Evaluating the Ocular Safety Profile of Glucagon-Like Peptide-1 Receptor Agonists

Background The use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) has surged, yet their ocular safety profile remains inconclusive. This paper evaluates the ocular safety of GLP-1RAs regarding neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), and glaucoma in a global cohort. Methods We conducted three parallel, retrospective, new-user, propensity-score-matched (PSM) cohort studies using the TriNetX Global Federated Health Research Network. New users of GLP-1RAs with type 2 diabetes were matched 1:1 to new users of SGLT-2 inhibitors (for nAMD and DR analyses) or DPP-4 inhibitors (for the glaucoma analysis). The models controlled for 77 covariates including demographics, comorbidities, labs, and healthcare utilization proxies. Hazard Ratios (HRs) were calculated using Cox proportional hazards models, with a secondary, time-stratified, exploratory analysis for glaucoma outcomes to address unequal follow-up. Results Matched cohorts included 951 pairs (nAMD), 210,027 pairs (glaucoma), and 8,006 pairs (DR). GLP-1RA use was not associated with an increased risk of nAMD or DR progression (all P > 0.05). For glaucoma, a time-stratified analysis revealed no significant difference in procedural risk at two years (HR 0.88; 95% CI, 0.60–1.29); however, a significant reduction in the risk of a new glaucoma diagnosis was observed (HR 0.80; 95% CI, 0.65–0.98; P = 0.03). Conclusion In this global analysis, GLP-1RAs demonstrated a favorable ocular safety profile. The findings suggest a potential neuroprotective effect against glaucoma diagnosis, validating signals previously observed in US-based cohorts.