Scientists involved in two large studies suggest their findings confirm that diabetes medication Ozempic doubles the risk of developing non-arteritic anterior ischaemic optic neuropathy (NAION), a rare but serious condition that damages the optic nerve.
Drawing on data from Danish and Norwegian health registers, they say the research validates earlier concerns raised in a smaller American study, and while the absolute risk remains low, they suggest the findings should guide discussions between doctors and patients about the benefits and risks of treatment with the drug.
However, Ozempic-maker Novo Nordisk said the studies did not demonstrate a causal relationship between semaglutide and NAION, while an expert who was not involved with the studies warned of the potential harm of scaring physicians or patients away from a medication which reduces the morbidity and mortality associated with T2DM.
Medical News Today reports that the teams, from the University of Southern Denmark, had conducted separate studies using different methods to analyse all Danish users of Ozempic.
Their new register-based studies corroborate, they wrote, a concern previously highlighted in the US research last year, which concluded that Ozempic more than doubles the risk of NAION.
In the first Danish study, the researchers analysed data from 424 152 Danes with type 2 diabetes and found that Ozempic doubles the chances of developing NAION.
The condition, caused by a sudden loss of blood flow to the optic nerve, can result in severe and permanent vision loss.
In the second Danish study, which is yet to be published in a peer-reviewed journal, the researchers categorised patients into two groups: those treated with Ozempic and those who received alternative treatments.
This study focused on a smaller, more specific group of patients with type 2 diabetes.
This research also revealed that the risk of developing NAION doubles for those taking Ozempic.
However, the researchers emphasised that their findings are not intended to discourage diabetes patients from continuing their treatment with Ozempic.
While untreated diabetes can cause various eye complications, these are generally less severe but more common than the optic nerve damage associated with NAION.
Lead author Prof Anton Pottegård, MSc Pharm, PhD, Dr Med from the Institute of Health Services Research, University of Southern Denmark, told Medical News Today: “The core finding is the simple fact that we see more cases of NAION, a very rare but serious disease of the optic nerve, among users of semaglutide than among users of other anti-diabetic medications. This finding is consistent across all of the analyses we’ve tried coming up with. While we don’t know why this happens, it seems the drug increases the risk of this disease.”
Novo Nordisk told MNT that “NAION is a very rare eye disease, and it is not an adverse drug reaction for the marketed formulations of semaglutide (Ozempic, Rybelsus and Wegovy) as per the approved labels”.
“After a thorough evaluation of the studies from the University of Southern Denmark and an internal safety assessment, Novo Nordisk is of the opinion that the benefit-risk profile of semaglutide remains unchanged,” a spokesperson said.
“While both studies showed a roughly doubling of relative risk, the absolute risk and absolute number of people affected is very low. This aligns with the low annual incidence of this rare disorder.
“One of the studies found that two people per 10 000 patients treated with semaglutide in a year developed NAION versus one out of every 10 000 in the comparator group, concluding that the absolute risk is very low. The studies did not demonstrate a causal relationship between semaglutide and NAION.”
What experts think
Three experts, who were not involved in these studies, spoke to Medical News Today. Benjamin Bert, MD, board certified ophthalmologist at MemorialCare Orange Coast Medical Centre in California, described the studies as “very interesting, as this is still a fairly new class of medication, having only been around for a few years”.
“Our knowledge of the full extent of the medication’s side effects is still being discovered.
“While this finding is concerning, especially given that there’s no treatment for NAION at this time, each individual’s risk and benefit of treatment with Ozempic needs to be discussed.”
Mark Anton, MD, medical director at Slimz Weightloss, agreed. “For patients, it’s crucial to balance the potential benefits of semaglutide with these risks.
“It emphasises the importance of regular monitoring and open communication with healthcare providers to tailor treatment plans to individual needs and risks.”
Howard Krauss, MD, surgical neuro-ophthalmologist and director of Pacific Neuroscience Institute’s Eye, Ear & Skull Base Centre in Santa Monica, said that type 2 Diabetes Mellitus (T2DM) is one of several risk factors in the occurrence of NAION and “one presumes that the influence of T2DM on the incidence of NAION may increase with the duration and severity of the disease”.
“But as the authors note, their study cannot claim a causal relationship,” he added.
Krauss also warned of the potential harm of scaring physicians or patients away from a medication which reduces the morbidity and mortality associated with T2DM.
This is because NAION is rare to begin with, and even with an increased incidence, it remains a rare condition.
Krauss highlighted the potential harm of the media publishing stories about rare side effects “leading to unfounded fear in the public mind”.
“A retrospective review of this nature should be published with editorial caveats to minimise public misperception. A report like this should lead to scientific testing of a hypothesis which may be proposed, that semaglutide may trigger NAION, but at this time it is nothing more than a hypothesis.”
Study details
Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes
Jakob Grauslund, Andreas Abou Taha, Lonny Stokholm et al
Published in International Journal of Retina and Vitreous on 18 December 2024.
Abstract
Background
Nonarteritic anterior ischaemic optic neuropathy (NAION) is an untreatable condition often causing severe and irreversible visual loss in the affected eye. As it has recently been implied that the use of semaglutide associates with NAION, the aim of the present study was to evaluate this risk prospectively in all persons with type 2 diabetes (T2D) in Denmark.
Methods
In a five-year longitudinal cohort study, we identified all persons with T2D in Denmark (n = 424,152) between 2018 and 2024. Patients were stratified according to exposure (n = 106,454) or non-exposure (n = 317,698) to once-weekly semaglutide, and incidence rates and hazard ratios (HR) of NAION were estimated in a multivariable Cox proportional hazard regression model.
Results
At baseline, median age and haemoglobin A1c were 65 years and 50 mmol/mol, and 54·5% were male. During 1,915,120 person-years of observation, 218 persons developed NAION. Semaglutide exposure was associated with a higher incidence rate (0·228 vs. 0·093 per 1000 person-years, p < 0·001) and independently predicted a higher risk of upcoming NAION (HR 2·19, 95% confidence interval 1·54 − 3·12), even when multiple other factors were taken into account. Overall, 67 persons exposed to semaglutide developed NAION with a median time from first prescription to event of 22·2 months (interquartile range 10·2–37·8 months).
Conclusions
During five years of observation of all persons with T2D in Denmark, use of once-weekly semaglutide independently more than doubled the risk of NAION. Given the irreversible nature of NAION, it is important to acknowledge this risk, and upcoming studies should aim to identify high-risk subgroups.
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