This project tests the principle hypothesis that stable glucagon like peptide-1 (GLP-1) analogues have specific GLP1R-dependent beneficial effects on vascular endothelial function, fibrinolysis and inflammation in obesity that exceed the benefits of weight loss, and that genetic or other individual factors that modulate GLP1R sensitivity can modify the effect of these analogues on cardiovascular risk.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
329
subcutaneous liraglutide daily
oral sitagliptin daily
Reduced calorie intake to achieve weight loss.
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Change in Flow-mediated Dilation
Brachial artery diameter is measured under basal conditions and during reactive hyperemia (Flow Mediated Dilation as %)
Time frame: Baseline to 2 and 14 weeks
Urine Albumin-to-creatinine Ratio
Ratio of urine albumin to creatinine in a spot urine collected after overnight rest
Time frame: Baseline to 13 weeks
Change in Plasminogen Activator Inhibitor-1
Plasma plasminogen activator inhibitor-1 antigen
Time frame: Baseline to 2 and 14 weeks
Blood Pressure
The mean of three systolic blood pressure measurements one minute apart using a oscillometric recording device with patient in supine position
Time frame: Baseline, and after 2 weeks and 14 weeks of treatment
Heart Rate
The mean of three measurements with the patient in the supine position
Time frame: Baseline, and after 2 weeks and 14 weeks of treatment
Fasting Glucose
Blood glucose collected after overnight fast
Time frame: Baseline, and after 2 weeks and 14 weeks of treatment
Fasting Insulin
Plasma insulin collected after overnight fast
Time frame: Baseline, and after 2 weeks and 14 weeks of treatment
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Subjects in the liraglutide arm will receive a placebo for sitagliptin. Those in the sitagliptin arm will receive a placebo for liraglutide. All subjects will receive a placebo for Exendin 9-39.
All subjects will receive Exendin (9-39) or matching placebo in crossover fashion during study days on the first and third days of the second week after randomization and again on the 5th and 7th days of the 14th week of treatment.