Type 2 Diabetes MellitusNCT03010683

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

A study testing Liraglutide and Metformin in people with Type 2 Diabetes Mellitus and Coronary Artery Disease, run by University of Athens at 1 site in Greece.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for: Type 2 Diabetes Mellitus, Coronary Artery Disease
What is being tested?: Liraglutide and Metformin
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 60 participants
Where: 1 siteGreece
Study dates: Nov 2015to Dec 2017
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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)

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Greece1 site

''Attikon'' University General Hospital
Athens, Attica, 12462

Other trials in Greece

About this study

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.

Read the detailed description

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.

Conditions: Type 2 Diabetes Mellitus, Coronary Artery Disease
Being tested: Liraglutide, Metformin
Keywords: Arterial stiffness, Endothelial glycocalyx, Coronary flow reserve
Medical subject headings: Diabetes Mellitus, Type 2, Coronary Artery Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LiraglutideDrug
Also called Victoza (liraglutide)
Stimulation of Glucagon like peptide-1 receptor by liraglutide (Victoza) 1.8mg once daily as a subcutaneous injection
MetforminDrug
Also called Glucophage (Metformin)
Antidiabetic drug-biguanide class (Glucophage) 1000mg twice daily per os

Study groups in NCT03010683
Study group	Role	What they receive
liraglutide	Active comparator	Not described Receives: Drug: Liraglutide
Metformin	Active comparator	Not described Receives: Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (2)

Endothelial Glycocalyx and Pulse Wave Velocity.
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.
Measured: Baseline, 3 months, 6 months, and 12 months.
Endothelial Glycocalyx and Coronary Flow Reserve.
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.
Measured: Baseline, 3 months, 6 months, and 12 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2015Dec 2017

First posted5 Jan 2017 (estimated)
Study startNov 2015
Primary completionJun 2017
Study completionDec 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Investigator
Enrolment: 60 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03010683
Sponsor's protocol ID: GLP1-DM-ATTIKON
Status last verified: Mar 2021
First submitted: 22 Dec 2016
Last updated: 5 Mar 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

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.
PubMed 32501595
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.
PubMed 29310645

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT03010683
Acronym / sponsor ID: GLP1-DM-ATTIKON
Conditions: Type 2 Diabetes Mellitus, Coronary Artery Disease
Keywords: Arterial stiffness, Endothelial glycocalyx, Coronary flow reserve
Study type: Interventional
Recruitment status: Completed
Enrolment: 60 participants (actual)
Lead sponsor: University of AthensUniversity, hospital or other
Study start: Nov 2015
Primary completion: Jun 2017 (actual)
Study completion: Dec 2017 (actual)
First posted: 5 Jan 2017 (estimated)
Results: Posted 5 Mar 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (investigator)
Number of arms: 2

Arm	Type	Receives
liraglutide	Active comparator	Drug: Liraglutide
Metformin	Active comparator	Drug: Metformin

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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)

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LiraglutideAlso: Victoza (liraglutide)Stimulation of Glucagon like peptide-1 receptor by liraglutide (Victoza) 1.8mg once daily as a subcutaneous injection	Drug	liraglutide
MetforminAlso: Glucophage (Metformin)Antidiabetic drug-biguanide class (Glucophage) 1000mg twice daily per os	Drug	Metformin

Primary outcome

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.
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.
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.
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.

2 secondary outcomes

Endothelial Glycocalyx and Pulse Wave Velocity.
Time frame: Baseline, 3 months, 6 months, and 12 months.
Endothelial Glycocalyx and Coronary Flow Reserve.
Time frame: Baseline, 3 months, 6 months, and 12 months.

Results and safety

Results posted to the registry on 5 Mar 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Liraglutide	30	30
Metformin	30	30

Primary outcome: 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. Mean (Standard Deviation). Unit: m/s

Measure	Liraglutide n = 30	Metformin n = 30
Baseline	11.8 (2.5)	11.2 (3)
3 months	11.6 (2.8)	11.5 (2.7)
6 months	10.3 (3.3)	11 (3)
12 months	10.5 (1.9)	10.8 (2)

Primary outcome: 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.. Mean (Inter-Quartile Range). Unit: percentage of the central pulse pressure

Measure	Liraglutide n = 30	Metformin n = 30
Baseline	18 (-1 to 31)	14 (-9 to 24)
3 months	15.8 (-2 to 29)	13.6 (-6 to 25)
6 months	13 (-2 to 31)	15 (-8 to 24)
12 months	13.9 (-1 to 32)	15.3 (-6 to 24)

Primary outcome: 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.

Population analysed: The investigators did not measure coronary flow reserve (CFR).

Primary outcome: 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.. Mean (Standard Deviation). Unit: micrometers

Measure	Liraglutide n = 30	Metformin n = 30
Baseline	2.1 (0.29)	2.13 (0.3)
3 months	2.07 (0.3)	2.15 (0.3)
6 months	2.5 (0.2)	2.13 (0.3)
12 months	2.04 (0.2)	2.10 (0.3)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 12 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Liraglutide	0 of 30 (0%)	0 of 30 (0%)	0 of 30
Metformin	0 of 30 (0%)	0 of 30 (0%)	0 of 30

Limitations and caveats (from the sponsor): Οur study has a modest number of subjects. Additional large scale studies are needed to expand our results.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32501595Gnesin 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.
Derived from this study: PubMed 29310645Lambadiari 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ignatios Ikonomidis, MD principal investigator

2nd Cardiology Department, University of Athens, Greece

George Pavlidis, MD principal investigator

2nd Cardiology Department, University of Athens, Greece

Vaia Lambadiari, MD principal investigator

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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Liraglutide and Metformin in people with Type 2 Diabetes Mellitus and Coronary Artery Disease, run by University of Athens at 1 site in Greece.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03010683, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2021.