People using diabetes drugs such as Ozempic for weight loss are at higher risk of pancreatitis, bowel obstruction and stomach paralysis compared to those who use another medication approved specifically for obesity management, a University of British Columbia study suggests.

Researchers examined a random sample of health insurance claim records of 16 million patients in the United States between 2006 and 2020 for use of semaglutide drugs, the active ingredient in Ozempic and other medications, as well as liraglutide, in Victoza.

The study, published Thursday in the Journal of the American Medical Association (JAMA), excluded patients with diabetes. It compared gastrointestinal harms among people with a history of obesity taking either of the two different types of diabetes drugs with those using the weight-loss pill bupropion-naltrexone, sold under the brand name Contrave. It was approved in the United States in 2014 and in Canada four years later.

The study cohort included 4,144 patients on liraglutide, 613 who used semaglutide and 654 on bupropion-naltrexone.

Dr. Mahyar Etminan, an epidemiologist and senior author of the study, said researchers combined the semaglutides and liraglutides into one category of GLP-agonists, which mimic the actions of GLP-1, a natural hormone that helps control blood sugar levels in diabetes patients. It鈥檚 not known if one type of drug caused a greater health risk or if they could be similarly problematic, he added.

Compared to bupropion-naltrexone, GLP-1 agonists were associated with a nine times higher risk of pancreatitis, or inflammation of the pancreas, which can cause severe abdominal pain. They were also linked to more than four times the risk of bowel obstruction, which prevents food from passing through the small or large intestine, resulting in symptoms such as nausea and vomiting, the study found.

The drugs prescribed off-label to treat obesity were associated with nearly four times higher risk of gastroparesis, or stomach paralysis, which limits the passage of food to the small intestine and causes symptoms such as vomiting, nausea and abdominal pain.

The study also found a higher incidence of biliary disease, a group of conditions affecting the gallbladder, but the difference was not found to be statistically significant.

Etminan said that overall, up to two per cent of patients who used semaglutide and liraglutide medications to lose weight developed gastrointestinal problems.

鈥淲hen you have millions of people taking them, that one per cent starts becoming a relatively big number,鈥� he said. 鈥淥ne of my main concerns is that they鈥檙e long-term adverse events for which we really don鈥檛 have much data, especially for those who are taking them just for weight loss and not for diabetes.鈥�

Ozempic, a weekly injectable that comes in a pre-filled, multi-dose disposable pen, has been associated with an increased risk of gallbladder disease and pancreatitis. Nausea and vomiting are also known side-effects of the medication that was approved in the United States in 2017 for Type 2 diabetes, followed by its approval by Health Canada a year later. The drugs鈥� popularity has skyrocketed because in part, they slow down digestion and keep food in the stomach longer, making people feel full.

Previous studies have highlighted some risks in patients with diabetes, but Etminan said this is the first large, population-level study to examine harmful gastrointestinal effects in non-diabetic patients using the drugs to lose weight.

Last week, the U.S. Food and Drug Administration announced Ozempic鈥檚 warning label would be updated to say it may be linked to a life-threatening intestinal blockage. The condition, called ileus, can lead to reduced blood flow to organs.There is no warning about ileus on the Canadian monograph.

Health Canada should require warning labels to include the risk of gastroparesis so patients know the risks, Etminansaid.

The regulator issued a notice in April, and updated it in August, to say common side-effects of Ozempic may include nausea, vomiting, diarrhea, stomach pain and constipation.

Kate Hanna, spokeswoman for the Canadian arm of Novo Nordisk, which makes both Ozempic and Wegovy, said the gastrointestinal side-effects of GLP-1 agonists are well known.

鈥淔or semaglutide, the majority of (gastrointestinal) side effects are mild to moderate in severity and of short duration,鈥� she said.

鈥淲hile diabetes is a well-known risk factor, there are other risk factors that may increase the risk of gastroparesis,鈥� added Hanna, who said that includes obesity, being female and nervous system diseases including Parkinson鈥檚 disease or multiple sclerosis.

Mohit Sodhi, lead author of the study and a fourth-year UBCmedical student researching the adverse effects of commonly prescribed medications, said he had an emergency room patient who was vomiting up to 20 times a day.

鈥淭he only thing I noticed about him that could potentially explain this was that he had recently started Ozempic for weight loss,鈥� Sodhi said.

That reminded him of anecdotal reports of gastroparesis related to off-label weight loss drugs and got him interested in delving into heath risks others may be experiencing, he said of what sparked his interest in the study.

Sodhi said he鈥檚 concerned that an increasing number of diabetes drugs are being used off-label for weight loss, including Rybelsus, which Health Canada approved in 2020. It is similar to Ozempic but may be more appealing to some people because it comes in pill form so there is no need for a needle, he added.

Wegovy was approved in 2021 to manage obesity but is not yet available in Canada.

The same year, Health Canada also approved the daily injectable Saxenda, another GLP-1 agonist, which can be used by adolescents between the ages of 12 to 17 to treat obesity.