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NCT Number: NCT03010683

Effects of Agonists of Glucagon Like Peptide - 1 Receptors (GLP-1R) on Arterial Stiffness, Endothelial Glycocalyx and Coronary Flow Reserve in Patients With Coronary Artery Disease and Patients With Diabetes Mellitus

Arterial stiffness is associated with increased risk for cardiovascular disease. Moreover, the integrity of endothelial glycocalyx plays a vital role in vascular permeability, inflammation and elasticity. Agonists of Glucagon like peptide - 1 receptors (GLP-1R) used in the treatment of type 2 diabetes mellitus (T2DM). This category includes exenatide and liraglutide. These drugs lower glucose levels by inhibiting the secretion of glucagon, promoting the release of insulin in response to hyperglycemia, slowing gastric emptying, and augmenting satiety. Clinical studies have shown that GLP-1R agonists have beneficial effects on cardiovascular function in both diabetic patients and healthy subjects. The purpose of this study is to investigate in patients with T2DM without coronary artery disease (CAD), patients with T2DM and CAD and obese patients with abnormal oral glucose tolerance test (OGTT), changes in arterial stiffness, endothelial glycocalyx thickness and coronary reserve flow (CFR) after treatment with metformin or agonist GLP-1R.

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Key information

Conditions

Type 2 Diabetes Mellitus Arterial Occlusive Diseases Arteriosclerosis Cardiovascular Diseases Coronary Artery Disease Coronary Disease Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Heart Diseases Metabolic Diseases Myocardial Ischemia Nutritional and Metabolic Diseases Vascular Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

''Attikon'' University General Hospital

Athens, Attica, 12462, Greece

About this study

The investigators will study three groups matched for age and sex: 30 patients with type 2 diabetes mellitus (T2DM) without coronary artery disease (CAD), 30 patients with T2DM and CAD and 30 obese patients (BMI >30 Kg/m²) with abnormal oral glucose tolerance test (OGTT). It will be a randomized study with metformin or GLP-1R agonist treatment for 1 year. All subjects will receive for 1 year: (a) GLP-1R agonist or (b) metformin. At 0, 3, 6 and 12 months, where 0 is the starting point of treatment, blood samples will be collected.

At 0, 3, 6 and 12 months the investigators will measure:

  • Carotid-femoral pulse wave velocity (PWV, m/sec) using tonometry by Complior (SP ALAM) and augmentation index (AI, %) by the method of arteriography (Arteriograph, TensioMed)
  • Perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels (ranged from 5-25 micrometers) using Sideview Darkfield imaging (Microscan, Glycocheck). Increased PBR is considered an accurate non invasive index of reduced endothelial glucocalyx thickness.
  • Coronary flow reserve (CFR) in the left anterior descending artery after infusion of adenosine using Doppler echocardiography.
  • Determination of the following parameters in blood: glucose, insulin, free fatty acids, triglycerides, glycerol, C reactive protein (CRP), transforming growth factor-b (TGF-b), Lipoprotein-Associated Phospholipase A2 (LP-LPA2), tumor necrosis factor-a (TNF-a), interleukins 6 and 10 (IL6 and IL10), propeptide of type I procollagen (PIP), propeptide of procollagen type III (PIIINP), matrix metallopeptidases 9 and 2 (MMP), macrophage-colony stimulating factor (MCSF), growth differentiation factor-15 (GDF-15), N-terminal pro b-type natriuretic peptide (NT-proBNP) and galectin-3.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients with type 2 diabetes mellitus (T2DM) without coronary artery disease (CAD)
  • Patients with T2DM and CAD.
  • Obese patients (BMI >30 Kg/m²) with abnormal oral glucose tolerance test (OGTT)

Exclusion criteria

  • valvular heart disease
  • congestive heart failure
  • peripheral vascular disease
  • liver or kidney failure
  • history of alcohol or drug abuse

Treatment and study plan

liraglutide

Drug

Stimulation of Glucagon like peptide-1 receptor by liraglutide (Victoza) 1.8mg once daily as a subcutaneous injection

Other names: Victoza (liraglutide)

metformin

Drug

Antidiabetic drug-biguanide class (Glucophage) 1000mg twice daily per os

Other names: Glucophage (Metformin)

Primary outcomes

  1. Differences in Pulse Wave Velocity at Baseline and 3, 6 and 12 Months After Treatment With Metformin or Agonist GLP-1R.

    Time frame: Baseline, 3 months, 6 months and 12 months

    Differences in carotid-femoral pulse wave velocity (PWV, m/sec) using tonometry at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R.

  2. Differences in Augmentation Index at Baseline and 3, 6 and 12 Months After Treatment With Metformin or Agonist GLP-1R.

    Time frame: Baseline, 3 months, 6 months, and 12 months.

    Differences in augmentation index (AI, %) using oscillometry at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R.

  3. Differences in Coronary Flow Reserve at Baseline and 3, 6 and 12 Months After Treatment With Metformin or Agonist GLP-1R.

    Time frame: Baseline, 3 months, 6 months, and 12 months.

    Differences in coronary flow reserve (CFR) using Doppler echocardiography at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R.

  4. Differences in Endothelial Glycocalyx Thickness at Baseline and 3, 6 and 12 Months After Treatment With Metformin or Agonist GLP-1R.

    Time frame: Baseline, 3 months, 6 months, and 12 months.

    Differences in endothelial glycocalyx thickness as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R. High PBR values represent reduced glycocalyx thickness.

Secondary outcomes

  1. Endothelial Glycocalyx and Pulse Wave Velocity.

    Time frame: Baseline, 3 months, 6 months, and 12 months.

    Association of endothelial glycocalyx thickness as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels with pulse wave velocity (PWV, m/sec) at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R.

  2. Endothelial Glycocalyx and Coronary Flow Reserve.

    Time frame: Baseline, 3 months, 6 months, and 12 months.

    Association of endothelial glycocalyx thickness as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels with coronary flow reserve (CFR) using Doppler echocardiography at baseline and 3, 6 and 12 months after treatment with metformin or agonist GLP-1R.

Sponsors and collaborators

Lead sponsor

University of Athens

Other

Registry information

Important dates

Study start
2015
Primary completion
2017
Study completion
2017
First posted
Jan 5, 2017
Registry last updated
Mar 5, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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