Semaglutide Use Tied to Slightly Increased nAMD Risk in Older Diabetic Patients: JAMA
Canada: A recent observational cohort study from Canada revealed that older diabetic patients taking GLP-1 receptor agonists-primarily semaglutide-had a small but increased risk of developing neovascular age-related macular degeneration (nAMD). The absolute risk remained low, at 0.2% over 3 years among users versus 0.1% in non-users, highlighting the need for further research on this drug class.
The study, published in JAMA Ophthalmology, was led by Reut Shor from the Department of Ophthalmology and Vision Sciences at the University of Toronto. It analyzed the long-term ocular safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), medications increasingly prescribed for managing diabetes and obesity. Despite their growing popularity, data on their prolonged impact on eye health have been limited.
To investigate this potential concern, the researchers conducted a retrospective cohort study involving 139,002 older adults with diabetes, drawn from administrative health databases in Ontario. The data, covering three years from January 2020 to November 2023, were sourced from the Institute for Clinical Evaluative Sciences. Patients included in the study were aged 66 years or older, had a diagnosis of diabetes, and had not been previously diagnosed with nAMD. The team matched 46,334 GLP-1 RA users to 92,668 non-users, ensuring comparable demographics and comorbidities using propensity score matching.
The primary objective was to assess the incidence and timing of new nAMD diagnoses among those exposed to GLP-1 RAs for at least six months.
The study revealed the following findings:
- Patients using GLP-1 receptor agonists had more than double the risk of developing neovascular age-related macular degeneration (nAMD) compared to non-users.
- The crude hazard ratio for nAMD development was 2.11.
- The adjusted hazard ratio remained high at 2.21.
- Despite the relative risk increase, the absolute difference in nAMD incidence was only 0.1%.
- These findings highlight potential safety concerns, especially for older individuals already at higher risk for age-related eye disorders.
- Although the number of new nAMD cases was small, the observed statistical association calls for further investigation.
“This study highlights a possible link between systemic GLP-1 RA use and retinal changes leading to nAMD. As these medications become more common in chronic disease management, their long-term effects on the eye must be better understood,” the authors noted.
The study authors also stressed the need for balanced clinical judgment. The benefits of GLP-1 RAs in glucose regulation and weight control are well-established, and abrupt discontinuation is not advised. However, clinicians may consider monitoring for early signs of retinal changes in high-risk patients, particularly older adults with a family history of macular degeneration.
The authors concluded, "While the increased risk of nAMD remains relatively low in absolute terms, the findings underscore the importance of vigilant, personalized care when prescribing GLP-1 RAs. Additional studies are needed to explore the biological mechanisms underlying this association and determine whether specific patient populations are more vulnerable to ocular side effects."
Reference:
Shor R, Mihalache A, Noori A, et al. Glucagon-Like Peptide-1 Receptor Agonists and Risk of Neovascular Age-Related Macular Degeneration. JAMA Ophthalmol. Published online June 05, 2025. doi:10.1001/jamaophthalmol.2025.1455
