Two independent studies from the University of Southern Denmark (SDU) show that patients with type 2 diabetes who are treated with the drug Ozempic have an increased risk of developing damage to the optic nerve of the eye, which can lead to severe and permanent loss of vision. Both studies are based on Danish registers and are the largest in the world.

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.

– 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.

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.

– 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.