Tirzepatide Associated with Lower POAG, OHT Risk Compared with Other GLP-1 Drugs

Thus, the comparable tolerability of tirzepatide, despite its dual receptor activity, supports its feasibility for long-term use – an important consideration in managing chronic conditions like glaucoma. Photo: Eli Lilly. Click image to enlarge. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) 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 agonists alone. While GLP-1 drugs may offer neuroprotective effects relevant to glaucoma, the impact of dual-incretin therapies like tirzepatide on glaucoma remains unknown. Researchers from the University of Southern California and the University of California San Diego evaluated a large, nationally representative electronic health records database to determine the incidence of primary open-angle glaucoma (POAG), ocular hypertension (OHT) and first-line glaucoma interventions in patients with type 2 diabetes mellitus (DM) treated with tirzepatide vs. other GLP-1 RAs.They identified a significant association between tirzepatide use and both a lower risk of POAG and OHT, as well as initiation of glaucoma treatments in patients with type 2 diabetes, compared to those treated with selective GLP-1 drugs. These associations remained consistent across subgroup analyses, including patients using tirzepatide as adjunctive therapy to other first-line diabetes agents, among patients older than 60 and comparisons against individual GLP-1 drugs, including semaglutide and dulaglutide.The study, which was published in American Journal of Ophthalmology, analyzed data over about a three-year period from 71 US healthcare organizations of 41,850 patients who initiated tirzepatide and 147,828 patients who initiated selective GLP-1 drugs. After matching, 41,849 patients remained in each cohort. Compared to the GLP-1 cohort, the tirzepatide group was younger (mean age 55.1 years vs. 56.6 years), had a higher proportion of white patients (70.5% vs. 63.8%), lower rates of chronic kidney disease (10.3% vs. 13.5%) and insulin use (29.9% vs. 35.4%), higher body mass index (BMI; 38.1kg/m2 vs. 36.8kg/m2), and lower hemoglobin A1c (HbA1c; 7.3 vs. 7.6). Within the GLP-1 cohort, 76.4% were prescribed semaglutide, 18.1% dulaglutide, 5.1% liraglutide, 0.3% lixisenatide and 0.1% exenatide.Specifically, tirzepatide was associated with a 50% reduced risk of POAG, 26% reduced risk of OHT and 41% reduced risk of requiring new glaucoma treatment. Risk reductions persisted in subgroups with concomitant metformin or insulin use.“Our findings suggest that tirzepatide, through its dual GIP/GLP-1 action, may be superior as a non-IOP–lowering adjunct or even as a primary preventive agent in glaucoma management among patients with diabetes,” the researchers wrote in their paper.Rather than a drug-specific anomaly, they noted that these trends point to a broader therapeutic role for incretin-based therapies in ocular health, with tirzepatide potentially amplifying this benefit. Clarifying the mechanisms underlying these effects requires deeper exploration of tirzepatide’s distinct physiological actions beyond glucose control.Nevertheless, the team did emphasize that the short follow-up period in their study may be insufficient to fully capture the chronic trajectory of glaucoma development, particularly given the recent FDA approval of tirzepatide. As such, time-to-event analyses were not performed but may be considered in future studies with longer follow-up durations. Ultimately, causality cannot be inferred from these observational findings.Click here for the journal source. Hong AT, Lin F, Baxter S, Weinreb RN. Tirzepatide is associated with reduced risk of primary open-angle glaucoma and ocular hypertension in patients with type 2 diabetes. Am J Ophthalmol. December 5, 2025. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.