Effects of Exercise and GLP-1 Agonism on Muscle Microvascular Perfusion and Insulin Action in Adults With Metabolic Syndrome


The primary objective of this study is to examine whether exercise training alone, liraglutide treatment alone or exercise training plus liraglutide treatment increases cardiac and skeletal muscle microvascular blood volume, improves vascular function of the conduit vessels, and enhances insulin's metabolic action in humans with Metabolic Syndrome. Subjects will be randomized to one of the 4 groups: control, exercise training, liraglutide treatment, and exercise + liraglutide. They will be studied at the baseline and then after 24 weeks of intervention.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Factorial Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 1, 2025

Detailed Description

Our hypothesis is that sustained activation of the GLP-1 receptor with Liraglutide and exercise training each will enhance microvascular insulin responses and angiogenesis in both cardiac and skeletal muscle to increase muscle insulin delivery and action and the combination of both is more effective than either alone in adults with metabolic syndrome.


  • Drug: Liraglutide
    • 24 weeks of Liraglutide
  • Other: Exercise training
    • 24 weeks of Exercise training
  • Drug: Liraglutide + Exercise training
    • 24 weeks of Liraglutide + Exercise training

Arms, Groups and Cohorts

  • No Intervention: Control
    • 24 weeks of observation
  • Experimental: Exercise Alone
    • 24 weeks of treatment
  • Experimental: Liraglutide Alone
    • 24 weeks of treatment
  • Experimental: Exercise + Liraglutide
    • 24 weeks f treatment

Clinical Trial Outcome Measures

Primary Measures

  • Microvascular Blood Volume – change from baseline
    • Time Frame: 24 weeks
    • measured at baseline and 24 weeks

Secondary Measures

  • Augmentation Index – change from baseline
    • Time Frame: 24 weeks
    • measured at baseline and 24 weeks
  • Flow Mediated Dilation
    • Time Frame: 24 weeks
    • measured at baseline and 24 weeks
  • Pulse Wave Velocity
    • Time Frame: 24 weeks
    • measured at baseline and 24 weeks
  • Post Ischemic Flow Velocity – change from baseline
    • Time Frame: 24weeks
    • measured at baseline and 24 weeks
  • Insulin Sensitivity – change from baseline
    • Time Frame: 24 weeks
    • measured at baseline and 24 weeks

Participating in This Clinical Trial

Inclusion Criteria

  • Male or female ≥21 and ≤60 years old. – Body mass index >25 and ≤35 kg/m2 and is weight stable (<5 kg weight change in the past 6 months). BMI is limited to ≤35 kg/m2 for easier vascular access and cardiac imaging. – Meet 3 of 5 National Cholesterol Education Program Adult Treatment Panel III Metabolic Syndrome criteria: – Increased waist circumference (≥102 cm in men; ≥88 cm in women) – Elevated triglycerides (≥150 mg/dl) – Reduced HDL-cholesterol (<40mg/dl in men, <50 mg/dl in women) – High blood pressure (≥130 mmHg systolic or ≥85mmHg diastolic) – Elevated fasting glucose (≥100 mg/dl) – Subject may participate if on the following drugs, provided the drug doses have been stable for at least 3 months. – Ace inhibitor – ARB – HMG CoA reductase inhibitor – Beta blocker – Calcium channel blockers – Alpha-adrenergic antagonist – Statin Exclusion Criteria:

  • A diagnosis of any type of diabetes or history of diabetes medication use – Recently active (>20 min of moderate/high intensity exercise, 2 times/week) – Subjects who are smokers or who have quit smoking <5 years – Subjects with hypertriglyceridemia (>400 mg/dl) or hypercholesterolemia (>260 mg/dl) – Subjects with BP>160/90 – Subjects with a history of significant metabolic, cardiac, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or malignancy – Pregnant (as evidenced by positive pregnancy test) or nursing women – Subjects with contraindications to participation in an exercise training program – Allergic to perflutren – A prior use of Liraglutide

Gender Eligibility: All

Minimum Age: 21 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • University of Virginia
  • Collaborator
    • National Institutes of Health (NIH)
  • Provider of Information About this Clinical Study
    • Principal Investigator: Zhenqi Liu, Professor and Chief, Division of Endocrinology and Metabolism – University of Virginia
  • Overall Official(s)
    • Zhenqi Liu, MD, Principal Investigator, Division of Endocrinology and Metabolism, University of Virginia
  • Overall Contact(s)
    • Lee Hartline, MEd, 434-924-5247, lmh9d@virginia.edu


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