- As the use of GLP-1 medications for weight loss continues to grow, researchers are examining how these drugs may affect other areas of our health.
- Previous studies have shown a potential link between GLP-1 use and non-arteritic anterior ischemic optic neuropathy (NAION), an eye condition that can cause vision loss.
- A new study found that Wegovy users may be at the highest risk of developing ION — an umbrella term for conditions including NAION — compared with users of other semaglutide-based GLP-1s.
- Scientists also found that this ION risk is almost three times higher in men than in women.
Researchers also found that this ION risk is almost three times higher in men than in women.
Scientists focused on alerts of ION associated with GLP-1 medications using semaglutide as their active ingredient:
- Ozempic for type 2 diabetes — weekly injectable dosages up to 2 mg
- Rybelsus for type 2 diabetes — one daily tablet
- Wegovy for obesity — weekly injectable dosages up to 2.4 mg
Of the more than 30 million unintentional and harmful side effects reported, about 32,000 involved semaglutide, with users having an average age of 56 and 54% female.
Of the incident reports involving semaglutide, about 3,000 were linked to Wegovy and originated in six countries across three continents, and almost 21,000 were attributed to Ozempic, with reports from 11 countries across four continents.
Upon analysis, researchers found that, despite a greater number of incident reports attributed to Ozempic, Wegovy was most strongly correlated with ION, exceeding the risk associated with both Ozempic and generic semaglutide.
Researchers noted that no ION incidents were reported in association with Rybelsus.
Additionally, scientists discovered that when looking at incident reports by gender, men on Wegovy had higher odds of experiencing ION-related complications.
At the end of the study, researchers found that the odds of developing ION were about 5 times higher among those on Wegovy than among those on Ozempic, and more than 3 times higher in men than in women.
As both Wegovy and Ozempic use semaglutide as their active ingredient, what might make Wegovy carry a greater ION risk?
Medical News Today spoke with Benjamin Bert, MD, a board certified ophthalmologist at MemorialCare Orange Coast Medical Center in Fountain Valley, CA — who was not involved in this study — to ask him this question.
“It was surprising to see the significant increase in risk of NAION with Wegovy compared to other GLP-1 medications, and especially Ozempic, since they have the same active ingredient,” Bert commented.
“The hypothesis of the authors of the study is that the increased risk of NAION with Wegovy is due to the higher dosage of semaglutide. In Wegovy, the semaglutide dosage is up to 2.4mg while Ozempic has a semaglutide dosage up to 2.0mg. The difference between the two dosages and the rates of NAION may indicate a dose dependent increase in risk of NAION.”
— Benjamin Bert, MD
“Future research should focus on this potential dose-dependent increase in adverse events with the GLP-1 medications,” Bert continued.
“As the authors discuss, there are other medications with different active ingredients and delivery systems (injection versus oral) that can help to modulate and reduce the risk of adverse events. Knowing how much GLP-1 agonist activity can be achieved before having adverse events, would help to titrate the dosages of the current medications and even the development of future medications in this class,” he added.
MNT also spoke with Dimitra Skondra, MD, PhD, the Terry and Mel Karmazin Professor of Ophthalmology and vice chair of research for the Department of Ophthalmology at NYU Grossman School of Medicine, about this study, who commented that while the findings highlight an association that deserves attention, they don’t establish causation.
“Patients who require GLP-1 medications often have underlying vascular and metabolic risk factors such as diabetes, obesity, and cardiovascular disease, which themselves increase the risk of ischemic optic neuropathy,” Skondra explained.
“Differences observed in retrospective analyses may therefore reflect these underlying risk profiles rather than a direct effect of the medication,” she pointed out.
“GLP-1 receptor agonists are being used by millions of patients worldwide, so it is important to continue evaluating potential systemic and ocular effects. At the same time, these medications have demonstrated substantial benefits in randomized clinical trials, including improvements in metabolic health and reductions in cardiovascular risk. Careful research is needed to distinguish true medication effects from associations driven by underlying patient risk factors.”
— Dimitra Skondra, MD, PhD
“We should take this signal seriously and work collaboratively across specialties to design well-controlled prospective studies that can more definitively answer whether there is a causal relationship,” Skondra said.
“Carefully designed prospective trials and mechanistic studies could help determine whether semaglutide affects optic nerve perfusion or whether the observed association reflects underlying patient risk factors,” she added.
