Evaluating the Rates of Pancreatitis and Pancreatic Cancer Among GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Abstract

Aims: This meta-analysis evaluates the rates of pancreatitis/pancreatic cancer among glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in randomised controlled trials (RCTs). Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic search was performed in PubMed, Embase, and Cochrane Library for GLP-1 RA RCTs that evaluated pancreatitis/pancreatic cancer. A meta-analysis was conducted to evaluate this risk; subgroup analysis was performed with and without background medications. Results: 62 studies utilising dulaglutide, exenatide, liraglutide, semaglutide, beinaglutide, retatrutide, or tirzepatide, with 66,232 patients, mean age of 58.3 years (14.4 to 68), and mean follow-up of 43.5 weeks (1 to 198) were included in this study. Meta-analysis showed a significantly increased risk of pancreatitis (RR: 1.44, 95% CI 1.09–1.89, p = 0.009), but not when stratified by background medications (RR: 1.28, 95% CI 0.87–1.87) and without background medications (RR: 1.37, 95% CI 0.91–2.05). Pancreatic cancer and GLP-1 RA use showed no significant association (RR: 1.30, 95% CI 0.86–1.97). However, a significant increase was found with background medications (RR: 1.85, 95% CI 1.05–3.26, p = 0.03), but not without (RR: 0.81, 95% CI 0.43–1.55). Conclusion: GLP-1 RAs carry a slightly increased risk of pancreatitis, which is not significant when stratified by background medication use. Overall risk for pancreatic cancer was not observed, but a slight association was found when stratified with background medications. However, this difference is likely minimal, given the numerous studies excluded from the meta-analysis where both treatment arms had zero events.