HQ Team
October 7, 2023: Diabetes drugs used in weight-loss therapies may come with a risk of stomach paralysis, pancreatitis and bowel obstruction, a study by the University of British Columbia found.
The weight-loss medicines are known as GLP-1 agonists — which include brands like Wegovy, Ozempic, Rybelsus and Saxenda. They increase the probability of severe gastrointestinal complications.
“Given the wide use of these drugs, these adverse events, although rare, must be considered by patients thinking about using them for weight loss,” said first author Mohit Sodhi, a graduate of UBC’s experimental medicine program, and who studies the adverse events of commonly prescribed medications.
“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,” he said.
The study is the first large, population-level study to examine adverse gastrointestinal events in non-diabetic patients using the drugs specifically for weight loss, according to a University statement.
40 million prescriptions
GLP-1 agonists were originally developed for managing Type 2 diabetes, but gained popularity over the past decade as an off-label weight-loss tool, reaching approximately 40 million prescriptions in the US in 2022.
In 2021 some forms of medications were approved as a treatment for obesity. Randomized clinical trials examining the efficacy of the medications for weight loss were not designed to capture rare gastrointestinal events due to their small sample sizes and short follow-up periods.
The researchers examined health insurance claim records for about 16 million US patients and looked at people prescribed either semaglutide or liraglutide, two main GLP-1 agonists, between 2006 and 2020.
They included patients with a recent history of obesity, and excluded those with diabetes or who had been prescribed another anti-diabetic drug. They analysed the records to see how many patients developed one of four gastrointestinal conditions and compared that rate to patients using another weight-loss drug, bupropion-naltrexone.
Pancreatitis
Compared to bupropion-naltrexone, GLP-1 agonists were associated with a 9.09 times higher risk of pancreatitis, or inflammation of the pancreas, which can cause severe abdominal pain and, in some cases, require hospitalisation and surgery.
GLP-1 medications also had a 4.22 times higher sit of bowel obstruction — when food is prevented from passing through the small or large intestine, resulting in symptoms like cramping, bloating, nausea and vomiting. Depending on the severity, surgery may be required.
The agonists had a 3.67 times higher risk of gastroparesis, or stomach paralysis, which limits the passage of food from the stomach to the small intestine, resulting in symptoms like vomiting, nausea and abdominal pain.
“There have been anecdotal reports of some patients using these drugs for weight loss and then presenting with repeated episodes of nausea and vomiting secondary to a condition referred to as gastroparesis,” said senior author Dr. Mahyar Etminan, an epidemiologist and associate professor in the department of ophthalmology and visual sciences at the UBC faculty of medicine.
“But until now, there hasn’t been any data from large epidemiologic studies.”
Semaglutide, liraglutide
The US Food and Drug Administration approved the first GLP-1 agonist exenatide in 2005. Researchers are still learning about their other potential uses and benefits. The FDA hasn’t approved GLP-1 agonists for the treatment of Type 1 diabetes. Some healthcare providers prescribe it off-label.
The FDA currently approves the use of semaglutide and high-dose liraglutide to help treat obesity. Overweight is when you have a BMI of 25 to 29.9.
The British Columbia study also found a higher incidence of biliary disease, a group of conditions affecting the gall bladder, but the difference was not found to be statistically significant.
Though the events are rare, with millions around the world using the drugs, it could still lead to hundreds of thousands of people experiencing these conditions, according to the researchers.
“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,” said Dr Sodhi.
The findings were published in JAMA.
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