Glucagon-like peptide-1 receptor agonists and risk of pancreaticobiliary cancers in patients with type 2 diabetes: a nationwide cohort study

초록

Aim: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated substantial metabolic benefits, but their association with pancreaticobiliary cancer risk remains unclear. We investigated the association between GLP-1RA use and pancreaticobiliary cancer incidence in patients with type 2 diabetes (T2D). Methods: This population-based cohort study used Korean National Health Insurance Service data from 2011 to 2023. We identified 51,780 patients with T2D receiving metformin plus sulfonylurea who initiated either GLP-1RA (n=24,052) or dipeptidyl peptidase-4 inhibitor (DPP-4i, n=27,728). The primary outcomes were incident pancreatic cancer, bile duct cancer, gallbladder cancer, and composite pancreaticobiliary cancer. Hazard ratios (HRs) were estimated using Cox proportional hazards models adjusted for demographics, comorbidities, and previous diabetes medications. Results: During 208,992 person-years of follow-up (mean 4.0 years), 321 pancreaticobiliary cancers occurred. GLP-1RA use was associated with a significantly lower risk of pancreatic cancer (adjusted HR 0.668, 95% CI 0.476-0.939). Similar trends were observed for bile duct cancer (adjusted HR 0.649, 95% CI 0.375-1.124), gallbladder cancer (adjusted HR 0.418, 95% CI 0.171-1.019), and composite pancreaticobiliary cancer (adjusted HR 0.681, 95% CI 0.515-0.901). These associations remained consistent in a propensity score-matched analysis and after excluding patients with baseline pancreaticobiliary disease. Conclusion: In this large cohort study, GLP-1RA use was associated with reduced pancreatic cancer risk compared with DPP-4i use among patients with T2D. Similar trends were observed for other pancreaticobiliary cancers. These findings suggest potential protective effects that warrant confirmation in longer-term studies.

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