While many have raved about the powers of popular weight-loss drugs like Wegovy and Ozempic, new research confirms the medications can trigger some nasty gastrointestinal side effects.

Known as GLP-1 agonists, they may increase the risk of stomach paralysis, pancreatitis and bowel obstruction, scientists found.

“Although the incidence of these adverse events are relatively rare, affecting only about 1% of patients, with millions taking these medications, thousands of people are likely to be affected by these adverse events,” said lead researcher Dr. Mohit Sodhi, from the University of British Columbia in Vancouver.

“Patients need to weigh the risks and benefits before taking these medications for weight loss,” he said. “We encourage patients who are interested in using these medications to have a lengthy conversation with their physician to see if this medication is appropriate for their goals and what they hope to achieve.”

GLP-1 agonists were originally developed to help manage type 2 diabetes by lowering blood sugar, but they also promote weight loss and have been used off-label for more than a decade. In 2021, some forms of these drugs were approved to treat obesity.

Most patients experience symptoms like constipation and nausea, so the possibility of these more serious side effects is not surprising, said Dr. Caroline Messer, an endocrinologist at Lenox Hill Hospital in New York City.

Still, “patients really shouldn’t be worrying about pancreatitis any more than vaguely worrying about pancreatitis anytime they were committed to losing an excessive amount of weight quickly,” she said.

“We’re all aware of all these side effects,” Messer said, but the benefit of losing 40 to 50 pounds clearly outweighs the small risk of these side effects.

“You decrease your risk of gout, heart disease, strokes, heart attacks and diabetes, so these risks in no way convince me to stop prescribing these medications,” Messer said.

For the study, Sodhi and his colleagues examined health insurance claims for approximately 16 million U.S. patients and looked at people prescribed GLP-1 agonists — either semaglutide (Ozempic) or liraglutide (Victoza) — between 2006 and 2020.

The investigators compared the risks of these drugs with another type of weight-loss drug called bupropion-naltrexone (Contrave).

Compared to bupropion-naltrexone, GLP-1 agonists were associated with:

  • Nine times higher risk of pancreatitis, or inflammation of the pancreas, which can cause severe stomach pain and, in some cases, require hospitalization and surgery.
  • Four times higher risk of bowel obstruction, where food is prevented from passing through the small or large intestine, resulting in cramping, bloating, nausea and vomiting. Depending on the severity, surgery may be required.
  • Four times higher risk of gastroparesis, or stomach paralysis, which limits the passage of food from the stomach to the small intestine and results in symptoms like vomiting, nausea and abdominal pain.
  • Researchers also found a higher risk for biliary disease, which affects the gallbladder, but this difference was not statistically significant.

The report was published online Oct. 5 in the Journal of the American Medical Association.

Dr. Jamie Kane, director of the Northwell Health Center for Weight Management in Great Neck, N.Y., said these risks are known and are rare, but patients need to be informed about them before they start one of these medications.

“We have to look at risk-benefit ratios and decide whether it makes sense to prescribe them,” Kane said. “It’ll come down to a discussion between physician and patient as to the risk of morbid obesity with chronic conditions and the lifestyle associated with that for pancreatitis and cancer and other disease processes and the slightly increased risk from the drug.”

Kane said that patients who shouldn’t be taking these drugs are those with a history of pancreatitis.

One expert stressed that while weight-loss drugs can be effective, the best way to maintain a healthy weight is with a healthy lifestyle.

“GLP-1 agonists appear to be highly effective drugs for both diabetes management and weight loss. But as with all drugs, there are potential side effects, and some of them are severe,” said Dr. David Katz, a specialist in preventive and lifestyle medicine and president of the True Health Initiative.

“We don’t yet have the long-term experience with these drugs to understand fully the risk/benefit trade-offs with extended use, but the adverse effects chronicled here are a precautionary tale,” he said.

This is a good reminder that the first, best and safest approach to managing weight and metabolic health is a healthy diet and lifestyle, Katz said.

“Interest in GLP-1s should not distract us from doing all we can to leverage food as medicine, and to ensure everyone’s access to a high-quality diet,” he said. “Drugs, with their attendant costs and inherent risks, should be a last resort.”

More information

For more on GLP-1 agonists, head to the Cleveland Clinic.

SOURCES: Mohit Sodhi, MD, University of British Columbia, Vancouver, Canada; Jamie Kane, MD, director, Northwell Health Center for Weight Management, Great Neck, N.Y.; Caroline Messer, MD, endocrinologist, Lenox Hill Hospital, New York City; David Katz, MD, MPH, specialist, preventive and lifestyle medicine, and president, True Health Initiative, Tulsa, Okla.; Journal of the American Medical Association, Oct. 5, 2023, online