A recent population-based cohort study has identified a significant association between the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and an increased risk of developing neovascular age-related macular degeneration (nAMD) among patients with diabetes.

The study, published this week in JAMA Ophthalmology, analyzed data from 139,002 patients aged 66 years or older in Ontario, Canada. Utilizing comprehensive administrative health and demographic data collected by the Institute for Clinical Evaluative Sciences, researchers led by Reut Shor, MD, of the University of Toronto created a matched cohort comprising 46,334 patients exposed to GLP-1RAs and 92,668 unexposed patients. Matching was based on factors such as age, gender, duration of diabetes, comorbidities, and socioeconomic status.

Over a follow-up period of 3 years, the incidence of nAMD was found to be 0.2% among the GLP-1RA-exposed group, compared to 0.1% in the unexposed cohort. Cox proportional hazard models indicated that GLP-1RA exposure was associated with a more than twofold increased risk of developing nAMD.

Most patients (97.5%) in the exposed group were prescribed semaglutide, with the remaining 2.5% receiving lixisenatide. The study did not differentiate between specific brands.

The authors of the study acknowledged that while the observational nature of the research precludes establishing causality, the findings warrant further investigation into the underlying mechanisms. They hypothesized that the rapid glycemic control achieved with GLP-1RAs might induce retinal hypoxia, promoting angiogenesis and contributing to nAMD development.

Given the increasing prescription of GLP-1RAs for both diabetes and obesity management, these findings underscore the need for heightened awareness among clinicians regarding potential ocular risks. Further research is essential to elucidate the pathophysiological mechanisms and to inform clinical guidelines for monitoring and managing patients on GLP-1RA therapy. RP