Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study

Bénédicte Gaborit 1 2, Jean-Baptiste Julla 3 4, Samaher Besbes 5, Matthieu Proust 5, Clara Vincentelli 1 2, Benjamin Alos 5, Patricia Ancel 1, Fawaz Alzaid 4, Rodrigue Garcia 5, Philippe Mailly 5, Florence Sabatier 1, Maud Righini 6, Pierre Gascon 6 7, Frédéric Matonti 6 7, Marie Houssays 8, Louisa Goumidi 1, Lucile Vignaud 9, Xavier Guillonneau 9, Ali Erginay 10, Bénédicte Dupas 10, Jennifer Marie-Louise 10, Marianne Autié 10, Tiphaine Vidal-Trecan 3, Jean-Pierre Riveline 3 4, Nicolas Venteclef 4, Pascale Massin 10, Laurent Muller 5, Anne Dutour 1 2, Jean-François Gautier 3 4, Stéphane Germain 5

Main idea: The AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR.

Abstract

Aims: Recent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR). The aim of the AngioSafe type 2 diabetes (T2D) study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models.

Methods: We performed two studies in humans. In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR, as diagnosed with retinal imaging. We then studied the experimental effect of Exendin-4, on key steps of angiogenesis.

Results: In a cohort of 3154 T2D patients, 10% displayed severe DR. Sex, disease duration, glycated hemoglobin (HbA1c), micro- and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR, while no association was found with GLP-1RA exposure. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells.

Source NIH