Ophthalmological Side-Effects of Glucagon-Like Peptide Receptor Agonists
Abstract
Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become an essential component in the treatment of type 2 diabetes mellitus and obesity due to their potent glucose-lowering effects and cardiovascular benefits. However, increasing clinical use has raised concerns regarding their potential ophthalmological side effects, particularly diabetic retinopathy, diabetic macular oedema, and neuroophthalmological complications such as nonarteritic anterior ischemic optic neuropathy (NAION).
Methods: This narrative review summarizes current evidence regarding the ophthalmological safety profile of GLP-1 receptor agonists. Relevant clinical trials, meta-analyses, observational studies, and experimental data were evaluated to assess the incidence, risk factors, and potential mechanisms underlying ocular complications associated with GLP-1 RA therapy.
Main findings: Available evidence suggests that GLP-1 receptor agonists are not directly retinotoxic; however, transient worsening of diabetic retinopathy has been observed, particularly in patients with pre-existing retinal disease, high baseline HbA1c, and rapid glycaemic improvement. Most studies indicate a neutral effect on diabetic macular oedema incidence, although differences between drug classes and individual patient risk profiles have been reported. Emerging data suggest a possible association between semaglutide and NAION, although absolute risk remains low and causality has not been definitively established. Proposed mechanisms include rapid glycemic normalization, altered microvascular perfusion, endothelial dysfunction, and vascular autoregulatory changes.
Principal conclusion: GLP-1 receptor agonists remain highly effective and generally safe therapeutic agents, with ophthalmological risks primarily related to rapid metabolic improvement rather than direct drug toxicity. Careful patient selection, gradual glycemic optimization, and appropriate ophthalmological monitoring are recommended, particularly in patients with pre-existing microvascular disease.
