Elizabeth Wolkow, PharmD, New Ulm Medical Center
Background
Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) play a key role in treating diabetes and obesity. Long term ocular effects from prolonged exposure are still unknown. One leading cause of irreversible blindness worldwide is Age-Related Macular Degeneration (AMD). Neurovascular age-related macular degeneration (nAMD) is a severe form of AMD, leading to sudden and severe vision loss. Characterized by abnormal blood vessel growth, nAMD leads to damage of the macula causing loss of vision. GLP1-RAs reduce blood glucose levels through action on G-protein coupled receptors found in various tissues, including the retina.
Objective
Determine the risk of developing nAMD associated with use of GLP-1 RAs in diabetic patients.
Study Design
This was a retrospective cohort study conducted in Ontario, Canada from January 2020 to November 2023. Those included in the study were 66 years of age or older, had a diagnosis of diabetes, and had a minimum follow-up period of 12 months following an initial diagnosis. The treatment group of participants included those with diabetes and exposed to a GLP-1 RA for at least 6 months. The unexposed group of participants were patients with diabetes who never received a GLP-1 RA. Of the eligible patients that were identified, a 1:2 matched cohort was created. The primary outcome being evaluated was incidence and time to event of nAMD during the 3-year investigation period.
Results
After a 1:2 propensity score matching, a 1:2 matched cohort of 139,002 patients was created and divided into the two intervention groups. Of the 46,334 participants exposed to GLP-1 RAs, 93 individuals (0.2%) were newly diagnosed with nAMD. In contrast of the 92,668 participants who were not exposed to GLP-1 RAs, 88 individuals (0.1%) were newly diagnosed with nAMD. Cox proportional hazard models, both unadjusted (crude) and adjusted (for age, gender, duration of diabetes, comorbidities, and socioeconomic factors), estimated hazard ratios for nAMD development of greater than 2.0 among patients exposed to GLP-1 RAs (exposed, 0.2% vs unexposed, 0.1%; difference, 0.1%; crude: HR, 2.11; 95% CI, 1.58-2.82; adjusted: HR, 2.21; 95% CI, 1.65-2.96).
Conclusions
This large retrospective study revealed the use of GLP-1 RAs in individuals with diabetes was associated with a low but estimated 2-fold higher risk of nAMD development than those unexposed to GLP-1 RAs. These findings support the growing concern for potential ocular safety of GLP-1 RAs in patients with diabetes. Further research is needed to determine the true cause and effect of this relationship.
Published on November 17th, 2025.
References
- Shor R, Mihalache A, Noori A, et al. Glucagon-Like Peptide-1 Receptor Agonists and Risk of Neovascular Age-Related Macular Degeneration. JAMA Ophthalmol. 2025;143(7):587-594. doi:10.1001/jamaophthalmol.2025. 1455