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.