PURPOSE: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist (GLP-1 RA), has shown superior efficacy in glycemic control, weight loss, and cardiometabolic outcomes compared to GLP-1 RAs alone. While GLP-1 RAs may offer neuroprotective effects relevant to glaucoma, the impact of dual-incretin therapies like tirzepatide on glaucoma remains unknown. This study investigates the association between tirzepatide initiation and the risk of primary open-angle glaucoma (POAG), ocular hypertension (OHTN), and glaucoma treatment initiation in patients with type 2 diabetes mellitus (T2DM), compared to those initiating selective GLP-1 RAs.
DESIGN: Retrospective clinical cohort study using a nationwide electronic health records network from June 2022 to May 2025.
SUBJECTS: Adults with T2DM who initiated tirzepatide or selective GLP-1 RA therapy. Patients with prior exposure to either drug class, recent addition of second-line antihyperglycemic agents, previous glaucoma diagnosis or surgery, or ocular trauma were excluded.
METHODS: Data from 71 U.S. healthcare organizations were analyzed. Propensity score matching (1:1) was conducted to balance cohorts for demographics, comorbidities, medication use, and ophthalmic encounters. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each outcome.
MAIN OUTCOME MEASURES: Incidence of POAG, OHTN, and first-line glaucoma treatments (medications or surgery).
RESULTS: We identified 41,850 patients who initiated tirzepatide and 147,828 patients who initiated selective GLP-1 RAs. After matching, 41,849 patients remained in each cohort. Tirzepatide use was associated with a significantly lower risk of POAG (RR 0.50, 95% CI 0.34-0.74), OHTN (RR 0.59, 95% CI 0.40-0.88), and need for glaucoma treatment (RR 0.54, 95% CI 0.45-0.64) compared to selective GLP-1 RAs. Risk reductions persisted in subgroups with concomitant metformin or insulin use. Sensitivity analyses limited to patients aged ≥60 years and comparisons with individual GLP-1 RAs (semaglutide and dulaglutide) yielded consistent trends.
CONCLUSIONS: Tirzepatide use was associated with a significantly reduced risk of developing POAG, OHTN, and need for first-line glaucoma treatment compared to selective GLP-1 RAs in patients with T2DM. These findings suggest a potential additional ocular benefit of tirzepatide and support further investigation into its role in glaucoma management.
