Glucagon-like Peptide-1 receptor agonists are not associated with increased risk of pancreatic cancer: A systematic review and meta-analysis

Gaetano Lauri; Paolo Giorgio Arcidiacono; Antonio Facciorusso; Gabriele Capurso; Matteo Tacelli

doi:10.1016/j.pan.2026.04.005

Glucagon-like Peptide-1 receptor agonists are not associated with increased risk of pancreatic cancer: A systematic review and meta-analysis

Pancreatology. 2026 Apr 6:S1424-3903(26)00147-X. doi: 10.1016/j.pan.2026.04.005. Online ahead of print.

Authors

Gaetano Lauri¹, Paolo Giorgio Arcidiacono¹, Antonio Facciorusso², Gabriele Capurso¹, Matteo Tacelli³

Affiliations

¹ Pancreatico-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research, Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
² Department of Experimental Medicine, Università del Salento, Lecce, Italy.
³ Pancreatico-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research, Center, IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: tacelli.matteo@hsr.it.

PMID: 41991368
DOI: 10.1016/j.pan.2026.04.005

Abstract

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for glucose control and weight management. Concerns have arisen regarding a potential association with pancreatic ductal adenocarcinoma (PDAC), though evidence remains conflicting. We performed a systematic review and meta-analysis to evaluate PDAC risk in GLP-1 RA users.

Methods: We included studies with ≥24 weeks of follow-up assessing PDAC incidence in patients treated with GLP-1 RAs. Eligible studies included adults with type 2 diabetes or obesity. Pooled estimates were calculated using random-effects models. Heterogeneity was assessed with I², publication bias with Egger's test, and meta-regression explored potential effect modifiers.

Results: Sixty studies (49 randomized trials and 11 observational cohorts) including 4,932,290 patients (2,281,546 GLP-1 RA users; 2,650,744 non-users) were analyzed. GLP-1 RA use was not associated with an increased PDAC risk overall (OR 0.688, 95% CI 0.575-0.824; I² = 69.4%). An inverse association was observed mainly in observational cohorts, in overweight/obese patients with diabetes, and with prolonged exposure (>52 weeks) and follow-up (>60 weeks). Meta-regression confirmed treatment duration and indication as significant modifiers. Egger's test (p = 0.829) excluded publication bias.

Conclusions: GLP-1 RA therapy was not associated with an increased risk of PDAC. Observational data suggest a possible inverse association, although further high-quality studies are warranted.

Keywords: Cancer risk; Diabetes; GLP-1 receptor agonists; Obesity; Pancreatic ductal adenocarcinoma.