{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:04:17Z","timestamp":1781071457259,"version":"3.54.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"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. Drug Saf. Regul."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Drug-induced pancreatitis remains a clinically important condition owing to its severity and relevance to pharmacotherapeutic risk management. Incretin-based antidiabetic agents, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, are associated with an increased risk of acute pancreatitis (AP). However, the extent to which concomitant medication modifies AP has not yet been systematically elucidated. We conducted a comprehensive systematic drug\u2013drug interaction (DDI) assessment involving GLP-1 RA and DPP-4 inhibitors using the U.S. Food and Drug Administration\u2019s Adverse Event Reporting System (FAERS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Disproportionality analyses were conducted using the FAERS data (JAPIC FAERS) from the fourth quarter of 1997 to the first quarter of 2024. Crude reporting odds ratios (cRORs) were calculated to assess the association between individual drugs and AP. DDI signals for 1:1 concomitant use involving GLP-1 RAs or DPP-4 inhibitors were comprehensively evaluated using the \u03a9 shrinkage measure, with \u03a9\n                      <jats:sub>025<\/jats:sub>\n                      as the signal detection criterion. \u03a9\n                      <jats:sub>025<\/jats:sub>\n                      were analyzed for all pooled cases, and temporal trends were assessed across six multi-year periods using a period-stratified analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Elevated cRORs for AP were observed for several agents, including GLP-1 RAs, DPP-4 inhibitors, and other antidiabetic medications. Pairwise DDI analyses of GLP-1 RAs or DPP-4 inhibitors with other drugs identified positive interaction signals in 308 drug pairs in pooled analyses. Period-stratified analyses narrowed the findings to 11 drug pairs with consistent signals across \u22653 of 6 periods, including dulaglutide\u2013atorvastatin (four periods). However, no concomitant drug combinations involving GLP-1 RAs or DPP-4 inhibitors were identified as being robustly associated with increased AP reporting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Period-stratified analysis helped mitigate false-positive signals identified in the pooled DDI analyses. Drug pairs exhibiting recurrent weak AP signals warrant continued pharmacovigilance and further evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fdsfr.2026.1827098","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T05:41:40Z","timestamp":1781070100000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive pharmacovigilance assessment of pairwise drug\u2013drug interactions and acute pancreatitis in the FDA adverse event reporting system: focus on incretin-based drugs"],"prefix":"10.3389","volume":"6","author":[{"given":"Issei","family":"Kazume","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences","place":["Tokyo, Japan"]},{"name":"P-One Clinic, Keikokai Medical Corp","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Onda","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Yokokawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1093\/jnci\/87.9.689-a","article-title":"Pancreatitis associated with ondansetron","volume":"87","author":"Alberti-Flor","year":"1995","journal-title":"J. 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