GLP-1 Agonists, Like Ozempic and Wegovy, Have Risk of Gut Issues: Study

Pictured: Woman grasping her stomach in pain/iStock, Doucefleur

Pictured: Woman grasping her stomach in pain/iStock, Doucefleur

The use of glucagon-like peptide 1 (GLP-1) agonists for weight loss, such as Novo Nordisk’s Ozempic and Wegovy, is associated with the risk of gastrointestinal adverse events, according to a study published Thursday in the medical journal JAMA.

Specifically, the study found the class of drugs compared with bupropion-naltrexone were linked with an increased risk of pancreatitis, bowel obstruction, and gastroparesis but not biliary disease.

“Given the wide use of these drugs, these adverse events, although rare, must be considered by patients who are contemplating using the drugs for weight loss because the risk-benefit calculus for this group might differ from that of those who use them for diabetes,” the study’s authors wrote.

The authors said they examined gastrointestinal adverse events associated with GLP-1 agonists used for weight loss in a clinical setting because randomized trials evaluating their efficacy “were not designed to capture these events due to small sample sizes and short follow-up.” For their study, researchers used a random sample of 16 million patients taken between 2006 and 2020 from the PharMetrics Plus, a health claims database with 93% of all U.S. outpatient prescriptions and physician diagnoses. 

The study identified approximately 4,700 people who had been prescribed either semaglutide (Ozempic, Rybelsus and Wegovy) or liraglutide (Saxenda and Victoza)—focusing on those who took these drugs for weight loss, not diabetes, with a history of obesity and no diabetic diagnosis.

The class of drugs works by stimulating insulin production and reducing glucose production, which has made them a popular treatment for type 2 diabetes. However, the potential of these drugs in assisting with weight loss has caught the attention of patients as well as companies: many of the drugs approved only for diabetes are also prescribed off-label for weight loss. Wegovy was also approved for weight management by the FDA in June 2021.

Eli Lilly is the maker of diabetes drug Mounjaro (tirzepatide), a GIP/GLP-1 receptor agonist. The company is investigating tirzepatide in patients with overweight and obesity who do not have type 2 diabetes, with Mounjaro poised to add the hot indication of chronic weight management to its label by the end of this year.

The findings of Thursday’s JAMA study come as both Novo Nordisk and Lilly face legal challenges. They were sued in August 2023 by a Louisiana woman Jaclyn Bjorklund, who alleged the companies “downplayed the severity of the gastrointestinal events caused by Ozempic and Mounjaro,” and in particular played down the risk of gastroparesis, which is the slowing or stopping of the digestive system.

The suit alleges that she was hospitalized for stomach issues, including being sent to the emergency room, and suffered other adverse events such as losing teeth from excessive vomiting, throwing up whole food, and having to use other medications to alleviate her vomiting.

A Lilly spokesperson reportedly said the company’s “top priority” is patient safety, and that it “actively [engages] in monitoring, evaluating, and reporting safety information” for its medications.

The law firm that filed the lawsuit on Bjorklund’s behalf told CBS News it is investigating 400 other inquiries from clients across 45 states.

The American Society of Anesthesiologists recommended in June 2023 that patients stop taking GLP-1 agonists a week before elective surgeries, due to the increased risk of vomiting during surgery, while CNN reported in July other accounts of patients taking Ozempic and Wegovy suffering gastroparesis, with some claiming to have vomited days-old food.

Both medications note the risk of delayed gastric emptying, among other stomach problems such as nausea, vomiting, and diarrhea, but do not include an explicit warning of gastroparesis.

The drug class is also being investigated for possible suicidal ideation and self-harm risk by the U.K.’s Medicines and Healthcare products Regulatory Agency and the European Medicines Agency.

Connor Lynch is a freelance writer based in Ottawa, Canada. Reach him at lynchjourno@gmail.com.

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