Study Links Ozempic to Stomach Paralysis, Pancreatitis

Popular diabetes and weight loss drugs, such as Ozempic and Wegovy, may increase the risk of stomach paralysis and other severe gastrointestinal problems in non-diabetic patients, a study finds.

The medications, known as GLP-1 agonists, were originally developed for managing type 2 diabetes but have been increasingly used off-label for weight loss over the past decade. Wegovy and Saxenda, however, have been approved by the U.S. Food and Drug Administration (FDA) for weight management along with diet and physical activity.

The use of GLP-1 agonists was previously linked to vomiting and stomach paralysis, but evidence has remained anecdotal thus far. The first large, population-level study examining adverse gastrointestinal events in non-diabetic people who use these drugs for weight loss indicates that they indeed may elevate the risk of stomach paralysis, pancreatitis, and bowel obstruction. These side effects, however, are rare.

Researchers at the University of British Columbia (UBC) examined health insurance claim records for about 16 million American patients. They looked at people prescribed either semaglutide or liraglutide, two main GLP-1 agonists, between 2006 and 2020.

The study, published in JAMA, included only patients with a recent history of obesity who do not have diabetes or had not been prescribed another antidiabetic drug.

The researchers compared the rates of four gastrointestinal conditions among patients taking GLP-1 agonists for weight loss and those on bupropion-naltrexone, another weight loss medication.

The use of GLP-1 agonists was associated with:

• 9.09 times higher risk of pancreatitis, or inflammation of the pancreas, that can cause severe abdominal pain, fever, nausea, and vomiting. While most patients with acute pancreatitis recover quickly, about one in five cases can result in life-threatening complications, including multiple organ failure.
• 4.22 times higher risk of bowel obstruction, a blockage that prevents food from passing through the small or large intestine. The condition may cause cramping, bloating, nausea and vomiting. In severe cases, surgery may be required.
• 3.67 times higher risk of gastroparesis, or stomach paralysis, which limits the passage of food from the stomach to the small intestine. This may result in vomiting, nausea, and abdominal pain.

The study also associated GLP-1 agonists with an increased risk of biliary disease, a group of conditions affecting the gallbladder, but the difference was not statistically significant.

Patients should consider these severe, although rare, side effects when deciding whether to take GLP-1 agonists for weight loss, according to the study authors.

"The risk calculus will differ depending on whether a patient is using these drugs for diabetes, obesity, or just general weight loss. People who are otherwise healthy may be less willing to accept these potentially serious adverse events," said first author Mohit Sodhi, a graduate of UBC’s experimental medicine program and fourth-year UBC medical student, in a statement.

Authors note that as millions worldwide use the drugs, it could lead to hundreds of thousands of people experiencing severe gastrointestinal conditions.

"These drugs are becoming increasingly accessible, and it is concerning that, in some cases, people can simply go online and order these kinds of medications when they may not have a full understanding of what could potentially happen. This goes directly against the mantra of informed consent."

- Mohit Sodhi

The researchers hope that regulatory agencies and drug makers will consider updating the warning labels for their products by including the risk of stomach paralysis.

Effective, but risky?

GLP-1 agonists reached about 40 million prescriptions in the United States last year, while their global market is expected to grow to $100 billion by 2035.

Clinical trials demonstrate the high effectiveness of GLP-1 agonists, as they can help to lose between 10% and 15% of body weight when combined with lifestyle changes.

Moreover, the medications may have health benefits beyond managing blood glucose levels and weight reduction. A recent study linked Wegovy to a 20% lower risk of heart attack, stroke, or death from heart disease compared to placebo. GLP-1 agonists may also play a role in lowering dementia risk.

However, some side effects may not be well established yet. European Union and United Kingdom regulators are currently looking into reports that GLP-1 agonists may cause suicidal thoughts.

The new study that links novel medications for weight loss, such as Ozempic, to stomach paralysis and other serious gastrointestinal problems may encourage regulators to update warning labels for their products.