Sodium-Glucose Cotransporter 2 Inhibitors for the Primary Prevention of Glaucoma in Patients With Type 2 Diabetes: A Target Trial Emulation.
Eng Kathleen, Zebardast Nazlee, Boland Michael V, Lo Jui-En, Swaminathan Swarup S, Friedman David S, Ma Kevin Sheng-Kai
AI Summary
SGLT2 inhibitors significantly lowered glaucoma risk in type 2 diabetes patients compared to other diabetes drugs, suggesting a potential protective effect against both open-angle and angle-closure glaucoma.
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.
MeSH Terms
Shields Classification
Key Concepts4
Patients with type 2 diabetes treated with sodium-glucose cotransporter 2 inhibitors (SGLT2i) had a lower risk of glaucoma (HR 0.815, 95% CI 0.794, 0.837) compared to those on dipeptidyl peptidase 4 inhibitors (DPP4i).
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) demonstrated a lower risk for 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) in patients with type 2 diabetes compared to dipeptidyl peptidase 4 inhibitors (DPP4i).
Among individual sodium-glucose cotransporter 2 inhibitors (SGLT2i), ertugliflozin (HR 0.668, 95% CI 0.512, 0.871) was associated with the lowest risk of glaucoma in patients with type 2 diabetes, 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 sodium-glucose cotransporter 2 inhibitors (SGLT2i) on glaucoma risk was validated in patients with type 2 diabetes when compared with glucagon-like peptide-1 receptor agonists (GLP1RA) (HR 0.932, 95% CI 0.906, 0.959).
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