Diabetic Retinopathy, Endothelial Dysfunction, GLP-1, Microvascular Circulation, Retinal Vascular Diseases, SGLT 2 Inhibitors
Conditions
Keywords
diabetic retinopathy, Retinal Vascular Diseases, GLP-1, SGLT 2 inhibitors, Microvascular Circulation, type 2 Diabetes Mellitus
Brief summary
ARIADNE is a prospective observational cohort study of patients with type 2 diabetes mellitus (T2DM) treated with daily metformin and scheduled to initiate treatment with newer antidiabetic agents, such as sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) and glucagon-like peptide-1 receptor agonists (GLP-1RAs). These newer antidiabetic agents have demonstrated significant benefits in improving glycaemic control; however, some studies suggest that their rapid glucose-lowering effects may be associated with transient worsening or progression of retinal complications. The purpose of this study is to evaluate the efficacy and safety of newer antidiabetic agents on retinal vasculature and visual acuity, and to investigate how these changes are associated with alterations in markers of peripheral endothelial and cardiovascular function.
Detailed description
The investigators will study individuals with type 2 diabetes mellitus (T2DM), diagnosed according to the criteria established by the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA), with and without diabetic retinopathy, who are receiving metformin therapy. Participants will receive, in addition to metformin, either glucagon-like peptide-1 receptor agonists (GLP-1RAs) or sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors). At treatment initiation (t0) and 12 months after initiation (t1), blood samples, ocular function, peripheral endothelial function, and cardiovascular function will be evaluated. This study will include 40 participants: i) 20 participants treated with metformin and GLP-1RAs; ii) 20 participants treated with metformin and SGLT2 inhibitors.
Interventions
None listed
Sponsors
University of Athens
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Individuals aged ≥18 years. 2. Male and/or female patients with T2DM diagnosed according to the criteria established by the EASD and the ADA. 3. Patients receiving only metformin as antidiabetic treatment. 4. Patients who have not previously received SGLT2 inhibitors or GLP-1 receptor agonists. 5. Patients who are able to provide informed consent for participation in the study.
Exclusion criteria
1. Patients who are pregnant or breastfeeding. 2. History of multiple severe hypoglycaemic episodes during the past two years. 3. History of ketoacidosis or metabolic acidosis. 4. Active intraocular inflammation in either eye, such as infectious conjunctivitis, keratitis, scleritis, endophthalmitis, or autoimmune uveitis. 5. Patients who have undergone panretinal photocoagulation within the last 6 months. 6. Patients who have received intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy or corticosteroids within the last 6 months. 7. Patients who have undergone cataract surgery or vitrectomy within the last 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Ocular Parameters | Changes from baseline to 12-month follow-up. | Change in Best-Corrected Visual Acuity (BCVA): Assessment of changes in best-corrected visual acuity (BCVA) using standardized Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Retinal Thickness Parameters | Changes from baseline to 12-month follow-up. | Change in Retinal Thickness Parameters Assessed by Optical Coherence Tomography (OCT): Assessment of changes from baseline in central subfield thickness (CST), parafoveal retinal thickness, and perifoveal retinal thickness using spectral-domain optical coherence tomography (SD-OCT), reported in micrometers (µm). |
| Change in Retinal Microvascular Parameters | Changes from baseline to 12-month follow-up. | Change in Retinal Microvascular Parameters Assessed by Optical Coherence Tomography Angiography (OCT-A): Evaluation of changes from baseline in retinal vessel density and retinal capillary perfusion using optical coherence tomography angiography (OCT-A), reported as percentage (%), and foveal avascular zone (FAZ) area, reported in square millimeters (mm²). |
| Changes in Endothelial Glycocalyx function | Changes from baseline to 12-month follow-up. | Change in Endothelial Glycocalyx Thickness Assessed by Perfused Boundary Region (PBR 5-25): Evaluation of changes from baseline in endothelial glycocalyx thickness using perfused boundary region (PBR 5-25) measurements obtained by sublingual microvascular imaging, reported in micrometers (µm). Increased PBR values will be assessed as markers of endothelial dysfunction and microvascular impairment. |
| Change in Arterial Stiffness | Changes from baseline to 12-month follow-up. | Change in Carotid-Femoral Pulse Wave Velocity (cf-PWV): Assessment of changes from baseline in arterial stiffness using carotid-femoral pulse wave velocity (cf-PWV), reported in meters per second (m/s). |
Countries
Greece
Outcome results
None listed