Glucagon-like peptide 1 receptor agonists and the potential risk of pancreatic carcinoma: a pharmacovigilance study using theFDA Adverse Event Reporting System and literature visualization analysis.

Abstract

There are increasing data on the potential risk of pancreatic carcinoma associated with glucagon-like peptide 1 receptor agonists (GLP-1RAs). The study aimed to determine whether GLP-1RAs are associated with increased detection of pancreatic carcinoma based on the FDA Adverse Events Reporting System and clarify its potential mechanisms through keyword co-occurrence analysis from literature database. Disproportionality and Bayesian analyses were used for signal detection using reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayesian geometric mean (EBGM). Mortality, life-threatening events, and hospitalizations were also investigated. VOSviewer was adopted to generate visual analysis of keyword hotspots. A total of 3073 pancreatic carcinoma cases were related to GLP-1RAs. Five GLP-1RAs were detected with signals for pancreatic carcinoma. Liraglutide had the strongest signal detection (ROR 54.45, 95% CI 51.21-57.90; PRR 52.52, 95% CI 49.49-55.73; IC 5.59; EBGM 48.30). The signals of exenatide (ROR 37.32, 95% CI 35.47-39.28; PRR 36.45, 95% CI 34.67-38.32; IC 5.00; EBGM 32.10) and lixisenatide (ROR 37.07, 95% CI 9.09-151.09; PRR 36.09; 95% CI 9.20-141.64; IC 5.17, EBGM 36.09) were stronger than those of semaglutide (ROR 7.43, 95% CI 5.22-10.57; PRR 7.39; 95% CI 5.20-10.50; IC 2.88, EBGM 7.38) and dulaglutide (ROR 6.47, 95% CI 5.56-7.54; PRR 6.45; 95% CI 5.54-7.51; IC 2.67, EBGM 6.38). The highest mortality rate occurred in exenatide (63.6%). Based on the bibliometric investigation, cAMP/protein-kinase, Ca2+ channel, endoplasmic-reticulum stress, and oxidative stress are potential pathogenesis of pancreatic carcinoma resulting from GLP-1RAs. Based on this pharmacovigilance study,GLP-1RAs, except albiglutide, are associated with pancreatic carcinoma.