Blockbuster and diabetes drugs like and may be associated with an increased risk of three rare, but severe, in non-diabetic patients, according to a released Thursday.
The study, published in the research journal JAMA, comes as 's Wegovy, Ozempic and similar treatments skyrocket in popularity in the U.S. for their ability to cause dramatic weight loss over time. But those drugs, known as GLP-1s, are also facing increased scrutiny after some patients reported experiencing and while taking them.
GLP-1s work by slowing digestion to suppress a person's appetite but can cause problems if that process slows down too much.
Researchers at the University of British Columbia said the conditions in the study include not named in the warning for those drugs: , which slows or completely stops the movement of food from the stomach to the intestine and can cause symptoms like persistent vomiting.
The study also notes an increased risk of bowel obstruction, a disorder where food is blocked from passing through the small or large intestine, and pancreatitis, which refers to pancreas inflammation. The for the drugs already include warnings about and of bowel obstruction.
The researchers specifically examined semaglutide – the active ingredient used in Wegovy and Ozempic – and another GLP-1 called liraglutide against another weight loss treatment called bupropion-naltrexone, which works differently to help patients lose weight. Wegovy is specifically approved for weight loss in the U.S., while Ozempic is only approved for diabetes.
Their research is the first large, population-level study to examine the risk of serious stomach conditions in non-diabetic patients specifically using GLP-1s for weight loss.
have highlighted the of those conditions in diabetic patients taking GLP-1s, according to the researchers. People with diabetes are also at increased risk of experiencing stomach paralysis and pancreatitis overall, even without the treatments.
"That's why we kind of wanted to take diabetes out of the equation," said Mohit Sodhi, one of the authors of the study. "In addition to the fact that millions of people around the world are using these drugs to help them lose weight."
A spokesperson for Novo Nordisk noted that some of the gastrointestinal side effects in the study are already included on the labels for its GLP-1s, adding that the company "stands behind the safety and efficacy of all of our GLP-1 medicines when used consistent with the product labeling and approved indications."
"We recommend patients take these medications for their approved indications and under the supervision of a healthcare professional," the spokesperson said. "Treatment decisions should be made together with a healthcare provider who can evaluate the appropriateness of using a GLP-1 based on assessment of a patient's individual medical profile."
The study findings are based on an analysis of health insurance claim records for roughly 16 million U.S. patients.
Researchers specifically looked at people with a recent history of obesity who were prescribed semaglutide or liraglutide between 2006 and 2020. They excluded those with diabetes or patients who had been prescribed another diabetes drug.
Most patients in the study were prescribed liraglutide, but researchers said the increased risks they observed could apply to the entire GLP-1 drug class.
"Our data end date was the end of 2020, while the recent boom in semaglutide happened in the last year," Sodhi said. "Nonetheless, we believe it is a class effect."
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The researchers measured the rate at which patients developed four different serious stomach conditions while taking semaglutide, liraglutide and bupropion-naltrexone, which are stomach paralysis, pancreatitis, bowel obstruction and biliary disease, a group of conditions affecting the gall bladder.
Compared with bupropion-naltrexone, GLP-1s were associated with a 9 times higher risk of pancreatitis, a 4 times higher risk of bowel obstruction and a more than 3 times higher risk of stomach paralysis, according to the study. The findings suggest the risks of those conditions are higher in patients specifically taking GLP-1s rather than other weight loss medications that work differently.
Around 7 out of every 1,000 patients experienced stomach paralysis while taking liraglutide, and nearly 10 out of every 1,000 patients experienced that condition while taking semaglutide.
And Sodhi noted, "the number just continues to climb when you blow it up to the population level."
"When you have more than a million people taking the medication worldwide, that's 10,000 people who could potentially experience gastroparesis according to the incidence rate for semaglutide," he told CNBC. "It's rare, but that's still a lot of people."
Almost 5 out of every 1,000 patients experienced pancreatitis while taking semaglutide, while roughly 8 out of every 1,000 patients experienced that condition while taking liraglutide.
Meanwhile, around 8 out of every 1,000 patients experienced bowel obstruction while taking either of those GLP-1s.
The researchers also found a high rate of biliary disease in patients taking either liraglutide or semaglutide, but they said the difference was "not found to be statistically significant."
The researchers hope the study will inform health-care providers prescribing GLP-1s about the potential drawbacks of taking the drugs.
"We're all big proponents for informed patient consent," Sodhi said. "If someone has decided they would like to take a GLP-1 for weight loss, we encourage them to have a conversation with their provider about how it may help them achieve their goals. But they should also be made aware of the potential drawbacks of taking this medication."
