other: Placebo
Placebo tablets and Placebo (normal saline) injections
Experimental: Exenatide
Exenatide 10 mcg subcutaneously
Drug: Exenatide
Single subcutaneous injection (10 mcg)
Other Name: Byetta

Outcome Measures

Primary Outcome Measures :
  1. Monocyte NfkB [ Time Frame: 2 hours after ingestion of meal ]
    Monocyte NfkB

Secondary Outcome Measures :
  1. Triglycerides [ Time Frame: 6 hours after ingestion of meal ]

Other Outcome Measures:
  1. Forearm blood flow [ Time Frame: 6 hours after meal ]
    Forearm blood flow via strain gauge venous occlusion plethysmography

  2. Free Fatty Acids [ Time Frame: 6 hours after meal ]
    Free Fatty Acids

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   30 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. Men and women, ages 30 to 70 years of age inclusive
  2. 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%
  3. 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
  4. BMI between 30-35 kg/m2 (±1 kg/m2)
  5. Body weight has been stable (±4-5 pounds) over the prior three months.
  6. 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
  7. 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:

  1. History of Type 1 or Type 2 diabetes mellitus
  2. History of diabetic ketoacidosis or hyperosmolar nonketotic coma
  3. Pregnant or breastfeeding women
  4. Patients must not be receiving lipid-lowering medications other than statins within the last 3 months
  5. 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.
  6. Patients must not be on hormone replacement therapy.
  7. Patients with diabetic gastroparesis
  8. Patients with current tobacco use
  9. Patients with active malignancy
  10. Patients with history of urinary bladder cancer
  11. Patients with dietary restrictions precluding a high-fat meal
  12. 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
  13. Subjects with a history of any serious hypersensitivity reaction to the study medications
  14. Prisoners or subjects who are involuntarily incarcerated
  15. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
  16. Subjects with known allergic reactions to the study medications or test meal
  17. Subjects unwilling or unable to provide informed consent
  18. Subjects determined by the investigator(s) to not be appropriate candidates for the study
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02104739

United States, Texas
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
The Center for Clinical and Translational Sciences (CCTS) Clinical Research Unit at The University of Texas Health Science Center at Houston
Principal Investigator: Absalaon D Gutierrez, MD University of Texas Health Science Center at Houston, Dept. of Medicine
More Information

Responsible Party: Absalon D Gutierrez, Assistant Professor of Medicine, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT02104739     History of Changes
Other Study ID Numbers: HSC-MS-13-0791
First Posted: April 4, 2014    Key Record Dates
Last Update Posted: May 8, 2017
Last Verified: May 2017

Keywords provided by Absalon D Gutierrez, The University of Texas Health Science Center, Houston:
diabetes mellitus type 2
exenatide ER

Additional relevant MeSH terms:
Prediabetic State
Glucose Intolerance
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action