OBJECTIVES: To evaluate the risk of incident acute pancreatitis (AP) associated with the use of GLP-1 receptor agonists (GLP-1 RAs) liraglutide and semaglutide used for weight loss compared to bupropion/naltrexone fixed dose combination.

METHODS: We used data from the Merative MarketScan Commercial Claims and Encounters, and Medicare Supplemental databases. The study involved adults (≥18years) who began using GLP-1 RAs or bupropion/naltrexone from October 2016 to September 2021. We included individuals with an obesity diagnosis and no diabetes diagnosis or dispensing record in the preceding year. Also, those with diagnoses of AP, chronic pancreatitis, or pancreatic cancer within past 90 days were excluded. Patients were followed from treatment initiation until the onset of AP, treatment switching, discontinuation, disenrollment, or study end. We used inverse probability of treatment weighting (IPTW) to balance demographic and clinical factors across groups. Using a Cox proportional hazard model, we compared the association of AP between bupropion/naltrexone and GLP-1 RAs. We also performed separate evaluations for assessing AP risk in users of liraglutide and semaglutide.

RESULTS: We identified 35,377 users of GLP-1 RA (28,371 liraglutide; 7,006 semaglutide) and 14,526 users of the bupropion/naltrexone. Mean age was 45 years and 81% were female. Per 100,000 patient-year incidence of first AP event was 358 for GLP1 RA and 170 for bupropion/naltrexone users. The hazard ratio (HR) for AP among GLP-1 RA users compared to bupropion/naltrexone was 1.93 (95%CI 1.39, 2.67). When comparing specific GLP-1 RAs to bupropion/naltrexone, the HR for liraglutide was 2.02 (95%CI 1.46, 2.81) and was 1.42 (95%CI 0.80, 2.60) for semaglutide.

CONCLUSIONS: GLP-1 RAs are associated with a higher risk of AP compared to the bupropion/naltrexone. The risk varies between liraglutide and semaglutide, indicating the need for further research to understand these differences.