Incretin-mimetic Hypoglycemic Drugs and Severe Retinopathy

Study Overview
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Brief Summary
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Experimental data suggest that GLP-1 promote endothelial cell growth and angiogenesis which may have beneficial effects on the cardiovascular system but harmful effects on the retina . This project investigate the possible link between incretin therapy and Severe Diabetic Retinopathy. The prevalence of severe DR in patients exposed to incretin therapy (GLP-1 analogs or DPP4 inhibitors) is compared to that in non-exposed patients to these antidiabetic classes.

Detailed Description
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This study is dedicated to investigate the impact of routinely prescribed hypoglycaemic treatments on the prevalence of severe retinopathy and to seek possible biomarkers of severe retinopathy. Hypoglycemic treatments taken by the patients are those prescribe by the usuel diabetogist in the context of routine care. The study includes T2D patients according to ADA criteria treated with any kind of hypoglycemic treatment and attending a diabetes center (three in Marseille: Department of Endocrinology, Hôpital Nord, Assistance Publique des Hôpitaux de Marseille and Service d'Ophtalmologie, Hôpital Saint-Joseph and Service de Diabétologie, Hôpital Saint-Joseph, and two in Paris : Centre Universitaire du Diabète et de ses Complications Hôpital Lariboisière, Université Paris 7, Assistance Publique des Hôpitaux de Paris and Service d'Endocrinologie, Diabétologie et Nutrition, Hôpital Bichat). It consists of two visits: Visits1 Inclusion and Visits 2 three years after the inclusion. In each visit, the investigators will collect results of eye examination (fundus) and annual diabetes check up including anthropometric data, routine biology, diabetes complication status as well as medications taken by the patients (past and current). A bio-banking (blood, urine and hairs) will be also collected. Primary objective : to compare the prevalence of severe DR in patients exposed to incretin therapy (GLP-1 analogs or DPP4 inhibitors) to that in non-exposed patients at baseline. Secondary objective: To compare the proportion of patients who worsen DR between V1 (inclusion) and V2 (after 3-yr of treatment) in patients exposed to incretin-based therapy from baseline vs non-exposed patients: patients with no DR or mild to moderate non proliferative DR at V1 who progress to severe DR at V2. To evaluate whether the concentrations of angiogenic/inflammatory molecules and circulating endothelial and inflammatory cells are associated with severe DR in relation with the use of GLP-1 based therapy at V1 and V2.

Official Title
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Impact of Incretin-mimetic Hypoglycaemic Drugs on Diabetic Retinopathy in Type 2 Diabetic Patients and Study of Biomarkers in the Development of Severe Retinopathy: Angiosafe-T2D Study 2

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Other: 1: incretin-based therapy
* Other: 2: other antidiabetic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T2D patients according to ADA criteria treated with any kind of hypoglycaemic treatment Age above 18 years Exclusion Criteria: Type 1 diabetes Patients with cataract preventing DR grading Patients who had panretinal photocoagulation more than 10 years ago Documented pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1: incretin-based therapy<br>Patients with incretin-based therapy | Other: 1: incretin-based therapy<br> <br> |
| Other: 2: other antidiabetic<br>Patients with other antidiabetic | Other: 2: other antidiabetic<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of Severe DR at V1 (inclusion) | Retinography | at inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of severe DR at V2 (after 3 years of treatment) | Retinography | after 3 years | 
| Plasma concentrations of ANGPT4 |  | at inclusion and 3 years | 
| Plasma concentrations of VEGF |  | at inclusion and 3 years | 
| Plasma concentrations of proinflammatory cytokines such as IL-1beta, IL-6, IL-8, TNF-alpha |  | at inclusion and 3 years | 
| Concentrations of blood circulating EPCs and PBMCs |  | at inclusion and 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Incretin-based therapy, GLP1, Angiogenesis Inflammation, Hypoglycaemic treatment