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

NCT03010683 | Completed Results DMC

• 1 other identifier: GLP1-DM-ATTIKON
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus; Coronary Artery Disease

Keywords

Arterial stiffness; Endothelial glycocalyx; Coronary flow reserve

Outcome Measures

Primary Outcomes (4)

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

  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.

  Baseline, 3 months, 6 months and 12 months

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

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

  Baseline, 3 months, 6 months, and 12 months.

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

  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.

  Baseline, 3 months, 6 months, and 12 months.

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

  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.

  Baseline, 3 months, 6 months, and 12 months.

Secondary Outcomes (2)

• Endothelial Glycocalyx and Pulse Wave Velocity.

  Baseline, 3 months, 6 months, and 12 months.

• Endothelial Glycocalyx and Coronary Flow Reserve.

  Baseline, 3 months, 6 months, and 12 months.

Study Arms (2)

liraglutide

ACTIVE COMPARATOR

Drug: Liraglutide

Metformin

ACTIVE COMPARATOR

Drug: Metformin

Interventions

Liraglutide DRUG

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

Also known as: Victoza (liraglutide)

liraglutide

Metformin DRUG

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

Also known as: Glucophage (Metformin)

Metformin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• University of Athens: lead

Study Sites (1)

''Attikon'' University General Hospital

Athens, Attica, 12462, Greece

Location

Related Publications (2)

• Gnesin F, Thuesen ACB, Kahler LKA, Madsbad S, Hemmingsen B. Metformin monotherapy for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Jun 5;6(6):CD012906. doi: 10.1002/14651858.CD012906.pub2.

  PMID: 32501595 DERIVED

• Lambadiari V, Pavlidis G, Kousathana F, Varoudi M, Vlastos D, Maratou E, Georgiou D, Andreadou I, Parissis J, Triantafyllidi H, Lekakis J, Iliodromitis E, Dimitriadis G, Ikonomidis I. Effects of 6-month treatment with the glucagon like peptide-1 analogue liraglutide on arterial stiffness, left ventricular myocardial deformation and oxidative stress in subjects with newly diagnosed type 2 diabetes. Cardiovasc Diabetol. 2018 Jan 8;17(1):8. doi: 10.1186/s12933-017-0646-z.

  PMID: 29310645 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Coronary Artery Disease

Interventions

Liraglutide; Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

Οur study has a modest number of subjects. Additional large scale studies are needed to expand our results.

Results Point of Contact

• Title: Dr Ignatios Ikonomidis
• Organization: 2nd Cardiology Department, National and Kapodistrian University of Athens, Attikon Hospital

ignoik@gmail.com

+30 6944805732

Study Officials

• Ignatios Ikonomidis, MD

  2nd Cardiology Department, University of Athens, Greece

  PRINCIPAL INVESTIGATOR

• George Pavlidis, MD

  2nd Cardiology Department, University of Athens, Greece

  PRINCIPAL INVESTIGATOR

• Vaia Lambadiari, MD

  2nd Department of Internal Medicine, University of Athens, Greece

  PRINCIPAL INVESTIGATOR

• Fotini Kousathana, MD

  2nd Department of Internal Medicine, University of Athens, Greece

  PRINCIPAL INVESTIGATOR

• George Dimitriadis, MD

  2nd Department of Internal Medicine, University of Athens, Greece

  PRINCIPAL INVESTIGATOR

• John Lekakis, MD

  2nd Cardiology Department, University of Athens, Greece

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor in Cardiology

Study Record Dates

• First Submitted: December 22, 2016
• First Posted: January 5, 2017
• Study Start: November 1, 2015
• Primary Completion: June 1, 2017
• Study Completion: December 1, 2017
• Last Updated: March 5, 2021
• Results First Posted: March 5, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)