A recent study published in the American Journal of Ophthalmology evaluated the association between tirzepatide initiation and the risk of primary open-angle glaucoma (POAG), ocular hypertension (OHT), and glaucoma treatment initiation in patients with type 2 diabetes mellitus (T2DM).
Give me some background.
Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) that has shown superior efficacy in glycemic control, weight loss, and cardiometabolic outcomes compared to GLP-1 RAs alone.
And despite previous studies indicating that GLP-1 RAs potentially provide neuroprotective effects in glaucoma patients, the impact of dual-incretin therapies—such as tirzepatide—on glaucoma remains unclear.
Let’s get into the study.
In this retrospective clinical cohort study, investigators identified T2DM patients using tirzepatide using the U.S. Collaborative Network within the TriNetX platform (which included 71 U.S. healthcare organizations) from June 2022 to May 2025.
- Why: To compare the risk of POAG, OHT, and glaucoma treatment initiation in T2DM patients on tirzepatide to those using selective GLP-1 RAs.
The setup: Propensity score matching (PSM, 1:1) was conducted to balance the cohorts for demographics, comorbidities, medication use, and ophthalmic encounters.
- Exclusion criteria: Patients with prior exposure to either drug class, recent addition of second-line antihyperglycemic agents, previous glaucoma diagnosis or surgery, or ocular trauma.
Tell me more about the cohorts.
The researchers identified 41,850 individuals who initiated tirzepatide and 147,828 patients who initiated selective GLP-1 RAs, and—after PSM—41,849 patients remained in each cohort.
Compared to the selective GLP-1 RA users, 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%)
- Decreased insulin use (29.9% vs. 35.4%)
- Higher body mass index (BMI, 38.1 kg/m2 vs. 36.8 kg/m2)
- Lower hemoglobin A1c (HbA1c, 7.3 vs 7.6)
In the GLP-1 RA cohort, the breakdown of agents used was as follows:
- Semaglutide: 76.4%
- Dulaglutide: 18.1%
- Liraglutide: 5.1%
- Lixisenatide: 0.3%
- Exenatide: 0.1%
And the findings?
Compared to selective GLP-1 RAs, tirzepatide use was associated with a significantly lower risk of:
- POAG (risk ratio [RR]: 0.50, 95% confidence interval [CI]: 0.34-0.74)
- OHTN (RR: 0.59, 95% CI: 0.40-0.88)
- Need for glaucoma treatment (RR: 0.54, 95% CI: 0.45-0.64)
Note: These risk reductions persisted in subgroups with concomitant metformin or insulin use.
Moreover: Sensitivity analyses limited to patients aged ≥60 years and comparison with individual GLP-1 RAs (i.e., semaglutide and dulaglutide) yielded consistent results.
Expert opinion?
“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 study authors explained.
The consistent trends in lowered risk of glaucoma and glaucoma treatment suggested a broader therapeutic role for incretin-based therapies in ocular health management, with tirzepatide potentially amplifying this benefit.
However: Further research is required to elucidate the physiological mechanisms underlying these effects beyond glucose control.
Any limitations?
The study authors highlighted two key issues:
- The observational study design prevented causality being inferred from this analysis
- The short follow-up period in the study may insufficiently capture the chronic trajectory of glaucoma development—especially considering the recent FDA approval of tirzepatide
Take home.
These findings demonstrate that tirzepatide use was associated with a significantly reduced risk of developing POAG, OHTN, and requiring first-line glaucoma treatment compared to selective GLP-1 RAs in T2DM patients.
Further: Tirzepatide may confer additional ocular benefits, with the study authors advocating for further investigation into its role in glaucoma management.