Glucagon-Like Peptide-1 Analogs Associated with a Reduced Risk of Legal Blindness in Type 2 Diabetics with Cardiovascular Risks

Purpose: To evaluate whether glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy influences the risk of legal blindness and ischemic optic neuropathy (ION) among patients with type 2 diabetes mellitus (T2DM) and cardiovascular risk factors (CVRF). Design: A retrospective cohort study using de-identified electronic medical record (EMR) data from TriNetX, encompassing 72 healthcare organizations across the United States between January 2018 and January 2025. Participants: Adults (≥ 18 years) with T2DM (A1c < 10%) and at least one CVRF (hyperlipidemia, essential hypertension, overweight/obesity, or chronic ischemic heart disease) who were prescribed or not prescribed a GLP-1 RA. Methods: Patients with type 1 diabetes, optic neuritis, giant cell arteritis, or phosphodiesterase-5 inhibitor use were excluded. GLP-1 RA users were required to have ≥ 2 prescription records. A 1:1 propensity score matching (PSM) was performed to balance demographics, comorbidities, laboratory values, and concurrent antidiabetic medications. Outcomes were assessed at 1-, 3-, and 5-year follow-ups. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using univariable survival analyses. Main Outcome Measures: Incidence of legal blindness and ischemic optic neuropathy. Results: After PSM, each cohort included 350,536 patients (mean age 58.7 ± 12.6 years; 61.6% female). GLP-1 RA use was associated with a significantly reduced risk of legal blindness at 1 year (HR 0.589, 95% CI 0.476– 0.728), 3 years (HR 0.677, 95% CI 0.583– 0.788), and 5 years (HR 0.669, 95% CI 0.583– 0.768). There was no significant difference in ION incidence between cohorts at 1 year (HR 0.872, 95% CI 0.627– 1.212), 3 years (HR 1.002, 95% CI 0.792– 1.268), or 5 years (HR 0.978, 95% CI 0.789– 1.211). Conclusion: GLP-1 receptor agonist therapy was associated with a significantly lower risk of legal blindness and no difference in ION incidence. These findings indicate potential ocular benefits of GLP-1 RAs beyond glycemic and cardiovascular outcomes. Plain Language Summary: People living with type 2 diabetes have a higher risk of serious vision problems, including legal blindness and a condition called ischemic optic neuropathy, which occurs when the optic nerve does not get enough blood flow. New medications known as GLP-1 receptor agonists, originally developed to help manage blood sugar, have also been shown to improve cardiovascular health. Because circulation plays an important role in eye health, we wanted to understand whether these medicines might also influence the risk of major vision loss. We studied a large group of adults with type 2 diabetes and cardiovascular risk factors using medical records collected from clinics across the United States. We compared people who were taking GLP-1 medicines with those who were not. We followed both groups for up to five years to see how many developed legal blindness or ischemic optic neuropathy. We found that people taking GLP-1 medicines had a lower chance of developing legal blindness compared with those who were not taking these medications. We did not find a difference between groups in the number of people who developed ischemic optic neuropathy. These findings suggest that GLP-1 medicines may provide benefits for eye health in addition to their known effects on blood sugar and heart health. While our results are encouraging, future research—especially long-term studies that follow individuals over time—is needed to confirm whether GLP-1 medicines directly protect vision. Keywords: visual impairment, neuro-ophthalmology, retrospective study, ischemic optic neuropathy