Todd Engel had operated heavy machinery, like forklifts and rubber-tire loaders, around warehouses and highways in suburban Maryland for four decades.

In early 2023, Engel's doctor put him on Ozempic, a GLP-1, for diabetes. That winter, on New Year's Eve, Engel woke up feeling as if a patch covered his right eye: "I couldn't see anything. It was all dark. It was black." The doctor told Engel and his wife Shelley it was a form of optic neuropathy — NAION, for short – an inoperable condition caused by tiny strokes that cut off blood flow to his eye. When the doctor listed all known causes, Shelley Engel specifically asked about Ozempic. "'We have heard nothing about that,'" she recalls the doctor telling her.

Seven months later, the journal JAMA Ophthalmology did publish research showing higher rates of NAION among diabetic patients taking Ozempic, or semaglutide, as the active ingredient name is known. But neither Engel nor his doctor were aware, so Engel kept taking weekly shots until his left eye went black, just as the other had done the year prior.

More than one in 10 Americans are taking a GLP-1 drug for weight loss, according to a recent Gallup analysis, and one in seven has taken them at some point. The drugs are prescribed for a growing number of conditions and come with a range of side effects.

Engel has filed a lawsuit alleging the maker of Ozempic, Novo Nordisk, failed to warn patients and doctors about the risk of NAION.

His suit is part of two main ongoing consolidated lawsuits alleging life-threatening or life-altering harm from GLP-1 drugs.

In a statement to NPR, spokespeople for Novo Nordisk pointed to subsequent research casting doubt on whether their GLP-1 drug causes NAION, for example, and said the cases are without merit.

The legal question before the courts hinges in part on whether the GLP-1 drugs caused the harm. Observational data can show correlation — that people taking GLP-1s were perhaps more likely to have this eye complication occur — but not causation. For that, more detailed investigation is needed.

When the JAMA Ophthalmology study came out showing the correlation between NAION and diabetic patients on Ozempic or semaglutide, two medical groups critiqued it. The American Academy of Ophthalmology and the North American Neuro-Ophthalmology Society issued their own consumer clarification saying, in part: "This is not the type of study that can show the treatment caused NAION." The groups did acknowledge there is a potential link, but further research would be necessary to determine that. For now, they don't recommend that patients stop taking their GLP-1s.

A partial database The Food and Drug Administration keeps a database tracking adverse events. It's one of the only mechanisms for doctors, patients and drug companies to submit reports of complications possibly linked to pharmaceuticals. Reporting is mostly voluntary and the agency does not verify the reports, but it is a crucial first step to prompt regulators to do further research and eventually decide, for example, if labels need updating.

In this database, NPR found more than 1,000 reports of optic neuropathy linked to GLP-1s since 2024. That's out of nearly 190,000 reports made about the drug over that period, most of which included minor gastrointestinal issues, dosing errors or injection site redness.

Spokespeople for Novo Nordisk — maker of Ozempic and Wegovy — say NAION and other serious conditions are exceedingly rare in clinical trials. The company continues to collect and share data with the FDA about the side effects reported with the drug since going to market, but the agency has not requested warning-label changes. The FDA said in an email to NPR it has undertaken its own study to assess NAION risks, and is assessing claims and will "determine the need for regulatory action" once its assessment is complete.

The legal challenge That is not sufficient for patients today, says attorney Jonathan Orent, a lead court-appointed attorney on the two major multi-district litigation lawsuits alleging harms from GLP-1 drugs. He says drug makers ought to update warnings to doctors and patients — as they have in Europe — even if the conditions are rare.

It's necessary, Orent says, because "you're never going to have the population size to detect rarer events in a clinical trial; you're also never going to have the diversity of your real world population."

Orent's cases include 247 plaintiffs with NAION, and more than 4,000 with other serious digestive conditions like pancreatitis or gall stones. "These warnings would have made a difference in the lives of real people," he argues. In an emailed statement, Eli Lilly, whose GLP-1 drug brands Mounjaro and Zepbound contain the active ingredient tirzepatide said it will "vigorously defend against these claims."

NPR's analysis of the FDA's adverse events data show 1,928 reports of pancreatitis since 2024. (Other forms of pancreatitis are also listed, including 135 cases of necrotizing pancreatitis.) Engel says he would've stopped taking Ozempic had he known that it might have put him at risk for blindness. Now, he mourns all he's lost, including the ability to work or walk the beach unaided. "Being able to play ball … with my grandchildren, I can't do these things anymore," he says. "I will never, never be able to see my wife's beautiful face every day." Uncertainty in reporting Obesity and diabetes are complex metabolic diseases that affect many organs, and increase risks for other ailments. That's part of what makes it hard to pinpoint whether problems that patients encounter on GLP-1 drugs are caused by the drugs themselves.

That's part of why Emory University diabetes specialist Mohammed Ali, for example, did not report any of the three patients he's treated who developed serious problems, like pancreatitis or gallstones, while taking GLP-1s, to the FDA's adverse events database.

He says he wasn't certain those problems were caused by the drugs themselves, even if the timing was suspicious.

"They may have had subclinical disease," Ali says. "In other words, we didn't know they had preexisting pancreatitis or preexisting gallstones." Calls to poison control The boom in online sales, where GLP-1s are heavily marketed, also adds to the challenge, says pharmacist Robert Miller at the West Texas Poison Control Center.

Buying drugs on Instagram? "That's definitely a new thing," Miller says, and many sites offer little to no medical supervision of patients. That's why, he says, more calls are coming into poison-control centers like his, with patients reporting vomiting or other GLP-1 side effects.

"So is there even a physician who's motivated to report side effects or someone the patient feels they can report those side effects to?" he says.

These questions are playing out now in court, where plaintiffs like the Engels are seeking damages from drugmakers.

But Shelley Engel also wants more side-effect warnings, which she says might've helped her husband avoid blindness. She says her husband's outgoing, vivacious personality has changed "This could have been prevented, if we only knew," she says.