In their separate studies, Jakob Grauslund, Professor of Ophthalmology, and Anton Pottegård, Professor of Pharmaceuticals, have used two different methods to investigate all Danish users of Ozempic.
Both of the new register-based studies from SDU confirm a concern that was raised earlier this year in a smaller American study. In the American study, it was observed that Ozempic more than doubles the risk of the rare condition NAION (non-arteritic anterior ischemic optic neuropathy), which causes damage to the optic nerve of the eye.
Jakob Grauslund and his research colleagues have validated the hypothesis of the American study in Denmark, where the drug Ozempic is used by 106,454 patients in the treatment of type 2 diabetes.
– We have examined data from all 424,152 Danes with type 2 diabetes. We found that Ozempic more than doubles the risk of developing NAION. NAION is damage to the optic nerve of the eye caused by a sudden stop of blood flow to the optic nerve. It is a condition that can lead to severe and permanent loss of vision, says Jakob Grauslund, Professor of Ophthalmology at the Department of Clinical Research, SDU, and Department of Ophthalmology E, Odense University Hospital.
What is NAION?
NAION is damage to the optic nerve of the eye. It is an irreversible condition: it cannot be treated and it does not improve over time. NAION can cause severe and permanent vision loss.
NAION is a result of the blood supply to the optic nerve of the eye suddenly being cut off. The restricted or non-existent blood flow causes severe and incurable damage to the optic nerve, which most often results in the loss of visual acuity (sharp vision) or significant reduction in the field of vision.
The condition is often developed by patients who are at particular risk of cardiovascular disease. The risk factors are diabetes, high blood pressure and high cholesterol. Patients affected by the condition also tend to have some physical conditions in the eye, which can be the triggering factor.
– In the study, we found that the risk is doubled. At the same time, in the clinic we have noticed that since Ozempic came on the market in 2018, the number of NAION cases in Denmark has increased, explains Jakob Grauslund.
– Whereas we used to see between 60 and 70 cases of NAION per year, we are now seeing up to 150. In addition, we have noticed that the patients who come to hospital due to NAION are more often patients with type 2 diabetes.
In Jakob Grauslund’s study, the researchers divided the patients into two groups: those who were treated with Ozempic and those who received other treatment. In the statistical analyses, age, gender, blood sugar and a wide range of other conditions were also taken into account.
Treatment of type 2 diabetes
Food, exercise and medicine are factors that can be adjusted in the treatment of type 2 diabetes.
Medicinal treatment consists of tablets, such as the drug metformin, or injections, such as insulin or Ozempic.
Same findings with a different method
Anton Pottegård and his research group, who are experts on medicine use, have closely examined a smaller, but more specific, sample of the group of patients with type 2 diabetes. They have compared new users of Ozempic with users of another drug used in the treatment of diabetes who are at the same stage of the disease. This ensures a very even and direct comparison. And they have done this in both Denmark and Norway.
– In collaboration with the Norwegian Institute of Public Health, we have looked at all Danish and Norwegian diabetes patients who started treatment with Ozempic and compared them with people who started treatment with another medication. As was the case for Jakob Grauslund, we found that the risk of developing NAION doubles if you take Ozempic, explains Anton Pottegård, Professor of Pharmaceuticals at the Department of Public Health.
Risk is doubled
As with the American study, both studies from the University of Southern Denmark show that Ozempic increases the risk of developing NAION and that this applies to everyone with type 2 diabetes and not just to those patients who are already very ill.
– Fortunately, according to our study the number of people affected is lower than was found in the American study, but the number of cases of NAION among the people who are receiving Ozempic has still doubled, says Jakob Grauslund.
The higher number of cases in the American study may be due to the focus on a limited group of patients and because the American data have a number of limitations that are not applicable in the Scandinavian health registers.
What is Ozempic?
Ozempic is used to treat type 2 diabetes. The active ingredient in Ozempic is called semaglutide. Ozempic contains semaglutide, as do similar medicines, including Rybelsus, which is the tablet form of Ozempic, and Wegowy, which is used to treat obesity.
It has not been possible to carry out a formal analysis of Wegowy because it has only been on the market for a short time, and a certain length of observation time is necessary. However, Anton Pottegård explains that cases of NAION have also been seen among Wegowy users, although preliminary observations indicate that the risk is considerably lower.
– The American study proposes a hypothesis about a possible association, so it was important to investigate whether it could be confirmed in follow-up studies with better data sources – data sources such as those we have access to in the Nordic region, explains Anton Pottegård.
– These are the registers we have now used to confirm this suspicion.
Could lead to a change in treatment
Left untreated, diabetes can lead to other changes and complications in the eyes. Although these conditions are less severe than the damage caused to the optic nerve by NAION, they are much more common. It is therefore not the intention of Jakob Grauslund and Anton Pottegård to advise diabetes patients to stop their treatment.
– This is a serious but very rare side effect. Often, we only learn about this kind of thing after a new drug has been on the market for a few years, as is the case with Ozempic. It should be emphasised that it is neither more serious nor more common than the rare side effects of many other medicines that we continue to use. It is, so to speak, just a new piece of the puzzle of understanding how this drug works, explains Anton Pottegård.
– We hope that our results can be used by doctors and patients to discuss the pros and cons of treatment with Ozempic, adds Jakob Grauslund.
Kurt Højlund is a professor of diabetes at Steno Diabetes Center Odense, SDU and Odense University Hospital. He sees patients with type 2 diabetes every day and is responsible for choosing the best treatment for them. Kurt Højlund is among the group of authors behind one of the studies. He says:
– It is extremely important that type 2 diabetes is treated, but you have to consider whether the small increased risk of severe vision loss by using Ozempic means that you should instead use one of the other new drugs that protect against kidney and cardiovascular disease. This is commensurate with the new guidelines which came into force on 25 November. We cannot yet with certainty identify patients with a particularly high risk. However, treatment with Ozempic should be stopped if NAION is detected in one eye. The vast majority of patients can be confident in receiving treatment with Ozempic, as the absolute risk is so low, but some people may prefer an alternative treatment following consultation with their doctor.
Danish and international authorities have been informed of the findings. NAION as a potential side effect of semaglutid, the active ingredient in Ozempic, has been a focus for the authorities over the past six months. The new findings will be incorporated into their ongoing work.
About the studies
Jakob Grauslund: 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.
- In the study, the researchers examined all 424,152 Danes with type 2 diabetes, who were divided into two groups, of which 106,454 had been treated with Ozempic and 317,698 were treated with other medicines. In the statistical analyses, factors such as age, gender, blood sugar and systemic diseases were taken into account.
- The average annual number of first-time NAION cases in Denmark increased from 67.6 to 148.0 following the introduction of Ozempic in 2018. Averages were used because the precise number fluctuates slightly from year to year.
- Ozempic carries a 2.19 times higher relative risk of developing NAION. This means that if a patient with type 2 diabetes takes Ozempic, they are more than twice as likely to develop NAION as those who do not use Ozempic.
- The study has been accepted in the International Journal of Retina and Vitreous but is not yet accessible online. Read the accepted manuscript (PDF).
Anton Pottegård: Use of semaglutide and risk of non-arteritic anterior ischemic optic neuropathy: A Danish–Norwegian nationwide observational study.
- In the study, the researchers investigated the number of patients in Denmark and Norway who developed NAION after starting treatment with Ozempic after 2018 compared with people who started other new medicine for the treatment of diabetes. In this way, the researchers examined Denmark and Norway using the same method to determine whether they obtained the same results.
- Ozempic carries a 2.81 times greater relative risk of developing NAION. This means that if a patient with type 2 diabetes takes Ozempic, they have almost three times the risk of developing NAION compared with those who do not use Ozempic.
- The study is undergoing peer-review and is available as pre-print. Read the manuscript at medxriv.
Both Danish studies show that the risk of developing NAION for the individual patient receiving treatment with Ozempic is only 0.2 per thousand per year, which is fortunately significantly lower than in the American study. NAION is a relatively rare condition, and the extra risk is therefore low. The researchers estimate that for every 10,000 people treated in a year, between 1.5 and 2.5 extra cases will be seen.
