Jury still out on effect of GLP-1 drugs on the eyes | AAO 2025

Two new abstracts released at the American Academy of Ophthalmology (AAO) showed mixed results about the impact of glucagon-like peptide 1 (GLP-1) drugs’ impact on the eye. The research summarized in one abstract showed GLP-1 drugs can increase the risk of diabetic retinopathy and nonarteritic anterior ischemic optic neuropathy (NAION), a condition that leads to loss of blood flow to the optic nerve. But the study summarized in the other abstract suggests that the drugs taken for weight loss and Type 2 diabetes may offer protection against dry age-related macular degeneration (AMD).

Clinical trials for GLP-1 therapies have found an association between GLP-1 drugs and diabetic eye complications, and the prescribing information for Ozempic/Wegovy (semaglutide) and Mounjaro/Zepbound (tirzepatide) includes warnings about diabetic retinopathy complications in patients with Type 2 diabetes.

Last year, a study was released that showed that GLP-1 drugs were associated with an increased risk of developing other ocular adverse events. The study assessed the FDA Adverse Event Reporting System and was published in January 2024 in Expert Opinion on Drug Safety. It found reported adverse events included blurred vision, visual impairment and diabetic retinopathy, with some adverse events occurring as early as 10 days after treatment initiation.

But another study, this one conducted by researchers at the Cleveland Clinic Cole Eye Institute in Ohio and published in the November/December 2024 issue of Ophthalmology Science, found that GLP-1 drugs do not lead to worsening of diabetic retinopathy. This study compared GLP-1 and sodium-glucose cotransporter 2 inhibitors (SGLT2is), a class of medications that help the kidneys to remove sugar.

Since then, researchers have been trying to understand the possible connection. In the first abstract at AAO, researchers at the University of Ottawa Eye Institute in Ontario, Canada, and the University of Toronto, along with McMaster University in Hamilton, Ontario, and the Doheny Eye Institute UCLA in California, conducted a study using data from the World Health Organization’s global database of drug safety reports. Researchers analyzed data on 117,173 patients with diabetes taking semaglutide, empagliflozin, exenatide, tirzepatide or insulin.

They found that people using semaglutide were 68.6 times more likely to develop NAION and eight times more likely to develop diabetic retinopathy than those taking empagliflozin, exenatide, insulin or metformin. The analysis found no significant association between tirzepatide and NAION or diabetic retinopathy.

But a separate abstract found that GLP-1 use was associated with a lower risk of developing one form of AMD compared with other glucose-lowering medications. Researchers at Cleveland Clinic Cole Eye Institute conducted a retrospective cohort study and assessed data from more than 430,000 patients 50 years or older with diabetes who took either GLP-1, SGLT2i, metformin or insulin for at least two years. All patients were seen at a single center, which allowed the authors to manually review all AMD cases identified by International Classification of Diseases, Tenth Revision coding.

The 7,319 patients taking a GLP-1 for five years showed a significantly lower risk of developing dry AMD, the most common form of the condition: 63% lower than for patients on metformin, 58% lower than for patients on insulin, and 54% lower than for those taking an SGLT2i.

The analysis showed no significant protection against the wet form of AMD, a rarer form of the disease where abnormal blood vessels cause fluid accumulation and bleeding in the macula.

Researchers of both studies suggest following guidelines issued last year by the AAO and the North American Neuro-Ophthalmology Society, which say that physicians and patients should discuss the individual’s overall health, risk factors and therapeutic options to make an informed decision about whether to continue or discontinue GLP-1 drugs.

“Patients deserve proactive care that includes documenting a baseline eye history, counseling on early visual symptoms, and streamlined referral pathways to ophthalmology so that emerging issues can be identified and managed without interrupting access to these therapies,” Moiz Lakhani, a medical student at the University of Ottawa, Faculty of Medicine, said in a news release.