GLP-1 Receptor Agonists Use and Incidence of Glaucoma: A Systematic Review and Meta-Analysis.

Purpose: In patients with diabetes, glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) 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 is a systematic review of the published literature regarding the incidence of glaucoma development in patients with type 2 diabetes treated with GLP-1 RAs compared with 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 nonusers. We calculated the pooled hazard ratio for the GLP-1 RA group and control individuals using a random-effects model.

Results: One hundred ninety-four studies were identified, of which 5 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 with control individuals (hazard ratio 0.779 [95% CI 0.585-11.036]; P = .086; I = 86%). During the leave-one-out sensitivity analysis, the inclusion of the study by Shao and associates 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 with control individuals, with reduced heterogeneity (hazard ratio 0.71 [95% CI 0.60-0.85], I² = 29%). Studies had moderate bias concerns because of confounding factors and intervention classification.

Conclusion: 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.