Comprehensive review of glucagon-like peptide 1 receptor agonist treatment on the risk of cardiovascular outcomes and retinopathy as diabetic complications.

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Cardiovascular and microvascular disorders are serious complications of diabetes. Intensive glucose control is believed to hinder the pathological progression of these complications. In this review, we focus on the risk of diabetic retinopathy (DR) under intensive treatment with recently introduced glucose-lowering drugs, including glucagon-like peptide 1 receptor agonists (GLP-1RAs), sodium-glucose co-transporter-2 (SGLT2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors. GLP-1RAs are more suitable for patients with diabetes at risk for, or established, cardiovascular complications, while SGLT2 inhibitors are more appropriate for complications of heart failure and chronic renal diseases. Accumulating evidence indicates that GLP-1RAs may provide a greater reduction in the risk of DR in patients with diabetes compared to DPP-4 inhibitors, sulfonylureas, or insulin. GLP-1RAs may be ideal antihyperglycemic drugs with direct benefits for the retina, since GLP-1R can be expressed in photoreceptors. Topical administration of GLP-1RAs induces direct retinal neuroprotection against DR by multiple mechanisms, such as preventing both neurodysfunction and retinal neurodegeneration; relieving the disruption of the blood-retinal barrier and associated vascular leakage, and inhibiting oxidative stress, inflammatory action, and neuronal apoptosis. Hence, it seems reasonable to utilize this strategy to treat patients with diabetes and early-stage DR, rather than exclusively using neuroprotective agents.