GLP-1 RECEPTOR AGONISTS USE AND INCIDENCE OF GLAUCOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS: GLP-1 receptor agonists use and incidence of glaucoma.

Introduction: In diabetics, glucagon-like peptide 1 (GLP-1) receptor agonists (RA) may protect against microvascular alterations and oxidative stress, both of which have been implicated in glaucoma. Multiple studies suggest a possible relation between GLP-1 RA use and the development of glaucoma. This study performs a systematic review of the literature regarding the incidence of glaucoma development in type 2 diabetes patients treated with GLP-1 receptor agonists compared to a control group.

Design: A systematic review and meta-analysis.

Methods: We searched PubMed, Embase, Web of Science, and Cochrane databases from July 1991 to May 2024 for studies comparing the incidence of glaucoma development in GLP-1 RA users versus non-users. We calculated the pooled HR for the GLP-1 RA group and control using a random-effects model.

Results: 194 studies were identified, of which five retrospective studies met the inclusion criteria, with a total of 156,042 participants based on routinely collected electronic data. The meta-analysis revealed no significant statistical difference in glaucoma incidence among GLP-1 RA users compared to controls (HR 0.779; 95% CI [0.585; 1.036]; p=0.086; I=86%). During the leave-one-out sensitivity analysis, the inclusion of Shao et al. yielded opposite effects, suggesting that SGLT-2 inhibitors might be as effective as, or potentially more effective than GLP-1 RAs in preventing glaucoma. When this study was excluded from the analysis, the results demonstrated a significant reduction in the incidence of glaucoma among GLP-1 RA users compared to controls, with reduced heterogeneity (HR 0.71; 95% CI [0.60, 0.85], I² = 29%). Studies had moderate bias concerns due to confounding factors and intervention classification.

Conclusions: This systematic meta-analysis found that GLP-1 RA use is associated with reduced glaucoma development in retrospective studies. Future, well-designed, long-term studies focusing on GLP-1 RAs and SGLT-2 inhibitors are needed to validate these findings and evaluate their effects on glaucoma progression and vision loss. The overall interpretation should be cautious.