| In June, EU regulators said that people with type 2 diabetes taking semaglutide, the active ingredient in Novo Nordisk’s Ozempic and Wegovy, are at risk of developing a rare eye condition that can cause vision loss. This could possibly affect as many as 1 in 10,000 people taking the medicine. The regulators confirmed earlier studies that showed diabetics who used Ozempic were more than twice as likely to be diagnosed with the condition, nonarteritic anterior ischemic optic neuropathy, an acute optic nerve injury. Now a Canadian study has shown that older people taking GLP-1 drugs for diabetes face twice the risk of developing a different eye disease: neovascular age-related macular degeneration. Why would a medicine that affects insulin have anything to do with the eye? A possible explanation, the Toronto-based authors of the study say, is that GLP-1s have both a direct and indirect effect on the retina. GLP-1s, which trigger a rapid drop in blood sugar, could indirectly affect the eye by “shocking” the retina after it had adapted to a state of high blood sugar. Any sudden change could throw off its metabolism and decrease oxygen to the area, a condition called hypoxia. The retina then signals for more blood vessel growth to supply oxygen, causing macular degeneration. But the more likely explanation, says ophthalmologist David Hunter at Boston Children’s Hospital, is that GLP-1s effectively “trick” the retina into thinking it’s oxygen-starved. The retina actually has GLP-1 receptors. When obesity drugs bind to them, those blocked receptors act as if they’re oxygen-deprived, triggering blood vessel growth and macular degeneration. This explains why other diabetes drugs that aren’t GLP-1s, like metformin, don’t have the same vision-impairing effect. “We think that the overall net effect of these drugs — combining the direct and the indirect effect — might be harmful based on what we saw in the study,” says Reut Shor, the lead researcher on the team. And while patients who were elderly and who had experienced a stroke in addition to having diabetes were already at risk of macular degeneration, the incidence of the disease was significantly higher when they took GLP-1s, according to the results of a regression analysis the researchers ran. Although the exact biological mechanism at work here remains murky, the researchers said that for some elderly diabetic patients, the benefits might outweigh the risks. “We don’t think that there’s enough yet to look for changing a label or to put a warning on the drug,” says study author Rajeev Muni. “It’s about education.” — Michelle Amponsah | 
