Two new studies suggest GLP-1 receptor agonists may slightly increase the risk of nonarteritic anterior ischemic optic neuropathy NAION , a rare eye condition causing vision loss. However, the absolute risk remains very low, with only a few extra cases per 10,000 patients. Experts advise not…
As glucagon-like peptide-1 GLP-1 agonists become more widely prescribed for type 2 diabetes and weight loss, researchers continue to investigate their potential side effects. Two new studies, both published in the Annals of Internal Medicine, address concerns about possible vision problems associated with these medications. The studies, one from the United States and one from Sweden, found that people using GLP-1 drugs may have a slightly higher chance of developing nonarteritic anterior ischemic optic neuropathy NAION , a rare eye condition that can lead to sudden, painless vision loss. However, the authors emphasize that the absolute risk of this event is extremely low, meaning it remains unlikely for the vast majority of patients.
Previous research had already linked GLP-1 use, particularly semaglutide the active ingredient in Ozempic and Wegovy , to potentially blinding eye conditions. Most studies point to an association with ischemic optic neuropathy ION , an uncommon condition where blood flow to the optic nerve is compromised, leading to vision loss. NAION, the most common form of optic neuropathy in adults over 50, has been specifically highlighted in connection with GLP-1 use, though the exact mechanism behind this link is not yet understood. The new studies add to this evidence base but provide nuance by clarifying the size of the risk.
Researchers from Rutgers University conducted a target trial emulation using healthcare data from a large U.S. database of insurance claims. The analysis focused on adults aged 18 to 65 with type 2 diabetes who had started glucose-lowering medication. The team compared individuals treated with GLP-1 receptor agonists against those taking other diabetes medications, such as SGLT-2 inhibitors or DPP-4 inhibitors.
According to Chintan Dave, PharmD, PhD, Associate Professor of Pharmacy and Epidemiology at the Rutgers Ernest Mario School of Pharmacy and Rutgers School of Public Health and lead author of the U.S. study, "We found that GLP-1 receptor agonist use was associated with a small increase in the 18-month risk of ischemic optic neuropathy compared with SGLT2 inhibitors and DPP-4 inhibitors." Dave added that the signal was concentrated among adults aged 50 to 65 years and men, who accounted for approximately 85% and 70% of events, respectively.
Over an 18-month period, that increase translated into about three to four additional cases per 10,000 patients treated with GLP-1 medications. Dave explained that this corresponds to approximately one additional case for every 3,333 or 2,778 patients treated, depending on the comparison group. Even among the higher-risk subgroups of older adults and men, the event remained rare.
The researchers stressed that while the condition is uncommon, it is clinically important because vision loss from NAION can happen suddenly and may be permanent. Dave emphasized that "Sudden, painless changes in vision, particularly dimming or blurring in one eye, loss of part of the visual field, or sudden vision loss, should prompt urgent, same-day evaluation by an ophthalmologist or emergency department." The study authors also noted that the findings should not change current prescribing practices, as the absolute risk is very low.
In a separate study, researchers from the Karolinska Institutet analyzed nationwide healthcare data from adults aged 35 to 84 years with type 2 diabetes in Sweden. The data covered the period from 2013 to 2024 and included more than 293,000 participants who had started either a GLP-1 drug or an SGLT-2 inhibitor.
After one year of follow-up, the risk of NAION was 0.04% among people taking a GLP-1 medication and 0.02% among those taking an SGLT-2 inhibitor. Although this represents a doubling of the relative risk, the adverse event remained very rare in both groups. Benjamin Bert, MD, a board-certified ophthalmologist at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, who was not involved in the study, commented on the findings. He told Medical News Today that "Patients and physicians should interpret these numbers as a demonstration that the risk of having NAION can increase with use of a GLP-1RA medication. The risk, however, is still quite low."
Bert pointed out that the relative risk shows a doubling of the chance of NAION in the GLP-1 group compared to the SGLT-2 group, which sounds dramatic. But when looking at absolute numbers, the increase is only 0.02%, which is quite low. In practical terms, that corresponds to roughly four cases per 10,000 people taking a GLP-1 drug over one year, compared with two cases per 10,000 people taking an SGLT-2 inhibitor.
The Swedish study authors caution that further research is needed to fully understand the association between GLP-1 use and NAION risk, particularly regarding the role of confounding variables. Bert added that in a large population study, there are likely many confounding variables, and those become even more challenging when studying a disease like NAION that is already rare. He noted that the overall results showed an increased risk of NAION due to GLP-1RA use, but it was a small increase and the authors felt it could be due to the confounding variables they uncovered.
The researchers of both studies caution that the findings should be interpreted carefully and should not change current prescribing practices. Because the studies were observational, they cannot prove that GLP-1 medications directly caused the increase in risk. The authors suggest that the apparent link may instead highlight underlying differences between those receiving GLP-1s and those taking other diabetes medications. For instance, people prescribed GLP-1s may have more advanced or a higher burden of cardiovascular risk factors, both of which are independently associated with optic nerve disease.
For most people, the study authors conclude that the proven benefits of GLP-1 drugs for those with type 2 diabetes, such as improvements in blood glucose control, weight loss, and reductions in cardiovascular and kidney disease risk, outweigh this potential safety signal. Dave categorically emphasized, "I would not recommend stopping a GLP-1 medication solely because of this study." He noted that these medications have substantial benefits for diabetes, cardiovascular disease, kidney disease, and weight management, and the potential excess risk identified in the study was very small.
Dave advised that patients who are older, male, or have preexisting ophthalmic conditions may wish to discuss their individual risk with their clinician, but the findings should promote awareness rather than alarm. Bert echoed this sentiment, saying, "It is important to be aware of the risks and side effects associated with any treatment. In this case, as we learn more about the medications, there will be more data available. This helps us to understand more about the possible side effects. Newer medications then can help to adjust their mechanism of action to lower those risks." He suggested that if there is a concern, patients may want to discuss with their doctor whether another GLP-1 medication could have a lower risk profile for causing NAION.
Both studies indicate that while GLP-1 use may be associated with a small increase in the risk of developing NAION, the condition remains very uncommon, and any potential increase in risk is likely to be small in absolute terms. The authors underscore the importance of continued monitoring as use of GLP-1 medications expands worldwide. They advise people taking diabetes medication to seek prompt medical attention if they experience sudden changes in vision, including painless vision loss or new blind spots.
Peptides referenced: Semaglutide, Glucagon, GLP-1.
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