Ocular Complications of SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors in T2DM Treatments: A Retrospective Real-World Cohort Study

Abstract

Glaucoma is a leading cause of irreversible vision loss worldwide, and type 2 diabetes mellitus (T2DM) is increasingly recognized as a risk factor for glaucoma. This study compared the effects of 3 classes of antidiabetic drugs-sodium-glucose cotransporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase 4 inhibitors (DPP-4is)-on ocular and systemic complications in adults with T2DM. Using the TriNetX database from 2015 to 2025, adults aged ≥ 40 years initiating SGLT-2is, GLP-1 RAs, or DPP-4is were identified and matched through propensity score methods to create three cohorts. The primary outcomes included open-angle glaucoma and ocular hypertension, with secondary outcomes of cataract, diabetic retinopathy, macular edema, and various systemic events. The matched cohorts included 68,283 patients (SGLT-2is vs. GLP-1 RAs), 69,765 patients (SGLT-2is vs. DPP-4is), and 55,760 patients (GLP-1 RAs vs. DPP-4is). Compared with GLP-1 RAs and DPP-4is, SGLT-2i use was associated with significantly lower risks of open-angle glaucoma (HR: 0.88 and 0.90), ocular hypertension (HR: 0.78 and 0.90), cataract (HR: 0.84 and 0.87), diabetic retinopathy (HR: 0.84 and 0.87), and macular edema (HR: 0.77 and 0.71). Conversely, GLP-1 RAs demonstrated stronger protective effects against systemic complications, such as diabetic nephropathy or chronic kidney disease, liver cirrhosis, dementia, cerebral infarction, and ischemic heart disease. These findings suggest that SGLT-2is may be prioritized in T2DM patients at higher risk for ocular complications, while GLP-1 RAs may be preferred when systemic risk reduction is the primary therapeutic goal.