New Research Warns of Heightened Risks of Gastrointestinal Complications in Diabetes Drugs Used for Weight Loss
Recent research conducted by the University of British Columbia has revealed that GLP-1 agonists, a type of diabetes medication often used off-label for weight loss, carry increased risks of severe gastrointestinal complications. The study focused on non-diabetic patients utilizing these drugs for weight loss and found elevated risks of pancreatitis, bowel obstruction, and gastroparesis. While these complications are rare, the large number of users globally means that a significant number of individuals could still be affected. In light of these findings, the researchers are advocating for clearer warning labels to ensure that patients are fully informed before using these medications.
The study, published in JAMA, is the first to investigate adverse gastrointestinal events in non-diabetic patients using GLP-1 agonists for weight loss on a population level. Previous studies had highlighted some of these risks in individuals with diabetes. First author Mohit Sodhi, a graduate of UBC’s experimental medicine program, emphasized the importance of considering these adverse events, as they can occur even if the patients are otherwise healthy. Sodhi suggested that the risk calculus may differ depending on whether the patient is using the drugs for diabetes, obesity, or general weight loss.
GLP-1 agonists were initially developed for managing Type 2 diabetes but have gained popularity in the past decade as an off-label weight-loss tool. In 2022 alone, approximately 40 million prescriptions were issued in the United States. Although certain forms of these medications were approved as treatments for obesity in 2021, randomized clinical trials assessing their efficacy for weight loss were not designed to capture rare gastrointestinal events due to limited sample sizes and short follow-up periods.
Dr. Mahyar Etminan, an epidemiologist and senior author of the study, highlighted anecdotal reports of patients experiencing repeated episodes of nausea and vomiting, known as gastroparesis, after using these drugs for weight loss. However, until now, there had been no data from large epidemiological studies available. To address this knowledge gap, the UBC researchers analyzed health insurance claim records for approximately 16 million U.S. patients who were prescribed semaglutide or liraglutide, two main GLP-1 agonists, between 2006 and 2020. The study focused on patients with a recent history of obesity and excluded those with diabetes or who had been prescribed another antidiabetic drug.
The analysis of the records revealed that compared to another weight loss drug, bupropion-naltrexone, GLP-1 agonists were associated with significantly higher risks of pancreatitis, bowel obstruction, and gastroparesis. Specifically, GLP-1 agonists were associated with a 9.09 times higher risk of pancreatitis, a 4.22 times higher risk of bowel obstruction, and a 3.67 times higher risk of gastroparesis. The study also found a higher incidence of biliary disease, affecting the gall bladder, although the difference was not statistically significant.
While these complications are rare, the researchers stress that with the large number of individuals using these drugs worldwide, hundreds of thousands of people could be at risk. The accessibility of these medications is also concerning, as some individuals can easily obtain them online without fully understanding the potential consequences. Hence, the researchers urge regulatory agencies and drug manufacturers to update the warning labels for these products to include the risk of gastroparesis.
Mohit Sodhi highlighted the critical nature of this information for patients, enabling them to seek timely medical attention and avoid serious consequences. The findings of this study serve as a crucial reminder to healthcare providers and individuals considering using GLP-1 agonists for weight loss to carefully weigh the potential risks and benefits and engage in informed decision-making.
Reference: “Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss” by Mohit Sodhi, Ramin Rezaeianzadeh, Abbas Kezouh and Mahyar Etminan, 5 October 2023, JAMA. DOI: 10.1001/jama.2023.19574