Study details and key findings

Glucagon-like peptide-1 (GLP-1) drugs target areas of the brain that regulate appetite and food intake. One popular GLP-1 drug is semaglutide, which is available in two forms: Ozempic, a diabetes treatment, and Wegovy, a higher dose of the drug approved for weight loss.

For the study, researchers analyzed health insurance claim records for roughly 16 million U.S. patients, narrowing down their cohort to those with a recent history of obesity who had been prescribed a GLP-1 drug between 2006 and 2020. Patients with diabetes or who had been prescribed a diabetes drug were excluded since they already have an increased risk of certain stomach conditions.

In total, the researchers included data from over 5,400 patients. Of these patients, 613 had semaglutide prescriptions, and 4,144 had liraglutide prescriptions. Liraglutide is another GLP-1 drug that is sold under the brand name Saxenda when used for weight loss and Victoza when used for diabetes.

As a comparison, researchers also analyzed data from 654 patients with prescriptions for bupropion/naltrexone (Contrave), another weight-loss drug that works differently in the body.

Overall, the researchers found that while the incidence rate of serious stomach and intestinal issues among the three groups remained relatively low, those who were taking GLP-1 drugs had a significantly higher risk of developing these conditions than those who were taking bupropion/naltrexone.

Patients who were taking GLP-1 drugs were three times more likely to develop stomach paralysis and over nine times more likely to develop pancreatitis compared to those taking bubpropion-naltrexone. Patients on GLP-1 drugs were also over four times more likely to develop bowel obstructions, though this issue was only observed in patients taking liraglutide and bupropion/naltrexone and not semaglutide.

Although researchers also examined the risk of biliary disease among these patients, there were no significant differences among the three groups.

The researchers also noted that since the study was observational, it can only show associations and not causation. Another limitation is that while all GLP-1 patients had a record of obesity without diabetes, it's not clear that the GLP-1 drugs were all used for weight loss.

Commentary

According to CNBC, this is the first large, population-level study that examines the risk of serious stomach conditions among non-diabetic patients taking GLP-1 drugs for weight loss. Previously, FDA had received reports from patients about experiencing stomach paralysis while on semaglutide.

Although the incidence rates of stomach paralysis and other serious stomach issues were relatively low among the study's patients, "the number just continues to climb when you blow it up to the population level," said Mohit Sodhi, one of the study's authors.

"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," Sodhi said. "It's rare, but that's still a lot of people."

According to the researchers, they hope the study will inform healthcare providers prescribing GLP-1 drugs to their patients about the potential drawbacks of the medications.

"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."

Novo Nordisk, which manufactures both semaglutide and liraglutide, said it stands behind the safety and efficacy of its GLP-1 medications when they're used in a way that's consistent with product labeling and approved indications.

"With respect to the study, as the authors acknowledge, the study has limitations, including potential confounding by indication and by other factors," Novo Nordisk said. "We recommend patients take these medications for their approved indications and under the supervision of a healthcare professional. 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." (Twenter, Becker's Hospital Review, 10/5; Goodman, CNN, 10/5; Constantino, CNBC, 10/5; Sodhi et al., JAMA, 10/5)

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