Association of Tirzepatide versus Glucagon-Like Peptide-1 Receptor Agonists with Incident Glaucoma in Patients with Type 2 Diabetes: A Retrospective Cohort Study

Objective: To assess the comparative risk of glaucoma among patients with type 2 diabetes mellitus (T2DM) treated with tirzepatide versus glucagon-like peptide-1 receptor agonists (GLP-1RAs). Design: A retrospective cohort study using data from a large, multinational, deidentified database. Participants: Adults aged ≥60 years with T2DM who were newly prescribed tirzepatide or GLP-1RAs during 2022-2024 across 21 countries were included. Individuals with a prior diagnosis of glaucoma, previous use of glaucoma medications, or cross-use of tirzepatide and GLP-1RAs during follow-up were excluded. Methods: Based on medication exposure, participants were divided into the tirzepatide and GLP-1RA groups. The 2 groups were balanced using 1:1 propensity score matching based on age, sex, race, smoking history, glycated hemoglobin, body mass index, prior use of glucose-lowering medications, corticosteroids, and comorbidities. Main Outcome Measures: Incident primary open-angle glaucoma (POAG) across a 2-year follow-up period. Results: A total of 51 540 participants were included in the final analysis. Tirzepatide, compared to GLP-1RAs, was associated with a lower risk of POAG after 2 years (hazard ratio, 0.65; 95% confidence interval, 0.44-0.96) of follow-up. This association remained consistent across multiple sensitivity analyses, including the exclusion of individuals with early POAG events after the index date, restricting the cohort to patients with ≥1 subsequent prescription during follow-up, an intention-to-treat design, and limiting the analysis exclusively to individuals with an ophthalmology visit. Conclusions: Tirzepatide was associated with a lower risk of POAG compared to GLP-1RAs; however, further studies are needed to confirm its clinical significance given the limitations of the current study. Financial Disclosures: The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.