A new study published in JAMA has found that using glucagon-like peptide-1 (GLP-1) receptor agonists for weight loss may increase the risk of developing pancreatitis, gastroparesis, and bowel obstruction. These drugs are commonly prescribed to treat type 2 diabetes and obesity, but their long-term safety and effectiveness are not well established.
What are GLP-1 receptor agonists?
GLP-1 receptor agonists are a class of drugs that mimic the action of a hormone called glucagon-like peptide-1, which stimulates insulin secretion and reduces appetite. They are injected under the skin once or twice a day, or once a week, depending on the type of drug. Some examples of GLP-1 receptor agonists are liraglutide, semaglutide, dulaglutide, and exenatide.
These drugs have been shown to lower blood sugar levels and help people with type 2 diabetes and obesity lose weight. However, they also have some side effects, such as nausea, vomiting, diarrhea, constipation, and injection site reactions. In rare cases, they may also cause inflammation of the pancreas (pancreatitis), delayed emptying of the stomach (gastroparesis), or blockage of the intestines (bowel obstruction).
What did the study find?
The study was conducted by researchers from the University of British Columbia in Vancouver, Canada. They analyzed data from more than 400,000 people who used GLP-1 receptor agonists or another weight loss drug called bupropion-naltrexone between 2010 and 2020 in the United States. They compared the rates of hospitalization for gastrointestinal adverse events among the two groups of users.
The results showed that GLP-1 receptor agonists were associated with a higher risk of pancreatitis, gastroparesis, and bowel obstruction than bupropion-naltrexone. The absolute risk difference was 0.6 per 1,000 person-years for pancreatitis, 0.4 per 1,000 person-years for gastroparesis, and 0.3 per 1,000 person-years for bowel obstruction. This means that for every 1,000 people who used GLP-1 receptor agonists for one year, there were 0.6 more cases of pancreatitis, 0.4 more cases of gastroparesis, and 0.3 more cases of bowel obstruction than those who used bupropion-naltrexone.
The researchers adjusted for various factors that could affect the results, such as age, sex, body mass index, smoking status, alcohol use, and comorbidities. They also performed several sensitivity analyses to test the robustness of their findings. They found that the associations were consistent across different subgroups and scenarios.
What are the implications of the study?
The study suggests that GLP-1 receptor agonists may have some serious gastrointestinal side effects that could outweigh their benefits for weight loss. The researchers noted that these adverse events are rare, but they could be life-threatening and require hospitalization. They also pointed out that the risk-benefit balance may differ for people who use these drugs for diabetes versus those who use them for obesity.
The researchers recommended that patients who are considering using GLP-1 receptor agonists for weight loss should be informed about the potential risks and monitored closely for any signs of gastrointestinal problems. They also called for more long-term studies to evaluate the safety and effectiveness of these drugs in different populations and settings.
The study was funded by the Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research.