Ocular Outcomes of Glucagon-Like Peptide-1 Receptor Agonists Versus Sodium-Glucose Cotransporter-2 Inhibitors in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Real-World Evidence

While sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) offer proven cardiometabolic benefits, clinical evidence regarding their comparative ocular safety remains complex and contradictory.This study aimed to evaluate the ocular outcomes of SGLT2is versus GLP-1RAs in patients with type 2 diabetes.We conducted a systematic literature search across PubMed, Scopus, and CENTRAL through September 2026 and identified active-comparator real-world cohort studies comparing SGLT2is and GLP-1RAs in diabetic adults.The primary outcome evaluated was proliferative diabetic retinopathy (PDR) progression.Secondary outcomes included diabetic macular edema (DME) and nonarteritic anterior ischemic optic neuropathy (NAION).Random-effects models were utilized to calculate pooled risk ratios (RRs) with 95% confidence intervals (CIs).Risk of bias was assessed using the Risk of Bias in Non-randomized Studies -of Interventions (ROBINS-I) tool.Four real-world cohort studies provided quantitative data for meta-analytic synthesis.Pooled analysis demonstrated no statistically significant difference in PDR progression risk between GLP-1RA and SGLT2i initiation (RR = 1.08, 95% CI: 0.95-1.23,p = 0.25; I² = 93%).However, GLP-1RA initiation was associated with a statistically significant 48% increased risk of DME (RR = 1.48, 95% CI: 1.36-1.62,p < 0.00001; I² = 69%) and a 39% increased risk of NAION (RR = 1.39, 95% CI: 1.20-1.60,p < 0.00001; I² = 0%) compared to SGLT2i initiation.In conclusion, while overall PDR progression risk remains comparable between drug classes, GLP-1RA initiation is associated with significantly higher risks of DME and NAION relative to SGLT2i initiation.Individualized ocular risk profiles should be evaluated when selecting second-line antidiabetic agents.