Drug-associated pancreatic cancer: insights from real-world pharmacovigilance and network pharmacology

Pancreatic cancer's high mortality rate necessitates our study, which aims to identify potential risk drugs and speculate on the underlying mechanisms. All pertinent reports from the FDA Adverse Event Reporting System database were extracted. The disproportionality analysis was used in signal detection and data on patient age, sex, weight, time to onset were collected. Seven databases were retrieved for network pharmacology. AutoDock Vina 1.1.2 was for molecular docking. Signals were detected among 397 drugs with pancreatic cancer report ≥3. Except 4 antineoplastic agents, only 24 drugs indicated pancreatic cancer signals in 33,948 reports including 4 dipeptidyl peptidase-4 (DPP-4) inhibitors, 3 glucagon-like peptide-1 (GLP-1) analogues, 5 compound hypoglycemic agents, 3 hypotensive agents, ranitidine, pancrelipase, fondaparinux, naldemedine, daprodustat, megestrol acetate, leuprorelin, lecanemab, and lorcaserin. Pancreatic cancer more occurred after the age of 45, with a higher proportion among male. Weight with GLP-1 analogues (median, 91 kg), and compound hypoglycemic agents (median, 82 kg) was heavier (p < 0.01). GLP1R (glucagon-like peptide 1 receptor) for GLP-1 analogues, and PTEN (phosphatase and tensin homolog) for metformin might be a potential cause of pancreatic cancer. Clinicians providing these therapies should stay vigilant to detect pancreatic cancer early.