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Meta-Analysis
. 2025 Sep;8(5):e70113.
doi: 10.1002/edm2.70113.

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

Jimmy Wen  1 , Denise Nadora  1 , Ethan Bernstein  1 , Christiane How-Volkman  1 , Alina Truong  1 , Bethany Joy  1 , Megan Kou  1 , Zohaer Muttalib  1 , Arsh Alam  2 , Eldo Frezza  1
Affiliations
Meta-Analysis

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

Jimmy Wen et al. Endocrinol Diabetes Metab. 2025 Sep.

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.

Keywords: GLP‐1 RA; pancreatic cancer; pancreatitis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
PRISMA Diagram of the included studies.
FIGURE 2
FIGURE 2
Meta‐analysis of GLP‐1 RA versus control for comparison of pancreatitis incidence.
See this image and copyright information in PMC

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