December 4, 2023

Medicines in the same class as Novo Nordisk’s popular weight-loss therapy Wegovy may carry an increased risk of pancreatitis, intestinal blockage and stomach paralysis compared to an older obesity drug, according to a study published on Thursday.

The study focused on two drugs from the class known as GLP-1 inhibitors, which help lower blood sugar levels for people with Type 2 diabetes: semaglutide is the active ingredient in Wegovy as well as Novo’s diabetes drugs Ozempic and Rybelsus; liraglutide is the active ingredient in the company’s earlier obesity medicine Saxenda and diabetes drug Victoza.

Nearly five in every 1,000 users of semaglutide drugs developed pancreatitis, compared to one of every 1,000 users of bupropion-naltrexone, the active ingredients in the weight-loss drug Contrave, according to a report in the JAMA medical journal. Contrave was approved in the U.S. in 2014 and in Canada in 2018.

For liraglutide, there were about eight cases of pancreatitis per 1,000 users.

Pancreatitis, or inflammation of the pancreas, can cause severe abdominal pain.

For stomach paralysis, researchers found roughly nine cases among every 1,000 users of semaglutide and about seven in liraglutide patients, compared with three among the same number of those taking bupropion-naltrexone.

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GLP-1 inhibitor medications mimic the actions of GLP-1, a natural hormone that helps control blood sugar levels in people with diabetes.

Mahyar Etminan, an epidemiologist at the University of British Columbia and senior author of the study, said up to two per cent of patients who used semaglutide and liraglutide medications to lose weight developed gastrointestinal problems.

“When you have millions of people taking them, that one per cent starts becoming a relatively big number,” he said. “One of my main concerns is that they’re long-term adverse events for which we really don’t have much data, especially for those who are taking them just for weight loss and not for diabetes.”

People with diabetes were not included in the study.

The study was observational, so it can only show associations, not whether the drugs caused the conditions. 

Weight management doctors in Canada, who’ve also done work for the drug companies, say the findings make sense.

“When we look at a medication that works at a much higher level and causes much more weight loss, we’re going to see more side-effects,” said Dr. Sean Wharton, an internal medical physician in Toronto.

Health Canada says it will review the new study along with others to determine whether safety warnings need to be updated. 

The results of this study are consistent with effects observed in clinical trials in obese patients, said Penny Ward, an independent pharmaceutical physician and visiting professor in pharmaceutical medicine at King’s College London in the U.K.

Ward told Science Media Centre that the study wasn’t designed to assess all possible side-effects of the treatments. 

“All of this information suggests that these agents should be used with care and only among patients at greatest risk of poor health or obesity-related complications that have been appropriately counselled about their risks,” Ward said.

G.I. warnings in U.S.

A Novo Nordisk spokesperson cited limitations of the study that might skew the results, including a failure to fully consider patients’ risk factors for gastrointestinal disorders.

The data also was collected between 2006 and 2020, before Wegovy was approved in the U.S. in 2021.

Novo Nordisk and Eli Lilly, whose GLP-1 diabetes drug Mounjaro is expected to be approved for weight loss this year, are facing several lawsuits in the U.S. accusing them of failing to warn users of the risks of severe stomach paralysis associated with the medicines.

GLP-1 drugs like Wegovy slow the passage of food through the stomach, helping people feel fuller longer. Problems can occur if stomach-emptying slows too much.

The U.S. Food and Drug Administration has recorded 209 incidents of Wegovy patients suffering from gastrointestinal disorders this year, 42 of whom were hospitalized.

Last month, the FDA updated the label for Ozempic to warn of the potential for intestinal blockage, which is already listed as a side-effect for Wegovy and Mounjaro.

The Institute for Safe Medication Practices Canada issued a bulletin last week after a patient who had been taking weekly semaglutide injections for weight loss vomited a large volume of undigested food while waking from anesthesia following orthopedic surgery.


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