News Brief: Gastrointestinal Adverse Events Associated with New Weight Loss Drugs

Recent articles in Worst Pills, Best Pills News have discussed the risks of new weight loss drugs, including substantial weight regain if the medications are stopped. Developed and initially approved for type 2 diabetes as an adjunct to diet and exercise to improve glycemic control, the FDA subsequently approved liraglutide (SAXENDA) and then semaglutide (WEGOVY) for chronic weight management.[1] Tirzepatide (MOUNJARO), another type 2 diabetes drug, has not been approved for chronic weight management but has been studied for the treatment of obesity.[2] Recently, more information about the adverse effects of some of these drugs has become available.

Liraglutide, semaglutide and tirzepatide are of a class of drugs known as glucagon-like peptide-1 (GLP-1) receptor agonists (activators); tirzepatide also has additional actions. A research letter, published in October 2023 in JAMA, reported on the risk of gastrointestinal adverse events associated with use of GLP-1 agonists for weight loss.[3] Using a random sample of 16 million patients from a large health care database that captures most outpatient prescriptions and physician diagnoses in the United States, the researchers assembled a cohort of 4,144 users of liraglutide, 613 users of semaglutide and 654 users of bupropion-naltrexone (CONTRAVE), a combination of an antidepressant and an opioid antagonist, which is also approved by the FDA for weight loss. All the GLP-1 agonists users had a record of obesity without diabetes. Compared to the use of bupropion-naltrexone, the study found that use of GLP-1 agonists was associated with substantially increased risks of pancreatitis (inflammation of the pancreas), gastroparesis (paralysis of the stomach) and bowel obstruction, but not gall bladder and bile duct disease. These adverse events were infrequent, with an incidence (new onset) in the range of 5 to 20 events per 1000 years of people using a GLP-1 agonist. Nonetheless, they should be considered by individuals who are contemplating using these drugs for weight loss. To prevent regaining weight, lifetime use of a GLP-1 agonist may be required. As these are relatively new drugs, more will become known about their adverse effects and drug interactions as more people take the drugs for longer periods of time.
 

References

[1] Semaglutide (WEGOVY) for weight loss; substantial risks including weight regain. Worst Pills, Best Pills News, August 2023.

[2] Tirzepatide (MOUNJARO): Another diabetes drug seeking FDA Approval for weight loss. Worst Pills, Best Pills News, October 2023.

[3] Sodhi M, Rezaeianzadeh R, Kezouh A, Etminan M. Risk of gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists for weight loss. JAMA. Published online October 5, 2023. doi:10.1001/jama.2023.19574.