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

Bénédicte Gaborit1,2, Jean-Baptiste Julla3,4, Samaher Besbes5

  • 1Aix Marseille University, INSERM, INRA, C2VN, Marseille, France.

The Journal of Clinical Endocrinology and Metabolism
|October 8, 2019
PubMed
Abstract

Insights

Glucagon-like peptide 1 receptor agonists (GLP-1RA) do not affect angiogenesis or diabetic retinopathy (DR) severity. The AngioSafe study found no association between GLP-1RA exposure and severe DR in type 2 diabetes patients.

Area of Science:

  • Endocrinology
  • Ophthalmology
  • Vascular Biology

Background:

  • Conflicting trial results exist regarding the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR).
  • Understanding the role of GLP-1RA in angiogenesis is crucial for managing DR in type 2 diabetes (T2D).

Purpose of the Study:

  • To investigate the effect of GLP-1RA on angiogenesis using clinical and preclinical models in the AngioSafe T2D study.
  • To determine if GLP-1RA exposure is associated with the severity of DR in T2D patients.

Main Methods:

  • Two human studies: 1) Retrospective analysis of DR severity in T2D patients with varying GLP-1RA exposure. 2) Randomized trial assessing liraglutide's effect on hematopoietic progenitor cells (HPCs) and angio-miRNAs.
  • Experimental models: Exendin-4's effect on endothelial cell proliferation, survival, vascular morphogenesis in vitro, and ischemia-induced neovascularization in vivo.

Main Results:

  • No association was found between GLP-1RA exposure and severe DR in 3154 T2D patients (OR 1.139, P = .47).
  • Liraglutide had no significant effect on HPCs or angio-miRNAs.
  • Exendin-4 demonstrated no impact on endothelial cell function or retinal neovascularization in preclinical models.

Conclusions:

  • Clinical and preclinical data from the AngioSafe T2D study confirm that GLP-1RA do not influence angiogenesis.
  • GLP-1RA exposure is not associated with an increased risk of severe diabetic retinopathy in type 2 diabetes.
Keywords:
angiogenesisangiosafe Type 2 diabetes studyfundus photographyglucagon like peptide 1 receptor agonistretinopathytype 2 diabetes

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