Wegovy may have highest ischaemic optic neuropathy and sight loss risk

Wegovy, a GLP-1 agonist for weight loss, may carry the highest risk of ischaemic optic neuropathy (ION) and sudden sight loss of the semaglutide drugs, according to a study by researchers from the University of Ottawa, Ottawa, Ontario, Canada. They found that the risk is almost five times higher with Wegovy than it is with Ozempic, and three times greater in men than it is in women.

ION is caused by inadequate/interrupted blood flow to the optic nerve, resulting in sudden vision loss in one or both eyes. Although rare, ION has recently been linked to GLP-1 receptor agonists, particularly semaglutide, marketed as Wegovy, Ozempic, and Rybelsus, and variously used to treat obesity, diabetes, and to reduce cardiovascular disease risk, explain the researchers.

To pinpoint whether the risks of ION might be associated with particular drugs, the researchers analysed alerts of unintentional and harmful side effects associated with medicines submitted to the FDA Adverse Event Reporting System (FAERS) between December 2017 and December 2024.

The researchers focused on ION associated with up to 2 mg of weekly injectable Ozempic for type 2 diabetes; up to 2.4 mg of weekly injectable Wegovy for obesity, the highest approved dose, and a daily tablet of Rybelsus for type 2 diabetes. They also included a once-weekly injection of tirzepatide, a dual GLP-1/GIP agonist for the treatment of obesity and diabetes, which was analysed as a combined category and by indication: Mounjaro (for type 2 diabetes); Zepbound (for obesity).

Out of 30,668,520 unintentional and harmful side effect reports, 31,774 involved semaglutide; recipients had an average age of 56, and over half (54%) were female. Of these reports, 3070 were attributed to Wegovy, originating from six countries on three continents, and 20,608 to Ozempic, originating from 11 countries in four continents. Ozempic generated about seven times more reports than Wegovy owing to its earlier approval in 2017; Wegovy was launched in 2021.

Yet despite this difference in volume, Wegovy was most strongly associated with ION (28 reports; higher odds of nearly 75), exceeding Ozempic (47 reports; higher odds of nearly 19) and generic forms of semaglutide (85 reports; higher odds of 21).

ION was not reported in association with Rybelsus. And there was no signal, possible causal association between a medicine and an unintended side effect, with the comparator drugs.

When stratified by sex, the highest signal was for Wegovy in men (116 greater odds) and for Ozempic in women (nearly 27 greater odds). Further analysis indicated that the odds of ION were nearly five times higher with Wegovy than with Ozempic, and more than three times higher in men than in women.

Injectables are faster acting than tablets, and differences in route, dose, and indication "may influence prescribing patterns and safety signals, with high-dose Wegovy probably driving the stronger association by predisposing to optic nerve hypoperfusion [low blood supply] through intravascular volume contraction, hypotension [low blood pressure] with nocturnal dips and autonomic instability, although no direct clinical link has been established," point out the researchers. "In contrast, the limited absorption and slower uptake of Rybelsus probably explain the absence of a detectable signal."

Media attention may have influenced reporting for Wegovy, they suggest, emphasising that the FDA reporting system precluded the ability to determine true incidence or assess whether reports clustered following regulatory recognition. And there was no information on co-existing conditions or disease severity either.

Nevertheless, "This study provides the first evidence of a formulation-and dose-dependent ION risk, with the strongest association observed for Wegovy," conclude the researchers. "These findings highlight a potential dose-dependent safety concern that warrants urgent prospective evaluation to guide prescribing and regulatory policy."

The findings were reported in the paper, ‘Ischemic optic neuropathy with semaglutide: global observational analysis of sex- and formulation- specific risk’, published in the British Journal of Ophthalmology. To access this paper, please click here