Assessment of Retinal-Angio Findings In Patients With Diabetes Type II Treated With Novel Antidiabetic Therapies (ARIADNE)

Assessment of Retinal-Angio Findings in Patients With Diabetes Type II Treated With Novel Antidiabetic Therapies

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetic Retinopathy; Endothelial Dysfunction; Microvascular Circulation; GLP-1; SGLT 2 Inhibitors; Retinal Vascular Diseases

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.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Greece
  • Attica
    • Athens, Attica, Greece, 12462
      • 2nd Department of Ophthalmology, Attikon University Hospital, National and Kapodistrian University of Athens

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals with type 2 diabetes mellitus (T2DM), diagnosed according to the criteria established by the EASD and the ADA, with and without diabetic retinopathy, who are receiving metformin therapy. Participants will receive, in addition to metformin, either GLP-1 receptor agonists (GLP-1RAs) or sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors).

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
GLP-1RAs; Subjects will take GLP-1RAs
SGLT2-i; Subjects will take SGLT2-i

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Ocular Parameters	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.	Changes from baseline to 12-month follow-up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Retinal Thickness Parameters	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).	Changes from baseline to 12-month follow-up.
Change in Retinal Microvascular Parameters	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 from baseline to 12-month follow-up.
Changes in Endothelial Glycocalyx function	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.	Changes from baseline to 12-month follow-up.
Change in Arterial Stiffness	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).	Changes from baseline to 12-month follow-up.

Collaborators and Investigators

• Sponsor: University of Athens

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Actual): January 30, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: April 24, 2026
• First Submitted That Met QC Criteria: May 18, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: GLP-1; diabetic retinopathy; type 2 Diabetes Mellitus; Microvascular Circulation; Retinal Vascular Diseases; SGLT 2 inhibitors
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Eye Diseases; Diabetic Angiopathies; Diabetes Complications; Retinal Diseases; Nutritional and Metabolic Diseases; Diabetic Retinopathy; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 137-16/02/2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No