Association of sodium-glucose cotransporter 2 inhibitors with glaucoma risk in patients with type 2 diabetes: a systematic review and meta-analysis of observational studies

Abstract Background Type 2 diabetes mellitus (T2DM) is an established risk factor for glaucoma, and their coexistence increases the risk of visual impairment. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are widely used glucose-lowering agents with well‑recognized cardiometabolic and renal benefits. Emerging evidence suggests that SGLT2i may exert potential ocular protective effects through mechanisms including intraocular pressure reduction, attenuation of oxidative stress, and improvement of microvascular function. However, epidemiological findings regarding the association between SGLT2i use and glaucoma risk in patients with T2DM remain inconsistent. We therefore conducted a systematic review and meta-analysis to synthesize the available evidence and evaluate the association between SGLT2i use and the risk of glaucoma and glaucoma-related outcomes in this population. Methods A comprehensive literature search was conducted in PubMed, Embase, Web of Science, and the Cochrane Library from database inception to June 1, 2026. Observational studies reporting the association between SGLT2i exposure and incident glaucoma or glaucoma-related outcomes in patients with T2DM were eligible for inclusion. Two reviewers independently screened studies, extracted data, and assessed methodological quality. Adjusted hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were pooled using random-effects models. Statistical analyses were conducted using Review Manager software. Results The included studies comprised large-scale real-world cohorts, encompassing over 3.1 million individuals with T2DM across all cohorts. The pooled analysis showed that SGLT2i use was significantly associated with a lower risk of overall glaucoma (HR = 0.86, 95% CI 0.77–0.96, P = 0.008). When individual glaucoma-related outcomes were examined, SGLT2i use was associated with lower risks of primary open-angle glaucoma (POAG) (HR = 0.83, 95% CI 0.75–0.92, P = 0.0007) and ocular hypertension (OHT) (HR = 0.84, 95% CI 0.75–0.95, P = 0.004). In an exploratory analysis based on very limited data, no statistically significant association was observed for primary angle-closure glaucoma (PACG) (HR = 0.81, 95% CI 0.44–1.51, P = 0.51); however, this finding should be interpreted with great caution given the substantial heterogeneity and the very small number of included comparisons. Conclusions Current evidence suggests that SGLT2i use is associated with a lower risk of overall glaucoma in patients with T2DM, with consistent associations observed for POAG and OHT. The association with PACG remains uncertain and is based on exploratory analyses. Given the observational nature of the included studies and the potential for residual confounding, large-scale, multicenter, prospective studies are warranted to validate these findings.