Article

Abstract

  • This study investigates gastrointestinal adverse events associated with glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, liraglutide) used for weight loss.

  • GLP-1 agonists are approved for diabetes treatment but increasingly used off-label for weight loss.

  • Previous studies indicate increased risks of gastrointestinal issues (biliary diseases, pancreatitis, bowel obstruction, gastroparesis) in diabetes patients.

  • Importance of understanding risks for non-diabetic obese patients considering GLP-1 agonist use.

Methods

  • A cohort of 16 million patients between 2006-2020 from the PharMetrics Plus database was analyzed, capturing 93% of U.S. outpatient prescriptions.

  • Included new users of semaglutide/liraglutide and the active comparator bupropion-naltrexone.

  • Cohort ensured patients had an obesity code while excluding diabetes treatment codes.

  • Patients monitored from first prescription until the first incidence of gastrointestinal adverse events, defined by ICD-9 or ICD-10 codes.

Results

  • Our cohort consisted of: 4144 liraglutide users, 613 semaglutide users, and 654 bupropion-naltrexone users.

  • Incidence rates of key outcomes per 1000 person-years:

    • Biliary disease:

      • Semaglutide: 11.7

      • Liraglutide: 18.6

      • Bupropion-naltrexone: 12.6

    • Pancreatitis:

      • Semaglutide: 4.6

      • Liraglutide: 7.9

      • Bupropion-naltrexone: 1.0

    • Bowel obstruction and gastroparesis rates showed a heightened incidence in GLP-1 users compared to bupropion-naltrexone.

Discussion

  • GLP-1 agonists show increased risk of pancreatitis, bowel obstruction, and gastroparesis but not biliary disease compared to bupropion-naltrexone.

  • The necessity for patients to weigh risks against benefits when considering GLP-1 agonists for weight loss is highlighted.

  • Limitations include uncertainty if GLP-1s were solely for weight loss in this patient group.

Conclusion

  • With the growing utilization of GLP-1 drugs for weight loss, it’s crucial for healthcare providers to communicate risks of rare adverse events to potential users considering treatment for obesity.

References

  • Listing of various studies and literature surrounding the use of GLP-1 agonists and their associated risks identified in the article.