A large retrospective study led by Johns Hopkins Medicine found that semaglutide and other GLP-1 receptor agonists are not associated with an increased or decreased risk of neovascular age-related macular degeneration NVAMD in adults with type 2 diabetes who had not previously used such…
A substantial new study led by researchers at Johns Hopkins Medicine has found no statistical link between the use of semaglutide and other glucagon-like peptide-1 receptor agonists GLP-1 RAs and the risk of developing a severe, blinding form of age-related macular degeneration in adults with type 2 diabetes. The findings help clarify a previously conflicting body of research about the eye-related effects of these widely prescribed medications.
An estimated 27 percent of U.S. adults with diabetes currently take GLP-1 RAs, drugs that mimic the GLP-1 hormone to lower blood sugar and promote weight loss. Some earlier studies had suggested these medications might alter the risk of developing other diseases, including age-related macular degeneration. The new work specifically examined neovascular age-related macular degeneration NVAMD , a fast-progressing condition caused by uncontrolled, abnormal blood vessel growth in the back of the eye that can lead to blindness.
The retrospective study, published online June 2 in the journal Ophthalmology, analyzed de-identified patient records collected from December 2017 through December 2024. The data came from 12 databases within the Observational Health Data Sciences and Informatics OHDSI network, an international collaborative of researchers and observational health databases.
Cindy Cai, M.D., the principal investigator and the Jonathan and Marcia Javitt Rising Professor of Ophthalmology at Johns Hopkins Medicine, explained that the study was designed to settle conflicting findings in the scientific literature. “Prior to our study, GLP-1s were reported to both increase and decrease the risk of developing AMD in the literature,” Cai said. “We wanted to resolve the lack of consensus with our work.”
The research team tracked health outcomes for adults with type 2 diabetes who had been prescribed one of six medications for the first time. The patient counts for each drug were: semaglutide, 227,971 individuals; dulaglutide, 68,588; exenatide, 5,460; empagliflozin, 252,356; sitagliptin, 100,083; and glipizide, 213,515. First-time users were defined as people who had no record of using GLP-1 RAs in their health files for at least 365 days and who started the medication only as a second-line treatment after metformin.
Cai noted that including multiple GLP-1 receptor agonists was deliberate. “We included other GLP-1 receptor agonists in our analysis to show our findings weren’t specific to a single drug,” she said.
Using both definitions, Cai’s team conducted two complementary analyses to calculate the rates of NVAMD onset among users of semaglutide and the other medications. The first approach was an active-comparator cohort analysis, which compared the risk of developing NVAMD between statistically matched groups of patients on each drug. This method allowed the researchers to assess whether people taking a particular medication were more or less likely to develop the eye condition compared to those on other treatments.
The second approach was a self-controlled case-series analysis, which focused only on patients who actually developed NVAMD. In this analysis, each patient served as their own control, and the researchers compared the incidence of NVAMD during periods when the patient was taking the medication versus periods when they were not.
In the active-comparator cohort analysis, the risk of developing NVAMD while taking semaglutide was found to be comparable to the risk associated with the other GLP-1 medications and also with the non-GLP-1 treatments empagliflozin, sitagliptin, and glipizide . None of the comparisons showed a statistically significant difference.
Results from the self-controlled case-series analysis were expressed as incidence-risk ratios. For semaglutide, the ratio was 1.02 when using the NVAMD-CP definition and 0.92 when using the NVAMD-C definition. A risk ratio of 1 indicates no difference in the likelihood of developing NVAMD while on the drug versus off the drug. Both ratios were so close to 1 that the differences could be attributed to random chance.
Overall, the researchers concluded that in both analytical frameworks, the risk of developing neovascular age-related macular degeneration while taking semaglutide or any of the other study medications did not differ enough to be considered statistically significant. The findings strongly suggest that GLP-1 RAs, including semaglutide, do not change the risk of this blinding eye disease in adults with type 2 diabetes who have no prior history of GLP-1 use.
Despite the clarity the study brings to earlier conflicting reports, Cai cautioned that the results should not be generalized to other patient populations. “Our study only looked at patients with existing type 2 diabetes who were prescribed semaglutide and other GLP-1 RAs,” she said. “But you don’t need a type 2 diabetes diagnosis to take these medications, so we can’t say if our findings hold true beyond this patient group.”
She specifically warned against applying the findings to people who take GLP-1 drugs primarily for weight loss, a growing demographic given the drugs’ popularity for obesity treatment. The study did not include individuals without type 2 diabetes, and Cai emphasized that additional research in that group is necessary.
The research article, edited by Gaby Clark and reviewed by Andrew Zinin, appeared in Ophthalmology. The full citation is: Cindy X. Cai et al., “Semaglutide and Neovascular Age-Related Macular Degeneration Among Adults with Type 2 Diabetes: An OHDSI Network Study,” Ophthalmology 2026 . DOI: 10.1016/j.ophtha.2026.05.034. The journal Ophthalmology is a peer-reviewed publication in the field.
The study was provided by Johns Hopkins University School of Medicine and covered key medical concepts including semaglutide, glucagon-like peptide-1 receptor agonists, and type 2 diabetes, with clinical relevance in ophthalmology, endocrinology, and clinical pharmacology.
Peptides referenced: Semaglutide, Exenatide, Dulaglutide, Glucagon, GLP-1.
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