Exposure to glucagon-like peptide 1 receptor (GLP-1R) agonists reduces glaucoma risk

Abstract Importance Glucagon-like peptide-1 receptor (GLP-1R) agonists regulate blood glucose and are commonly used to treat Type II Diabetes Mellitus. Recent work has shown that treatment with the novel GLP-1R agonist, NLY01, decreased retinal neuroinflammation and glial activation to rescue retinal ganglion cells in an animal model of glaucoma. Objective In this study, we used an insurance claims database to examine whether GLP-1R agonist exposure impacts glaucoma risk. Design, Setting, and Participants A retrospective cohort of adult patients who initiated a new GLP-1R agonist (i.e., exenatide, liraglutide, albiglutide, dulaglutide, semaglutide, or lixisenatide) was 1:3 age, gender, race, active diabetes medication classes, and year of index date matched to a cohort of patients who initiated a different class of oral diabetic medication during their time in the database. Exclusion occurred for <2 years in the database, age <18 years old, no visit to an eyecare provider prior to the index date, a prior diagnosis of glaucoma, glaucoma suspect, or ocular hypertension, or prior glaucoma medication, procedure, or surgery. Diabetes severity was assessed using hemoglobin A1c and the Diabetes Complications Severity Index (DCSI), a validated metric based on six categories of diabetic complications. Inverse probability of treatment weighting (IPTW) was used within a multivariable Cox proportional hazard regression model to test the association between GLP-1R agonist exposure and the primary outcome. IPTW was derived from a propensity score model based on the DCSI, HbA1c, demographic factors and other systemic health conditions. Exposure Glucagon-like peptide 1 receptor agonist. Main Outcomes and Measures New diagnosis of primary open angle glaucoma, glaucoma suspect, or low tension glaucoma. Results Cohorts were comprised of 1,961 new users of GLP-1R agonists matched to 4,371 unexposed controls. After IPTW, age was the only covariate imbalanced (SMD >0.1) between cohorts. Ten new diagnoses of glaucoma (0.51%) were present in the GLP-1R agonist cohort compared to 58 (1.33%) in the unexposed controls. After adjustment, GLP-1R exposure conferred a reduced hazard of 0.54 (95%CI: 0.35-0.85, P =0.007), suggesting that GLP-1R agonists reduce the risk for glaucoma. Conclusions and Relevance GLP-1R agonist use was associated with a statistically significant hazard reduction for a new glaucoma diagnosis. Our findings support further investigations into the use of GLP-1R agonists in glaucoma prevention.