Kayce Zangaro couldn't stop throwing up.

She had been taking Ozempic for a few months, starting in June 2023, with the goal of losing weight. Symptom-free at first, she lost 30 pounds. But when she increased her dose, the nausea began — followed by nonstop vomiting.

The 31-year-old Carrick, Pa., resident tried anti-nausea medication, but it wasn't working. After about a week, she was treated at St. Clair Hospital's emergency department for dehydration and diagnosed with cyclic vomiting syndrome.

She would return to the ER multiple times. Scaling back to a lower dose didn't work. Zangaro quit Ozempic for good. She was later diagnosed with a damaged esophagus.

"It just wasn't worth it," she said in January.

While Zangaro is not pursuing legal action, her story is similar to those of hundreds of others who have joined a large lawsuit concerning the class of medications that Ozempic belongs to — known as glucagon-like-peptides, or GLP-1s, and initially used to treat Type 2 diabetes.

The suit names Novo Nordisk, which manufactures semaglutide (FDA-approved under the name Ozempic for diabetes and as Wegovy for weight management), as well as Eli Lilly, maker of tirzepatide (Mounjaro for diabetes, Zepbound for weight and sleep apnea).

While 1,800-plus plaintiffs await next steps as the case inches closer to trial, plenty of other patients and their physicians laud the medications as transformative.

The evidence and testimonials thus far represent the double-sided nature of the medications: potentially life-changing in ways both positive and negative.

The suit

Lawyers for the plaintiffs allege pharmaceutical companies did not provide adequate warning about the gastrointestinal risk for injury — and even downplayed that risk — while funneling millions into advertising.

"We think that every injury the plaintiffs (in the lawsuit) are experiencing is significant and serious," Jonathan Orent, an attorney with the Rhode Island-based MotleyRice law firm and a lead litigator in the case, said in February. "We believe that the labels put forward by the defendants were insufficient for doctors and regular people to understand the risk."

Sean Logue, lead litigator at Carnegie-based Logue Law, said in February he had 10 to 20 plaintiffs from Ohio, West Virginia and Pennsylvania, with several in Allegheny County. "I get at least a call a day about this," said Logue. "More likely than not, the (problem) is removal of the gallbladder."

On Wednesday, U.S. District Judge Karen Marston in Philadelphia is scheduled to hear arguments regarding the plaintiffs' diagnosis of gastroparesis, a condition that occurs when the stomach muscles become paralyzed and are ineffective at moving food through the digestive tract. This can lead to abdominal pain, nausea, vomiting and constipation, as well as nutritional deficiencies, dangerous dehydration and bowel obstruction.

Defendants Eli Lilly and Novo Nordisk have asserted that the drugs provide adequate warning but have not been tested in people with gastrointestinal disease — and that reports of gastroparesis may simply be evidence of the drugs working as intended to slow gastric emptying and lead to feelings of fullness.

The fact that for many, gastric symptoms resolve after stopping the drug is further evidence that what plaintiffs are experiencing is not true gastroparesis, which is chronic, they say.

"Patient safety is Lilly's top priority, and we actively engage in monitoring, evaluating and reporting safety information for all our medicines," said an Eli Lilly spokesperson in an email.

"Our labels have always warned that acute gallbladder disease is a risk of Mounjaro and Zepbound, but only a small number of patients have filed claims against Lilly alleging gallbladder surgery. The labels further explain that patients should contact their health care provider immediately for appropriate clinical follow-up if they experience symptoms of gallbladder problems, including abdominal pain, fever, jaundice, or clay-colored stools."

Novo Nordisk did not respond to requests for comment.

Plaintiff lawyers allege that hundreds, if not thousands, of gastroparesis cases are linked to the medications. Wednesday's hearing will decide whether plaintiffs will need a gastric motility test, which involves eating food with a radioactive tracer and watching it move through the digestive tract, or if a physician's diagnosis will suffice.

This decision will alter the course of the litigation: Hundreds of plaintiffs could be thrown out for lack of proof from the costly test.

The number of plaintiffs in the lawsuit has nearly doubled since September, when the last hearing was held. Orent anticipates more people will join the lawsuit by the time an official trial date is set.

Skyrocketing popularity

It's hard to overstate how common the GLP-1 class medications have become since the first — exenatide — was approved in 2005 to regulate glucose levels in people with Type 2 diabetes.

A 2024 Kaiser Family Foundation poll found one in eight adults reported using the drugs, and nearly a third of those surveyed had heard "a lot" about them. Public figures, including U.S. Sen. John Fetterman, D-Pa., tech and political figure Elon Musk and entertainment icon Oprah Winfrey have reported taking the meds.

And the uses keep expanding. Also FDA-approved for sleep apnea, they're being explored for treatment of fatty liver disease, addiction management and Alzheimer's disease.

Pharmaceutical companies have spent $1 billion to market diabetes and weight loss drugs, including the GLP-1 medications, according to an analytics report by Media Radar. An April 2 study published in the journal JAMA found American spending on these drugs increased 500% between 2018 and 2023, skyrocketing to $72 billion.

They've gained such appeal that pharmacies began prescribing compounded versions of the trademarked drugs to address a shortage, although the FDA ruled in late April that companies must stop selling compounded versions because the shortage had ended.

The Outsourcing Facilities Association has sued, calling the stoppage of compounded prescriptions "reckless" and "arbitrary." Emily Hilliard, deputy press secretary for the U.S. Department of Health and Human Services, said the agency does not comment on ongoing litigation.

'So deeply positive'

Sarah Shotland, a 43-year-old writer and professor living in Shadyside, began taking a compounded GLP-1 about two years ago after acquiring it from a telehealth provider.

Within days, Shotland said she felt like a different person. She had been dieting in some way since the age of 5 and suffered from bulimia on and off since age 11.

"The second day I started taking it, I went to a birthday dinner," she recalled. "It was probably the first time in my life where I was at a table of delicious, abundant food, and I felt a sense that I was enjoying the food and was satisfied."

Shotland's goal, she said, was not to lose weight continuously but to maintain a low dose of the medication to keep what she calls "food noise" at bay and free her from food obsessions and chronic calorie counting.

She did experience some expected side effects — nausea, food aversion, reflux — during the first couple of months, but the symptoms disappeared within two months.

"It's been so deeply positive for me," she said. "These are the first two years of my adult life I don't have an eating disorder."

Because of the FDA's recent decision on compounded GLP-1s, Shotland's prescription is at risk of being canceled.

GLP-1s and addiction

Before Shotland tried a GLP-1 drug, she experienced relief from bulimia when she started medication for opioid use disorder to treat drug craving. Surprised, she asked her doctor if there was a link.

"He said to me, 'That doesn't surprise me at all,'" she said. "'These medicines are targeting the same reward system that you get from all these compulsive behaviors.'"

That observation is consistent with research. Studies since at least 2017 have shown animals on GLP-1 drugs consume less alcohol and show reduced cravings, and a 2025 paper published in JAMA Psychiatry that tracked human participants with obesity and diabetes for eight years found that they had markedly lower risk of being hospitalized for alcohol use disorder after using GLP-1 drugs.

Laura Davisson, professor of medicine and director of medical weight management at the West Virginia University School of Medicine, said she is observing similar patterns in patients, some of whom have told her they're drinking less while on the medications.

Researchers don't know exactly how this works, but there's some evidence the drugs can cross the blood-brain barrier and modulate release of the brain chemical dopamine, which is involved in reward, reinforcement and craving.

But for Wayne Evron, physician with St. Clair Medical Endocrinology, this trend has been concerning. He said his team will get 100 calls a day asking to be put on semaglutide.

"They get addicted to these things," he said. "They need more and more. It's been a big problem for us ..."

Drug reps are at St. Clair once a week, said Dr. Evron. He doesn't talk to them, but they give out free samples.

"I hate to say it, but it's been a bane of my existence," he said. "It's incessant. We have signs in our office that say, please stop asking for GLP-1 drugs. But they still call."

A new frontier of weight management

GLP-1s have been around for two decades. But for treating weight loss, it's still a bit of a new frontier.

Many physicians have found patients like Shotland do very well, to the point the drug category is eclipsing the success of past options.

"These medications are very effective at decreasing blood sugar, probably the most potent drugs we have that lower blood sugar," said Dr. Evron. "I've seen people on insulin for years that, all of a sudden, they're off insulin. There's no question that they work."

For weight management, Dr. Evron has seen more ambivalent success. Some respond well, whereas others end up with debilitating symptoms.

"The weight loss seen from these medications is pretty profound, unlike anything we've ever had in terms of medical treatment," Dr. Davisson said. "Surgical treatment is really the only thing we've had that works this well in the past."

A 2021 clinical study funded by Novo Nordisk testing semaglutide for weight loss and published in the New England Journal of Medicine found an average 15% reduction in weight at 68 weeks compared to the control group and secondary benefits in cardiovascular health and blood pressure.

A later iteration of the semaglutide clinical trial found participants gained two-thirds of their weight back after stopping the drugs, and heart health improvements reverted back to baseline.

Scientists also haven't elucidated long-term effects past a few years.

Not 'a quick fix'

A handful of patients have received gallbladder removal surgery after taking these drugs, said Dr. Davisson, but she said there is not a definitive link to the medication.

The side effects she sees are mostly mild to moderate and GI-related. Nausea and constipation are most common, whereas vomiting is rare in her experience. Occasionally, she's seen patients have to stop the medicines.

The 2021 clinical study found that 10% of participants reported experiencing severe adverse outcomes from semaglutide, and 7% discontinued the trial, compared to 3.1% in the control group.

Specifically, 4.5% reported gastrointestinal disorders after taking semaglutide, and one person died.

"Some people have had unrelenting constipation, and it's not worth it for them to stay on," said Amy Crawford-Faucher, chair of primary care at Allegheny Health Network. "In my experience, it resolves after they stop the medication. Many more patients stop it because it's not effective."

Dr. Crawford-Faucher makes sure to have discussions with patients about potential long-term effects and encourages the whole-body approach to health, which includes optimizing diet, mental health and exercise.

"People don't understand this isn't a quick fix," said Zangaro. "If you're not going to change your lifestyle, there's no reason to go on it."

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