Ocular Outcomes with Tirzepatide versus Glucagon-like Peptide-1 Receptor Agonists in Type 2 Diabetes.

OBJECTIVE

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown both protective and adverse effects on ocular outcomes. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA, achieves greater glycemic and cardiometabolic improvements than non-GIP agonistic GLP-1 RAs, 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-1 RAs.

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-1 RA, with no prior use of either drug class. Individuals who initiated any other second-line glucose-lowering therapies within 6 months before or during the study period were excluded to isolate the effect of the medication.

METHODS

A cohort of patients initiating therapy with tirzepatide was compared with another cohort initiating a non-GIP GLP-1 RA. 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 (VH)/retinal detachment (RD), need for vision-saving interventions (intravitreal injections, panretinal photocoagulation, or pars plana vitrectomy), and nonarteritic anterior ischemic optic neuropathy (NAION).

RESULTS

After matching, each cohort included 102 590 patients. Tirzepatide use was associated with decreased risk of DR (HR, 0.79; 95% confidence interval [CI], 0.72-0.87), DME (HR, 0.82; 95% CI, 0.68-0.96), VH/RD (HR, 066; 95% CI, 0.45-0.95), DR-related vision-saving interventions (HR, 0.65; 95% CI, 0.49-0.88), and NAION (HR, 0.45; 95% CI, 0.27-0.86) compared with non-GIP GLP-1 RA 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-1 RA, tirzepatide was associated with lower risks of retinal complications, need for vision-saving interventions, and NAION compared with GLP-1 RAs without GIP activity. These findings support a favorable ocular safety profile for tirzepatide, though confirmation in prospective studies is warranted.

FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.