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

NCT ID: NCT03878706

Last Updated: 2025-06-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Total Enrollment

240 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-11-03

Study Completion Date

2027-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Disordered glucose tolerance in patients with type 2 diabetes mellitus is multifactorial and includes dysfunction not only of β-cells of the pancreas, liver and muscles, but also of the adipose tissue, gastrointestinal tract, kidney, α-cells of the pancreas and the brain. Therefore, it is likely that the use of drugs that act on multiple aspects of the pathophysiology of diabetes will have beneficial effects on glycemic control and outcome of patients.In addition to the many possible causes of glucose deregulation, people with type 2 diabetes have comorbidities such as hypertension, hyperlipidemia and obesity resulting in increased cardiovascular risk. Optimal treatment of hyperglycaemia and cardiovascular risk factors is necessary to reduce adverse events. Although the initial approach is the modification of dietary factors (physical activity, diet, smoking cessation), the progressive nature of type 2 diabetes ultimately leads to the use of multiple therapies. Guidelines for the treatment of patients with type 2 diabetes with high HbA1c are initial double-combined therapy or triple combination if glycemic control is not achieved after 3 months. Although insulin is usually included in such combinations, additional treatment options are required for patients with high HbA1c who also need to lose weight and avoid hypoglycaemia. It is likely that the outcome of patients could be improved by using drugs targeting different aspects of the disease (glycemia, body weight, blood pressure, lipids).

Over the last decade, two classes of antidiabetic drugs have been added to weight loss, improved cardiovascular risk factors and a low risk of hypoglycemia: glucagon-like peptide-1 agonists (GLP-1, glucagon like peptide-1) and inhibitors of the sodium glucose subtype 2 (SGLT2, sodium-glucose co-transporters). Recent studies have shown that these two drugs have cardioprotective effects possibly through different mechanisms of action, while their complementary mechanical, pharmacological and clinical effects make their combination (in addition to metformin) potentially beneficial in type 2 diabetes patients. Specifically, SGLT2 inhibitors manifest their cardioprotective activity by improving hemodynamic parameters, while GLP-1 agonists through antiatherogen / anti-inflammatory mechanisms.

The increased arterial stiffness with the associated increase in the range of reflected pressure waves, determines not only the augmentation of systolic pressure but also the rate of increase which depends on age. Increased levels of pulse pressure (indirect atherosclerotic index) and pulse wave velocity (PWV), a reliable measure of arterial stiffness, predict future cardiovascular events. Endothelial dysfunction is associated with the presence of atherosclerosis and is also considered as an indicator of the early changes preceding it. The role of impaired endothelial function of large arteries seems to be significant in the pathogenesis of cardiovascular disease. Endothelial glycocalyx is a glycoprotein layer that covers the surface of endothelial cells and regulates arterial wall permeability and the interaction of endothelial cells with circulating blood cells. Inflammatory or atherogenic stimuli, such as hyperglycemia, lead to glucocalyx disorder and increased vascular sensitivity to further atherogenic stimuli. The two-dimensional speckle tracking ultrasound allows accurate estimation of left ventricular distortion, which is disordered in diabetics in relation to healthy subjects.

Hypothesis of the proposed study:

Endothelial function, arterial stiffness and left ventricular deformation are improved in patients with type 2 diabetes with high or very high cardiovascular risk or heart failure with preserved ejection fraction (HFpEF) treated with GLP-1 agonist and SGLT2 inhibitor compared to either one or both combination of insulin and other antidiabetic tablets.

Aim of the study:

The aim of this study is to investigate the effect of GLP-1 agonist, SGLT2 inhibitor and their combination on endothelial function, arterial stiffness, central hemodynamic characteristics and left ventricular deformation in patients with type 2 diabetes with high or very high cardiovascular risk or HFpEF and compared with the combination of insulin and other antidiabetic tablets.

Materials and methods :

A. Four groups of patients with type 2 diabetes mellitus with high or very high cardiovascular risk or 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.

B. All patients will be submitted to an echocardiographic study in order to estimate the total left ventricular and atrial myocardial global longitudinal strain (GLS) as well as the twisting-untwisting of the left ventricle using speckle tracking imaging. In addition, pulse wave velocity (PWV, measured in m/s), pulse wave augmentation index \[AIx %, which is calculated by the formula (P2-P1)/PP x 100, where P1 stands for peak systolic pressure, P2 stands for second peak systolic pressure due to wave reflection and PP stands for Pulse Pressure\], central systolic blood pressure (SBPao, measured in mm Hg) and central pulse pressure (PPao, measured in mm Hg) with Arteriograph, Mobilograph and Complior, and perfused boundary region (PBR) of sublingual vessels (5-25 μm in size) using a high-resolution camera with Sideview Darkfield Imaging technique (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. Increased PBR is considered to be an accurate indicator of the reduction of endothelial glycocalyx thickness due to plasma penetration into the glycocalyx.

Μalondialdehyde (MDA), protein carbonyls (PC) as 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 months and at 12 months of treatment.

The examination will be carried out at the Laboratory of Preventive Cardiology of the 2nd Department of Cardiology of the University of Athens at "Attikon" Hospital. Τhe investigators will also compare the participants with history of coronary artery disease with those without hisotry of coronary artery disease.

C. For the statistical analysis of the results, the significance of each intervention will be measured by t-test and the 4 groups will be compared by ANOVA (post-hoc comparisons with Bonferroni correction). Non-parametric tests will be used for non-Gaussian distributions. Forty individuals should be included in each group in order the results being statistically significant. In a previous study, myocardial global longitudinal strain of the left ventricle showed normal distribution with standard deviation 10. A true difference in mean left ventricular myocardial distortion between the intervention group (GLP-1 agonist compined with SGLT2 inhibitor) and a control one (combination of insulin and other antidiabetic tablets) which is calculated of -6.344% or 6.344% will be calculated with probability 0.8. The probability of a type I error if the null hypothesis is that the mean difference between the two groups is equal, is equivalent to 0.05.

Significance/future prospects:

This study is expected to open the horizons of better understanding the cardiovascular benefits of GLP-1 agonist, SGLT2 inhibitor and their combination in patients with type 2 diabetes mellitus. Moreover, the contribution of the investigator's results, in a clinical-level could be the use of new drug therapies that reduce both microvascular complications by reducing glycemia and macrovascular complications (myocardial infarction, stroke, cardiovascular mortality) as the first treatment line in patients with type 2 diabetes with high or very high cardiovascular risk.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Diabetes Mellitus, Type 2

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

No interventions assigned to this group

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.

No interventions assigned to this group

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.

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

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

Exclusion Criteria

* Subject has type 1 diabetes mellitus
* Subject has kidney disease
* Subject has retinopathy
Minimum Eligible Age

45 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Athens

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Ignatios Ikonomidis

Professor of Cardiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Ignatios Ikonomidis, Prof

Role: PRINCIPAL_INVESTIGATOR

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

Aimilianos N. Kalogeris, MD

Role: PRINCIPAL_INVESTIGATOR

2nd Department of Cardiology, University of Athens

John A. Thymis, MD

Role: PRINCIPAL_INVESTIGATOR

2nd Department of Cardiology,University of Athens

Vaia Lambadiari, Prof.

Role: PRINCIPAL_INVESTIGATOR

National and Kapodistrian University of Athens

Georgios Dimitriadis, Prof.

Role: STUDY_CHAIR

National and Kapodistrian University of Athens

Efstathios Iliodromitis, Prof.

Role: STUDY_CHAIR

National and Kapodistrian University of Athens

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

"Attikon" University General Hospital

Athens, Attica, Greece

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Greece

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Ignatios Ikonomidis, Prof.

Role: CONTACT

00306944805732

Aimilianos N. Kalogeris, MD

Role: CONTACT

00306949630300

References

Explore related publications, articles, or registry entries linked to this study.

Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, Ducimetiere P, Benetos A. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension. 2001 May;37(5):1236-41. doi: 10.1161/01.hyp.37.5.1236.

Reference Type RESULT
PMID: 11358934 (View on PubMed)

Handelsman Y, Bloomgarden ZT, Grunberger G, Umpierrez G, Zimmerman RS, Bailey TS, Blonde L, Bray GA, Cohen AJ, Dagogo-Jack S, Davidson JA, Einhorn D, Ganda OP, Garber AJ, Garvey WT, Henry RR, Hirsch IB, Horton ES, Hurley DL, Jellinger PS, Jovanovic L, Lebovitz HE, LeRoith D, Levy P, McGill JB, Mechanick JI, Mestman JH, Moghissi ES, Orzeck EA, Pessah-Pollack R, Rosenblit PD, Vinik AI, Wyne K, Zangeneh F. American association of clinical endocrinologists and american college of endocrinology - clinical practice guidelines for developing a diabetes mellitus comprehensive care plan - 2015. Endocr Pract. 2015 Apr;21 Suppl 1(Suppl 1):1-87. doi: 10.4158/EP15672.GL. No abstract available.

Reference Type RESULT
PMID: 25869408 (View on PubMed)

American Diabetes Association. 7. Approaches to Glycemic Treatment. Diabetes Care. 2016 Jan;39 Suppl 1:S52-9. doi: 10.2337/dc16-S010. No abstract available.

Reference Type RESULT
PMID: 26696682 (View on PubMed)

Jabbour SA, Hardy E, Sugg J, Parikh S; Study 10 Group. Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized, double-blind, placebo-controlled study. Diabetes Care. 2014;37(3):740-50. doi: 10.2337/dc13-0467. Epub 2013 Oct 21.

Reference Type RESULT
PMID: 24144654 (View on PubMed)

Nauck MA, Kemmeries G, Holst JJ, Meier JJ. Rapid tachyphylaxis of the glucagon-like peptide 1-induced deceleration of gastric emptying in humans. Diabetes. 2011 May;60(5):1561-5. doi: 10.2337/db10-0474. Epub 2011 Mar 23.

Reference Type RESULT
PMID: 21430088 (View on PubMed)

Shaefer CF Jr, Kushner P, Aguilar R. User's guide to mechanism of action and clinical use of GLP-1 receptor agonists. Postgrad Med. 2015;127(8):818-26. doi: 10.1080/00325481.2015.1090295. Epub 2015 Sep 15.

Reference Type RESULT
PMID: 26371721 (View on PubMed)

van Bloemendaal L, Ten Kulve JS, la Fleur SE, Ijzerman RG, Diamant M. Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS. J Endocrinol. 2014 Mar 7;221(1):T1-16. doi: 10.1530/JOE-13-0414. Print 2014 Apr.

Reference Type RESULT
PMID: 24323912 (View on PubMed)

Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B; EMPA-REG OUTCOME Investigators. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):323-34. doi: 10.1056/NEJMoa1515920. Epub 2016 Jun 14.

Reference Type RESULT
PMID: 27299675 (View on PubMed)

Ferrannini G, Hach T, Crowe S, Sanghvi A, Hall KD, Ferrannini E. Energy Balance After Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care. 2015 Sep;38(9):1730-5. doi: 10.2337/dc15-0355. Epub 2015 Jul 15.

Reference Type RESULT
PMID: 26180105 (View on PubMed)

Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):311-22. doi: 10.1056/NEJMoa1603827. Epub 2016 Jun 13.

Reference Type RESULT
PMID: 27295427 (View on PubMed)

Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17.

Reference Type RESULT
PMID: 26378978 (View on PubMed)

Frias JP, Guja C, Hardy E, Ahmed A, Dong F, Ohman P, Jabbour SA. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2016 Dec;4(12):1004-1016. doi: 10.1016/S2213-8587(16)30267-4. Epub 2016 Sep 16.

Reference Type RESULT
PMID: 27651331 (View on PubMed)

Chae CU, Pfeffer MA, Glynn RJ, Mitchell GF, Taylor JO, Hennekens CH. Increased pulse pressure and risk of heart failure in the elderly. JAMA. 1999 Feb 17;281(7):634-9. doi: 10.1001/jama.281.7.634.

Reference Type RESULT
PMID: 10029125 (View on PubMed)

Franklin SS, Khan SA, Wong ND, Larson MG, Levy D. Is pulse pressure useful in predicting risk for coronary heart Disease? The Framingham heart study. Circulation. 1999 Jul 27;100(4):354-60. doi: 10.1161/01.cir.100.4.354.

Reference Type RESULT
PMID: 10421594 (View on PubMed)

Domanski M, Norman J, Wolz M, Mitchell G, Pfeffer M. Cardiovascular risk assessment using pulse pressure in the first national health and nutrition examination survey (NHANES I). Hypertension. 2001 Oct;38(4):793-7. doi: 10.1161/hy1001.092966.

Reference Type RESULT
PMID: 11641288 (View on PubMed)

Meaume S, Benetos A, Henry OF, Rudnichi A, Safar ME. Aortic pulse wave velocity predicts cardiovascular mortality in subjects >70 years of age. Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):2046-50. doi: 10.1161/hq1201.100226.

Reference Type RESULT
PMID: 11742883 (View on PubMed)

Avolio AP, Deng FQ, Li WQ, Luo YF, Huang ZD, Xing LF, O'Rourke MF. Effects of aging on arterial distensibility in populations with high and low prevalence of hypertension: comparison between urban and rural communities in China. Circulation. 1985 Feb;71(2):202-10. doi: 10.1161/01.cir.71.2.202.

Reference Type RESULT
PMID: 3965165 (View on PubMed)

Vaitkevicius PV, Fleg JL, Engel JH, O'Connor FC, Wright JG, Lakatta LE, Yin FC, Lakatta EG. Effects of age and aerobic capacity on arterial stiffness in healthy adults. Circulation. 1993 Oct;88(4 Pt 1):1456-62. doi: 10.1161/01.cir.88.4.1456.

Reference Type RESULT
PMID: 8403292 (View on PubMed)

Ikonomidis I, Lekakis J, Papadopoulos C, Triantafyllidi H, Paraskevaidis I, Georgoula G, Tzortzis S, Revela I, Kremastinos DT. Incremental value of pulse wave velocity in the determination of coronary microcirculatory dysfunction in never-treated patients with essential hypertension. Am J Hypertens. 2008 Jul;21(7):806-13. doi: 10.1038/ajh.2008.172. Epub 2008 May 22.

Reference Type RESULT
PMID: 18497732 (View on PubMed)

Tzortzis S, Ikonomidis I, Lekakis J, Papadopoulos C, Triantafyllidi H, Parissis J, Trivilou P, Paraskevaidis I, Anastasiou-Nana M, Kremastinos DT. Incremental predictive value of carotid intima-media thickness to arterial stiffness for impaired coronary flow reserve in untreated hypertensives. Hypertens Res. 2010 Apr;33(4):367-73. doi: 10.1038/hr.2010.2. Epub 2010 Feb 5.

Reference Type RESULT
PMID: 20139923 (View on PubMed)

Ikonomidis I, Makavos G, Papadavid E, Varoudi M, Andreadou I, Gravanis K, Theodoropoulos K, Pavlidis G, Triantafyllidi H, Parissis J, Paraskevaidis I, Rigopoulos D, Lekakis J. Similarities in coronary function and myocardial deformation between psoriasis and coronary artery disease: the role of oxidative stress and inflammation. Can J Cardiol. 2015 Mar;31(3):287-95. doi: 10.1016/j.cjca.2014.11.002. Epub 2014 Nov 6.

Reference Type RESULT
PMID: 25660150 (View on PubMed)

Ikonomidis I, Pavlidis G, Lambadiari V, Kousathana F, Varoudi M, Spanoudi F, Maratou E, Parissis J, Triantafyllidi H, Dimitriadis G, Lekakis J. Early detection of left ventricular dysfunction in first-degree relatives of diabetic patients by myocardial deformation imaging: The role of endothelial glycocalyx damage. Int J Cardiol. 2017 Apr 15;233:105-112. doi: 10.1016/j.ijcard.2017.01.056. Epub 2017 Jan 8.

Reference Type RESULT
PMID: 28096045 (View on PubMed)

Ikonomidis I, Tzortzis S, Tsantes A, Ntai K, Triantafyllidi H, Trivilou P, Katsimaglis G, Dima K, Parissis J, Lekakis J. The interplay between renin-angiotensin system activation, abnormal myocardial deformation and neurohumoral activation in hypertensive heart disease: a speckle tracking echocardiography study. Int J Cardiovasc Imaging. 2017 Mar;33(3):323-329. doi: 10.1007/s10554-016-1010-1. Epub 2016 Oct 27.

Reference Type RESULT
PMID: 27787699 (View on PubMed)

Pieske B, Tschope C, de Boer RA, Fraser AG, Anker SD, Donal E, Edelmann F, Fu M, Guazzi M, Lam CSP, Lancellotti P, Melenovsky V, Morris DA, Nagel E, Pieske-Kraigher E, Ponikowski P, Solomon SD, Vasan RS, Rutten FH, Voors AA, Ruschitzka F, Paulus WJ, Seferovic P, Filippatos G. How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur J Heart Fail. 2020 Mar;22(3):391-412. doi: 10.1002/ejhf.1741. Epub 2020 Mar 5.

Reference Type RESULT
PMID: 32133741 (View on PubMed)

Ikonomidis I, Pavlidis G, Pliouta L, Katogiannis K, Maratou E, Thymis J, Michalopoulou E, Prentza V, Katsanaki E, Vlachomitros D, Kountouri A, Korakas E, Andreadou I, Kouretas D, Parissis J, Lambadiari V. Effects of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter-2 Inhibitors, and Their Combination on Neurohumoral and Mitochondrial Activation in Patients With Diabetes. J Am Heart Assoc. 2025 Mar 4;14(5):e039129. doi: 10.1161/JAHA.124.039129. Epub 2025 Feb 26.

Reference Type DERIVED
PMID: 40008510 (View on PubMed)

Ikonomidis I, Pavlidis G, Thymis J, Birba D, Kalogeris A, Kousathana F, Kountouri A, Balampanis K, Parissis J, Andreadou I, Katogiannis K, Dimitriadis G, Bamias A, Iliodromitis E, Lambadiari V. Effects of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter-2 Inhibitors, and Their Combination on Endothelial Glycocalyx, Arterial Function, and Myocardial Work Index in Patients With Type 2 Diabetes Mellitus After 12-Month Treatment. J Am Heart Assoc. 2020 May 5;9(9):e015716. doi: 10.1161/JAHA.119.015716. Epub 2020 Apr 24.

Reference Type DERIVED
PMID: 32326806 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2790/03-11-2017

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.