BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown both protective and adverse effects on ocular outcomes. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RA, achieves greater glycemic and cardiometabolic improvements than non-GIP agonistic GLP-1RAs, yet its ocular safety profile remains poorly characterized.
PURPOSE: To compare the risk of retinal complications in patients with type 2 diabetes (T2D) treated with tirzepatide versus non-GIP GLP-1RAs.
DESIGN: A retrospective cohort study analyzed a nationwide electronic health records network from June 2022 to June 2025.
PARTICIPANTS: Adults with T2D initiating tirzepatide or a non-GIP GLP-1RA, with no prior use of either drug class. Individuals who initiated any other second-line glucose-lowering therapies within six months prior to or during the study period were excluded to isolate the effect of the medication.
METHODS: A cohort of patients initiating therapy with tirzepatide were compared to another cohort initiating a non-GIP GLP-1RA. Hazard ratios (HRs) for several ocular outcomes over a 36-month follow-up period were calculated, using propensity score-matched cohorts (1:1) to address confounding from demographics, comorbidities, and medication use. Similar analyses were performed among subpopulations of metformin- or insulin-users at cohort entry and among those who initiated additional antihyperglycemic therapy after index prescription.
MAIN OUTCOME MEASURES: Risk of diabetic retinopathy (DR), diabetic macular edema (DME), vitreous hemorrhage/retinal detachment (VH/RD), need for vision-saving interventions (intravitreal injections, panretinal photocoagulation, or pars plana vitrectomy), and non-arteritic anterior ischemic optic neuropathy (NAION).
RESULTS: After matching, each cohort included 102,590 patients. Tirzepatide use was associated with decreased risk of DR (HR 0.60, 95% confidence interval [CI] 0.54-0.65), DME (HR 0.63, 95% CI 0.52-0.74), VH/RD (HR 0.36, 95% CI 0.23-0.55), DR-related vision-saving interventions (HR 0.44, 95% CI 0.32-0.60), and NAION (HR 0.31, 95% CI 0.15-0.64) compared with non-GIP GLP-1RA use. Associations were consistent among metformin and insulin users and in those who initiated additional antihyperglycemic therapy during follow-up.
CONCLUSIONS: Among patients with T2D taking a GLP-1RA, tirzepatide was associated with lower risks of retinal complications, need for vision-saving interventions, and NAION compared to GLP-1RAs without GIP activity. These findings support a favorable ocular safety profile for tirzepatide, though confirmation in prospective studies is warranted.
