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

Kathleen Eng; Nazlee Zebardast; Michael V Boland; Jui-En Lo; Swarup S Swaminathan; David S Friedman; Kevin Sheng-Kai Ma

doi:10.1016/j.ajo.2024.10.029

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

Am J Ophthalmol. 2024 Nov 6:271:286-298. doi: 10.1016/j.ajo.2024.10.029. Online ahead of print.

Authors

Kathleen Eng¹, Nazlee Zebardast², Michael V Boland³, Jui-En Lo⁴, Swarup S Swaminathan⁵, David S Friedman⁶, Kevin Sheng-Kai Ma⁷

Affiliations

¹ From Harvard Medical School (K.E.), Boston, Massachusetts. Electronic address: [email protected].
² Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School (N.Z., M.V.B., and D.S.F.), Boston, Massachusetts.
³ Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School (N.Z., M.V.B., and D.S.F.), Boston, Massachusetts; Glaucoma Center of Excellence (M.V.B. and D.S.F.), Boston, Massachusetts.
⁴ Department of Internal Medicine, MetroHealth Medical Center, Case Western Reserve University (J.L.), Cleveland, Ohio.
⁵ Bascom Palmer Eye Institute, University of Miami Miller School of Medicine (S.S.S.), Miami, Florida.
⁶ Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School (N.Z., M.V.B., and D.S.F.), Boston, Massachusetts; Glaucoma Center of Excellence (M.V.B. and D.S.F.), Boston, Massachusetts. Electronic address: [email protected].
⁷ Center for Global Health, Perelman School of Medicine, University of Pennsylvania (K.S.M.), Philadelphia, Pennsylvania. Electronic address: [email protected].

PMID: 39515454
DOI: 10.1016/j.ajo.2024.10.029

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.