An estimated 27% of U.S. adults with diabetes use glucagon-like peptide-1 receptor agonists (GLP-1 RAs), a type of drug that mimics the GLP-1 hormone, to lower blood sugar levels and support weight loss. Some studies suggest that their use may reduce the risk of developing other diseases.
A new federally funded retrospective study led by Johns Hopkins School of Medicine strongly suggests that semaglutide and other GLP-1 RAs did not statistically change the risk of developing neovascular age-related macular degeneration (NVAMD), a rapidly progressive blinding condition caused by uncontrolled abnormal blood vessel growth in the back of the eye, in adults with type 2 diabetes and no prior GLP-1 use.
The peer-reviewed study, funded by the National Institutes of Health, was published online June 2. ophthalmology.
Cindy Cai, M.D., principal investigator and Jonathan and Marcia Javitt Emerging Professor of Ophthalmology at Johns Hopkins School of Medicine, says the study was designed to resolve existing conflicting research on the possible link between GLP-1 RA and age-related macular degeneration.
Prior to our study, GLP-1 was reported in the literature to increase and decrease the risk of developing AMD. We wanted to resolve the lack of consensus on our work. ”
Cindy Cai, MD, Principal Investigator, Jonathan Javitt and Marcia Javitt, New Professor of Ophthalmology, Johns Hopkins School of Medicine
Researchers analyzed de-identified patient data collected from December 2017 to December 2024 across 12 databases managed by the Observational Health Data Science and Informatics (OHDSI) Network, an international, interdisciplinary collaboration of researchers and observational health databases, and found that semaglutide (227,971 people), dulaglutide (68,588 people), exenatide (5,460), empagliflozin (252,356), sitagliptin (100,083), or glipizide (213,515) for the first time. First-time users were defined as individuals who did not have a GLP-1 RA listed in their health record for at least 365 days and initiated the medication only as second-line treatment to metformin.
“We included other GLP-1 receptor agonists in the analysis to show that our findings are not specific to a single drug,” Cai says.
People who developed neovascular AMD were identified based on specific medical codes present in their database profile. To ensure that no cases were missed, two researcher-designed definitions of the disease were used. 1) condition-treated NVAMD (NVAMD-CP) and 2) condition-only NVAMD (NVAMD-C). The original definition required medical codes for both NVAMD and NVAMD treatment in medical profiles applicable to this condition. The second definition requires only an NVAMD diagnosis code for a patient to qualify.
Using both NVAMD definitions, Cai’s team performed two sets of analyzes to calculate the incidence of neovascular age-related macular degeneration with semaglutide and other drugs: an active comparator cohort analysis and a self-controlled case series analysis.
In an active comparator cohort analysis, researchers compared the risk of developing neovascular age-related macular degeneration among statistically similar patients taking each drug to see whether they were more or less likely to develop NVAMD. They found that the risk of developing neovascular age-related macular degeneration while taking semaglutide was similar to other GLP-1 and non-GLP-1 treatments.
In the self-controlled case series analysis, the researchers studied only patients who developed neovascular age-related macular degeneration. Cai’s team determined that the incident risk ratio for semaglutide (the chance of developing NVAMD while on treatment versus the chance of developing NVAMD while off the drug) was 1.02 using the NVAMD-CP definition and 0.92 using the NVAMD-C definition. A risk ratio of 1 indicates no difference between the two groups.
Overall, in both analyses, the researchers concluded that the risk of developing neovascular age-related macular degeneration while taking semaglutide or other investigational drugs for type 2 diabetes was not different enough to be considered greater or less than chance.
Although the study reveals some conflicting findings about NVAMD risk in adults with type 2 diabetes and taking GLP-1 drugs, Cai cautioned that her group’s findings should not be extended to other groups, such as those taking GLP-1 drugs primarily for weight loss, and that additional studies should be conducted in people without type 2 diabetes.
“Our study included only patients with pre-existing type 2 diabetes who were prescribed semaglutide and other GLP-1 RAs,” she says. “However, a diagnosis of type 2 diabetes is not required to take these drugs, so we cannot say whether our findings apply beyond this patient group.”
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Reference magazines:
Kai, CX, others. (2026). Semaglutide and neovascular age-related macular degeneration in adults with type 2 diabetes: an OHDSI network study. ophthalmology. DOI: 10.1016/j.optha.2026.05.034. https://www.sciencedirect.com/science/article/pii/S0161642026003829
