Metformin Use and Risk of Glaucoma: A Systematic Review and Meta-analysis.

TOPIC

To evaluate whether metformin use is associated with a reduced risk of developing glaucoma.

CLINICAL RELEVANCE

Glaucoma is a leading cause of irreversible blindness worldwide. Identifying systemic medications that may modify glaucoma risk could have important implications for prevention strategies in patients with diabetes, a population frequently treated with metformin.

METHODS

This systematic review and meta-analysis of observational cohort studies, registered on PROSPERO (CRD420250655975), was done through PubMed, Scopus, Web of Science, and Google Scholar until June 16, 2025. Eligible studies compared glaucoma incidence among metformin users versus non-users or users of other antidiabetic drugs (ADDs). Risk of bias was assessed using the Newcastle-Ottawa Scale. Binary outcomes were pooled using random-effects models to calculate odds ratios (ORs), and time-to-event outcomes were synthesized using hazard ratios (HRs). Subgroup analyses explored confounder adjustment methods and comparator types. Certainty of evidence was graded using GRADE framework.

RESULTS

Twelve retrospective cohort studies (n=1,247,325; 732,423 metformin users; 513,292 controls) were included. The pooled crude OR showed no association between metformin use and glaucoma risk (OR=0.96; 95%CI, 0.87-1.06; I²=79.14%; low certainty). A leave-one-out sensitivity analysis excluding a study with a non-metformin active comparator resulted in a modest but significant reduction in risk (OR=0.92; 95%CI, 0.87-0.98; low to moderate certainty). No effect modification was detected by the confounder adjustment method (propensity-score matched vs. regression; p=0.20; low certainty) or comparator type (no metformin vs. other ADDs; p=0.34; very low certainty). The follow-up duration did not significantly modify the effects. Four studies contributed time-to-event analyses: pooled unadjusted HR indicated a lower risk among metformin users (HR=0.86; 95%CI, 0.79-0.93; I²=0%; moderate certainty), which persisted in adjusted models (aHR=0.88; 95%CI, 0.80-0.96; I²=0.01%; moderate certainty). There was no evidence of small-study effects (Egger's p=0.955).

CONCLUSION

Across observational cohorts, metformin use was not associated with a reduced glaucoma risk in crude analyses; however, sensitivity analyses suggested a possible protective effect. Time-to-event analyses consistently demonstrated a modest reduction in glaucoma risk, supported by moderate-certainty evidence after adjusting for confounders. Overall, certainty of evidence ranged from very low (comparator analyses) to moderate (time-to-event analyses).