The Cardiovascular Effect of GLP-1 Agonist, SGLT2 Inhibitor and Their Combination

NCT03878706 | Recruiting DMC

• 1 other identifier: 2790/03-11-2017
• Study Type: observational
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

A. Four groups of patients with type 2 diabetes mellitus with high or very high cardiovascular risk or heart failure with preserved ejection fraction (HFpEF) will be studied before and at 6 and 12 months of treatment:

• 60 patients treated with a combination of GLP1 analogue and SGLT2 inhibitor ± metformin
• 60 patients treated with GLP-1 agonist as a second step after metformin
• 60 patients treated with SGLT2 inhibitor as a second step after metformin
• 60 patients treated with a combination of insulin and other antidiabetic agents (metformin - DPP4 inhibitors) Individuals will be equal distributed as far as age, gender and body mass index concerned. In addition, patients suffered from kidney disease and retinopathy are excluded.

Conditions

Diabetes Mellitus, Type 2

Keywords

Endothelial glycocalyx integrity; Oxidative stress biomarkers; Arterial stiffness; GLS; NT-proBNP; GDF-15; MOTS-c

Outcome Measures

Primary Outcomes (1)

• Comparison of Global Longitudinal Strain (GLS) difference among treatment groups.

  Comparison of Global Longitudinal Strain (GLS) difference among treatment groups, measured by echocardiographic study

  12 months

Secondary Outcomes (15)

• Comparison of arterial stiffness markers difference among treatment groups.

  12 months

• Comparison of wave reflection markers difference among treatment groups

  12 months

• Comparison of central aortic blood pressure differences among treatment groups

  12 months

• Comparison of endothelial glycocalyx thickness difference among treatment groups

  12 months

• Comparison of oxidative stress and endothelial function biomarkers differences among treatment groups

  12 months

Study Arms (4)

GLP1 and SGLT2i group

60 patients treated with a combination of liraglutide and empagliflozin. All subjects will undergo an echocardiographic study to estimate GLS, left ventricular twisting-untwisting using speckle tracking imaging and carotid intima-media thickness. PWV, AIx, SBPao and PPao with Arteriograph, Mobilograph and Complior, and perfused boundary region (PBR) of sublingual vessels using Sideview Darkfield Imaging (Microscan, Glycockeck). PBR consists the cell-free space which is formed from the separation of red blood cells from plasma at the surface of the endothelial glycocalyx. Oxidative stress markers, vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, thrombomodulin, nitrites and nitrates, N-terminal pro B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, mitochondrial-derived peptide-c (MOTS-c), blood glucose, glycosylated hemoglobin (HbA1c) and lipid profile will be measured before and at 6 and 12 months of treatment.

GLP1 group

60 patients treated with liraglutide. All subjects will undergo an echocardiographic study in order to estimate GLS, left ventricular twisting-untwisting using speckle tracking imaging and carotid intima-media thickness. PWV, AIx, SBPao and PPao with Arteriograph, Mobilograph and Complior, and perfused boundary region (PBR) of sublingual vessels using Sideview Darkfield Imaging (Microscan, Glycockeck). PBR consists the cell-free space which is formed from the separation of red blood cells from plasma at the surface of the endothelial glycocalyx. Oxidative stress markers, vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, thrombomodulin, nitrites and nitrates, N-terminal pro B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, mitochondrial-derived peptide-c (MOTS-c), blood glucose, glycosylated hemoglobin (HbA1c) and a full lipidemic profile will be measured before and at 6 and 12 months of treatment.

SGLT2i group

60 patients treated with empagliflozin. All subjects will undergo an echocardiographic study in order to estimate GLS, left ventricular twisting-untwisting using speckle tracking imaging and carotid intima-media thickness. PWV, AIx, SBPao and PPao with Arteriograph, Mobilograph and Complior, and perfused boundary region (PBR) of sublingual vessels using Sideview Darkfield Imaging (Microscan, Glucockeck). PBR consists the cell-free space which is formed from the separation of red blood cells from plasma at the surface of the endothelial glycocalyx. Oxidative stress markers, vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, thrombomodulin, nitrites and nitrates, N-terminal pro B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, mitochondrial-derived peptide-c (MOTS-c), blood glucose, glycosylated hemoglobin (HbA1c) and a full lipidemic profile will be measured before and at 6 and 12 months of treatment.

Control group

60 patients treated with insulin and metformin.All subjects will undergo an echocardiographic study in order to estimate GLS, left ventricular twisting-untwisting using speckle tracking imaging and carotid intima-media thickness. PWV, AIx, SBPao and PPao with Arteriograph, Mobilograph and Complior, and perfused boundary region (PBR) of subglottic vessels using Sideview Darkfield Imaging (Microscan, Glucockeck). PBR consists the cell-free space which is formed from the separation of red blood cells from plasma at the surface of the endothelial glycocalyx. Oxidative stress markers, vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, thrombomodulin, nitrites and nitrates, N-terminal pro B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, mitochondrial-derived peptide-c (MOTS-c), blood glucose, glycosylated hemoglobin (HbA1c) and a full lipidemic profile will be measured before and at 6 and 12 months of treatment.

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

240 individuals (60 subjects in each group)

You may qualify if:

• Subject has type 2 diabetes mellitus
• Subject has high or very high cardiovascular risk
• Subject has heart failure with preserved ejection fraction

You may not qualify if:

• Subject has type 1 diabetes mellitus
• Subject has kidney disease
• Subject has retinopathy

Sponsors & Collaborators

• University of Athens: lead

Study Sites (1)

"Attikon" University General Hospital

Athens, Attica, 12462, Greece

RECRUITING

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Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood sample obtained from the subjects for oxidative stress markers (malondialdehyde and protein carbonyls), vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, thrombomodulin, nitrites and nitrates, N-terminal pro B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15 and mitochondrial-derived peptide-c (MOTS-c) measuring.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Ignatios Ikonomidis, Prof

  2nd Department of Cardiology, National and Kapodistrian University of Athens

  PRINCIPAL INVESTIGATOR

• Aimilianos N. Kalogeris, MD

  2nd Department of Cardiology, University of Athens

  PRINCIPAL INVESTIGATOR

• John A. Thymis, MD

  2nd Department of Cardiology,University of Athens

  PRINCIPAL INVESTIGATOR

• Vaia Lambadiari, Prof.

  National and Kapodistrian University of Athens

  PRINCIPAL INVESTIGATOR

• Georgios Dimitriadis, Prof.

  National and Kapodistrian University of Athens

  STUDY CHAIR

• Efstathios Iliodromitis, Prof.

  National and Kapodistrian University of Athens

  STUDY CHAIR

Central Study Contacts

Ignatios Ikonomidis, Prof.

CONTACT

00306944805732; ignoik@gmail.com

Aimilianos N. Kalogeris, MD

CONTACT

00306949630300; kalogeris.cardio@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Cardiology

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: March 18, 2019
• Study Start: November 3, 2017
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

GR (1)