Sodium-glucose cotransporter 2 inhibitors and glaucoma in patients with type 2 diabetes.

Purpose: Pleiotropic cardiovascular benefits of sodium glucose co-transporter 2 inhibitors (SGLT2i) have been demonstrated in patients with type 2 diabetes mellitus due to vascular remodeling effects. It is unclear whether a similar benefit may be seen for glaucoma. The purpose of this study is to assess the effect of SGLT2i on the risk of glaucoma in patients with type 2 diabetes.

Design: Target trial emulation using a population-based, propensity score-matched clinical cohort approach.

Methods: Setting: Population-based, propensity score-matched clinical cohort study.

Study population: Adults with type 2 diabetes in the United States who newly initiated treatment with SGLT2i, dipeptidyl peptidase 4 inhibitors (DPP4i), or glucagon-like peptide-1 receptor agonists (GLP1RA) between 2013 and 2023. After propensity score matching, 722,446 patients were included in the SGLT2i arm and the DPP4i arm, respectively. Participants were matched based on age at index, race and sex, comorbidities, and concomitant use of medications.

Exposure: Treatment with SGLT2i for type 2 diabetes.

Main outcome measure(s): Incidence of new-onset glaucoma and its subtypes after initiation of SGLT2i, DPP4i, or GLP1RA. Subgroup analyses were performed to demonstrate the effect of individual SGLT2i on incident glaucoma.

Results: Patients on SGLT2i compared to those on DPP4 had a lower risk of glaucoma (HR: 0.815, 95% confidence interval [CI]: 0.794, 0.837), including open-angle glaucoma (HR: 0.755, 95%CI: 0.729, 0.781) and primary angle-closure glaucoma (HR: 0.592, 95%CI: 0.540, 0.650). Among all SGLT2i, ertugliflozin (HR: 0.668, 95%CI: 0.512, 0.871) was associated with the lowest risk of glaucoma, followed by empagliflozin (HR: 0.727, 95%CI: 0.696, 0.759), then dapagliflozin (HR: 0.814, 95%CI: 0.774, 0.855). The protective effect of SGLT2i on glaucoma was validated when compared with GLP1RA (HR: 0.932, 95%CI: 0.906, 0.959).

Conclusions: Patients on SGLT2i, especially ertugliflozin and empagliflozin, had a significantly lower risk of incident glaucoma compared to those on DPP4i, an association that was less robust but significant in a sensitivity analysis using GLP1RA as the active comparator. SGLT2i had a protective effect for both open-angle glaucoma and angle-closure glaucoma.