The approval of the GLP-1 receptor agonist semaglutide for weight regulation in January 2023 ushered in a new era of obesity therapy. In recent months, however,
“When millions of people are treated with medications like semaglutide, even relatively rare side effects occur in a large number of individuals,” Susan Yanovski, MD, codirector of the Office of Obesity Research at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, said in a JAMA news report.
Despite the low incidence of these adverse events and the likelihood that the benefits outweigh these risks in individuals with severe obesity, doctors and patients should be aware of these serious side effects, she added.
GLP-1 receptor agonists like semaglutide or liraglutide mimic certain intestinal hormones. Almost all their characteristic side effects involve the gastrointestinal tract: nausea, vomiting, constipation, and diarrhea. However, these are not the rare, severe side effects that are gaining increasing attention.
Severe Gastric Problems
A recent analysis published in JAMA shows that GLP-1 receptor agonists are associated with a ninefold higher risk of pancreatitis, compared with bupropion, an older weight-loss medication. Patients receiving GLP-1 receptor agonists also had four times more frequent intestinal obstruction and more than three times more frequent gastroparesis. The absolute risks for these complications, however, were less than 1% per year of use.
There were no indications of an increased risk for gallbladder diseases. Acute pancreatitis and acute gallbladder diseases are known complications of GLP-1 receptor agonists.
These results “reinforce that these are effective medications, and all medications have side effects,” said Dr. Yanovski. She emphasized that despite a significant increase in relative risk, however, the absolute risk remains very low.
Anesthetic Complications
In the spring of 2023, reports of patients taking GLP-1 receptor agonists and vomiting or aspirating food during anesthesia surfaced in some scientific journals. It was particularly noticeable that some of these patients vomited unusually large amounts of stomach contents, even though they had not eaten anything, as directed by the doctor before the operation.
Experts believe that the slowed gastric emptying intentionally caused by GLP-1 receptor agonists could be responsible for these problems.
The American Society of Anesthesiologists now recommends that patients do not take GLP-1 receptor agonists on the day of surgery and discontinue weekly administered agents like Wegovy 7 days before the procedure.
Increased Suicidality Risk?
In July, case reports of depression and suicidal ideation led the European Medicines Agency to investigate about 150 cases of potential self-harm and suicidal thoughts in patients who had received liraglutide or semaglutide. The review now also includes other GLP-1 receptor agonists. Results of the review process are expected in December.
Dr. Yanovski noted that it is unclear whether these incidents are caused by the drugs, but suicidal thoughts and suicidal behavior have also been observed with other medications for obesity treatment (eg, rimonabant). “It is certainly a good idea to use these medications cautiously in patients with a history of suicidality and monitor the patients accordingly,” she said.