Glucagon-Like Peptide-1 Receptor Agonists and Risk of Neovascular Age-Related Macular Degeneration

Importance Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are extensively used in treating diabetes and obesity, yet little is known about the long-term ocular effects of systemic prolonged exposure. Objective To evaluate the risk of developing neovascular age-related macular degeneration (nAMD) associated with the use of GLP-1 RAs in patients with diabetes. Design, Setting, and Participants This population-based, retrospective cohort study was conducted from January 2020 to November 2023, with a follow-up period of 3 years. Data analysis was performed from August 2024 to October 2024. The investigators used comprehensive administrative health and demographic data from patients in Ontario, Canada, which were collected by the Institute for Clinical Evaluative Sciences in the context of a universal public health care system. Inclusion criteria were patients aged 66 years or older with a diagnosis of diabetes and a minimum follow-up period of 12 months following initial diabetes diagnosis. Patients with incomplete Ontario Health Insurance Plan or Ontario Drug Benefit data or patients exposed to GLP-1 RA for less than 6 months were excluded. Of 1 119 517 eligible patients, a 1:2 matched cohort of 139 002 patients was created, including 46 334 patients who were exposed to GLP-1 RAs and 92 668 unexposed matched patients. Systemic comorbidities that were associated with any kind of AMD and socioeconomic status were used to calculate propensity scores. Exposure GLP-1 RA use for 6 months or longer. Main Outcomes and Measures The primary outcome was the incidence and time to event of nAMD during the follow-up period. Results Among 139 002 matched patients, mean (SD) patient age was 66.2 (7.5) years, and 64 775 patients (46.6%) were women. The incidence of nAMD was higher among the exposed cohort than among the unexposed cohort. Cox proportional hazard models, both unadjusted (crude) and adjusted, 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 and Relevance In this cohort study, the use of GLP-1 RAs among patients with diabetes was associated with a 2-fold higher risk of incident nAMD development than among similar patients with diabetes who did not receive a GLP-1 RA. Further research is needed to elucidate the exact pathophysiological mechanisms involved and to understand the trade-offs between the benefits and risks of GLP-1 RAs.