Highlights•GLP-1R agonists are linked with neuroprotection in neurodegenerative processes.•This study examined the effects of GLP-1R agonists on intraocular pressure (IOP).•GLP-1R agonist use was significantly associated with a small decrease in IOP.•Future prospective studies are needed to provide definitive insights.AbstractObjectiveThis study aims to provide data on the effects of glucagon-like peptide 1 receptor (GLP-1R) agonists on intraocular pressure (IOP).DesignRetrospective clinical cohort study.SettingMulticenter.Study Population1247 glaucoma surgery and treatment naïve eyes of 626 patients who were initiated on GLP-1R agonists compared to 1083 glaucoma surgery and treatment naïve eyes of 547 patients who were initiated on other oral antidiabetics.Observation ProceduresThe University of California Health Data Warehouse was queried for patients exposed to GLP-1R agonists or other oral antidiabetics. Index date was defined as the date of first exposure to the medication. Eyes with at least one pre-exposure and one post-exposure tonometry record within 365 days of the index date were included in the analysis. Clinical and laboratory data elements were extracted from the database. Eyes were censored from the analysis upon exposure to glaucoma hypotensive medication or glaucoma surgery. ∆IOP was analyzed using a paired t-test. Regression analysis was conducted using generalized estimating equations (GEE) accounting for inter-eye correlation. Sensitivity analyses were performed to assess the robustness of the findings.Main Outcome MeasuresPrimary outcome measure was ∆IOP after exposure to the medication.ResultsThe median age of all included subjects was 66.2 years [IQR=18.3]; 607 (51.7%) were female, and 667 (56.9%) were Caucasian. Median pre-exposure IOP, HbA1c, and BMI were 15.2 mmHg [IQR=3.8], 7.5 [IQR=2.4], and 29.8 [IQR=9.4], respectively. 776 individuals (66.1%) had diabetes, with the median number of active oral antidiabetics being 1.0 [IQR=1.0], and 441 (37.5%) being insulin users. Several pre-exposure characteristics significantly differed between the GLP-1R agonist and the control group. The mean ∆IOP was -0.4±2.8 mmHg (paired t-test p<0.001) and -0.2±3.3 mmHg (paired t-test p = 0.297) in the GLP-1R agonist and other antidiabetics groups, respectively. Pre-exposure IOP was the only independent predictor of ΔIOP in multivariable GEE. Sensitivity analyses yielded similar results.ConclusionsAlthough GLP-1R agonists were significantly associated with a decrease in IOP in the paired analysis, they were not associated with ΔIOP in multivariable GEE. Moreover, the difference between the ΔIOP in the two groups was small. Future prospective studies following a standardized dose and delivery method may provide further insights.

Association between Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists Exposure and Intraocular Pressure Change