Sodium-Glucose Cotransporter 2 Inhibitors for the Primary Prevention of Glaucoma in Patients With Type 2 Diabetes: A Target Trial Emulation

Abstract

PURPOSE

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

DESIGN

Target trial emulation using observational data from multiple healthcare organizations.

METHODS

This population-based cohort study included 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. Propensity score matching was conducted to control for sociodemographic characteristics comorbidities, and concomitant use of medications. The exposure considered was treatment with SGLT2i for type 2 diabetes, and the outcomes were new-onset glaucoma and its subtypes after initiation of antidiabetic treatments. Subgroup analyses were performed to evaluate the effect of individual SGLT2i on incident glaucoma.

RESULTS

After propensity score matching, 722,446 patients were included in the SGLT2i arm and the DPP4i arm, respectively. Patients on SGLT2i, compared with those on DPP4i, had a lower risk of glaucoma (hazard ratio [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 0.702, 95% CI 0.636, 0.781). 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), dapagliflozin (HR 0.814, 95% CI 0.774, 0.855), and canagliflozin (HR 0.893, 95% CI 0.862, 0.926). 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, including canagliflozin, empagliflozin, dapagliflozin, and ertugliflozin, had a significantly lower risk of incident glaucoma compared to those on DPP4i. SGLT2i demonstrated a protective effect for both open-angle glaucoma and angle-closure glaucoma.