{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:43:56Z","timestamp":1792601036857,"version":"4.5.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Incretin-based therapies, including glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, are essential treatments in diabetes management due to their efficacy in glycemic control and the additional benefits of GLP-1 RAs, which include cardiovascular and renal protection. However, concerns about potential associations with biliary disorders necessitate ongoing pharmacovigilance. This study analyzes the link between these drugs and biliary adverse events (AEs) using the FDA Adverse Event Reporting System (FAERS) to enhance clinical safety.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We extracted AE data for GLP-1 RAs and DPP-4 inhibitors from FAERS between Q1 2013 and Q1 2024 using OpenVigil 2.1. Analytical methods such as the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) were employed to assess AE risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A search of biliary disorders by standard MedDRA analytical queries (SMQs) identified 2,215 reports of biliary AEs, with 1,709 related to GLP-1 RAs and 506 to DPP-4 inhibitors. DPP-4 inhibitors showed a significant association with biliary disorders (ROR, 3.09; 95% CI, 2.83\u20133.37), particularly sitagliptin (ROR, 3.46; 95% CI, 3.13\u20133.83). Although the overall association for GLP-1 RAs (ROR, 1.60; 95% CI, 1.52\u20131.68) was not significant, semaglutide (ROR, 4.06; 95% CI, 3.76\u20134.39) and liraglutide (ROR, 3.88; 95% CI, 3.50\u20134.29) indicated a notable risk. The SMQ subgroup analyses of sitagliptin, semaglutide, and liraglutide with the SMQ subgroup categories of \u201cbiliary tract disorders,\u201d \u201cgallbladder related disorders,\u201d \u201cgallstone related disorders,\u201d and \u201cinfectious biliary disorders\u2019 demonstrated a statistically significant correlation. Notably, liraglutide, alogliptin, sitagliptin, and linagliptin were linked to \u201cbiliary malignant tumors\u201d with statistical significance. The proportion of serious outcomes was higher for DPP-4 inhibitors (n = 389, 76.88%) compared to GLP-1 RAs (n = 881, 51.55%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>DPP-4 inhibitors are potentially linked to biliary disorders, warranting vigilance. While the overall association for GLP-1 RAs was not significant, specific drugs like semaglutide, liraglutide, and sitagliptin showed concerning signals, suggesting a need for heightened awareness among clinicians regarding the risk of biliary AEs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1509561","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T06:47:08Z","timestamp":1739774828000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Association between GLP-1 RAs and DPP-4 inhibitors with biliary disorders: pharmacovigilance analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Long","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"k4880","DOI":"10.1136\/bmj.k4880","article-title":"Incretin based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: population based cohort study","volume":"363","author":"Abrahami","year":"2018","journal-title":"BMJ"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e0157753","DOI":"10.1371\/journal.pone.0157753","article-title":"OpenVigil FDA - inspection of U.S. American adverse drug events pharmacovigilance data and novel clinical applications","volume":"11","author":"B\u00f6hm","year":"2016","journal-title":"PloS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"354","DOI":"10.4093\/dmj.2023.0277","article-title":"Glucagon-like peptide-1: new regulator in lipid metabolism","volume":"48","author":"Bu","year":"2024","journal-title":"Diabetes Metab."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1330936","DOI":"10.3389\/fendo.2024.1330936","article-title":"Psychiatric adverse events associated with GLP-1 receptor agonists: a real-world pharmacovigilance study based on the FDA Adverse Event Reporting System database","volume":"15","author":"Chen","year":"2024","journal-title":"Front. 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