While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used to treat both diabetes and obesity in patients, concerns around the ophthalmic safety of these medications continue to persist. In response to these continuing concerns, a Canadian team of researchers have conducted a large-scale, global pharmacovigilance study spanning 180 countries, to examine the previously documented associations between GLP-1 RAs and optic nerve and retinal adverse events (AEs). Published in the American Journal of Ophthalmology, the study analyzed data from the WHO’s VigiBase® and the US FAERS database (via OpenVigil 2.1) to look at accounts of retinal and optic nerve AEs associated with tirzepati and semaglutide, both widely used GLP-1 RAs.
“One of the most surprising findings was the dose-response effect we observed, where the longer patients were exposed to GLP-1 receptor agonists, the higher their relative risk of developing wet AMD,” notes study author, Reut Shor. “This was especially noteworthy given the increasing enthusiasm for these agents, driven by their well-established cardiovascular and metabolic benefits.”
The study underscores the importance of vigilance when it comes to evaluating new-onset vision loss in GLP-1 RA users. “For patients with early signs of AMD who are using or considering GLP-1 receptor agonists, ophthalmologists should communicate the potential risks,” warns Marko M. Popovic, study co-author. “While our study does not establish causation, the observed dose-dependent association warrants caution… Patients should be informed of this potential ocular risk, encouraged to report any new visual symptoms promptly, and advised on the importance of regular ophthalmic follow-up.”
The authors now call for prospective cohort studies, mechanistic research, and integration of ophthalmic endpoints into GLP-1 RA trials. Until more data emerge, shared decision-making and close collaboration between endocrinologists and ophthalmologists will be essential to balance risks and benefits. “While GLP-1 receptor agonists offer significant benefits in glycemic control, cardiovascular protection, and renal outcomes, our findings highlight the importance of considering potential ocular risks, particularly in high-risk individuals,” explains author Andrew Mihalache of the Temerty Faculty of Medicine, University of Toronto.
Rajeev H. Muni at the Department of Ophthalmology and Vision Sciences, University of Toronto, adds: “For long-term users, especially those who are older or have a history of stroke… clinicians may wish to exercise additional caution. Any new or changing visual symptoms in these patients should prompt a timely referral to an eye care professional.”
