Are GLP-1 receptor agonists and diabetic retinopathy foes or friends?

With the increasing number of patients with diabetes worldwide, the number of patients with diabetic retinopathy (DR) is also increasing, which affects the lives of patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are anti-diabetic drugs that mimic the action of endogenous glucagon-like peptide-1, which significantly improve glycemic control in patients with type 2 diabetes. GLP-1RAs can repair the blood-retinal barrier function by activating the GLP-1 receptor in retinal endothelial cells and nerve cells, inhibiting the RhoA/ROCK signaling pathway, up-regulating the tight junction protein occludin and ZO-1, and inhibiting the activation of microglia, reducing the release of pro-inflammatory factors, and reducing neuroinflammation and vascular leakage. However, some GLP-1RAs may increase the risk of DR, such as diabetic macular edema and proliferative DR, and may increase the risk of DR deterioration, especially during rapid glucose lowering. Although the new GLP-1/GIP dual-receptor agonists and GLP-1/GIP/glucagon tri-receptor agonists show comprehensive benefit potential by effectively improving body metabolism, the short-term negative effect of sudden blood glucose drop still needs to be paid attention to. For patients with moderate to severe DR, it is necessary to strengthen ophthalmic monitoring to avoid rapid blood glucose decline in the initial treatment. In the long-term treatment, metabolic benefits and retinal risks need to be weighed, and the patient's condition needs to be evaluated before treatment. Therefore, GLP-1RAs has a duality of "mechanism protection and clinical risk" on DR, and individualized treatment strategy should take into consideration drug characteristics, DR severity and glucose control.