{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:03:30Z","timestamp":1790071410180,"version":"4.0.1"},"reference-count":31,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Pers. Med.","JPM"],"abstract":"<jats:p>Introduction: Association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and pancreatitis and its long-term complications remains controversial. Using a global electronic health record database, we evaluated pancreatic outcomes following GLP-1 RA initiation in adults with type 2 diabetes mellitus (T2DM). Methods: Adults aged \u226518 years who were alive at the index date; T2DM patients initiating GLP-1 RAs between 2013 and 2025 were identified in the TriNetX network and compared with patients initiating sodium\u2013glucose cotransporter-2 inhibitors (SGLT2i). Sensitivity analyses included comparisons with other second-line diabetes therapies, excluding dipeptidyl peptidase-4 inhibitors, and analyses were restricted to U.S.-based health care organizations. Patients with pre-existing pancreatic conditions were excluded. Cohorts were propensity score-matched for treatment indications, pancreatitis risk factors, and demographics. Kaplan\u2013Meier and Cox proportional hazard models evaluated acute pancreatitis (overall and biliary), chronic pancreatitis, pancreatic pseudocyst, and pancreatic cancer. Results: After matching, 291,152 patients were included in each cohort. GLP-1 RA initiation was not associated with an increased hazard of overall acute pancreatitis compared with SGLT2i initiation (HR 1.095; 95% CI 0.996\u20131.204), with concordant Kaplan\u2013Meier analyses. A modest, etiology-specific increase in biliary acute pancreatitis was observed in the primary comparison (HR 1.276; 95% CI 1.010\u20131.612) but was not consistent across sensitivity analyses. No differences were observed in the risks of pancreatic pseudocyst (HR 0.729; 95% CI 0.525\u20131.014) or pancreatic cancer (HR 1.069; 95% CI 0.940\u20131.215). Results were similarly consistent in sensitivity analyses. Conclusion: GLP-1 RAs are not associated with an increased risk of acute pancreatitis, pancreatitis-related complications, or pancreatic cancer in T2DM adults; a modest biliary pancreatitis signal was observed, but was not consistent across sensitivity analyses.<\/jats:p>","DOI":"10.3390\/jpm16090478","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:50:27Z","timestamp":1789566627000},"page":"478","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glucagon-like Peptide-1 Receptor Agonists Are Not Associated with Increased Risk of Acute Pancreatitis or Pancreatic Complications, Including Pancreatic Cancer, in Type 2 Diabetes: A Global Propensity-Matched Cohort Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Yan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Medicine, MetroHealth Medical Center and Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Benjamin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, MetroHealth Medical Center and Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Hanyou","family":"Loh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Canton Medical Education Foundation, Canton, OH 44710, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Samantha","family":"Mathialagan","sequence":"additional","affiliation":[{"name":"Department of Medicine, MetroHealth Medical Center and Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3817-2751","authenticated-orcid":false,"given":"Cindy Hsin-Ti","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medicine, MetroHealth Medical Center and Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Yasir","family":"Tarabichi","sequence":"additional","affiliation":[{"name":"Center for Clinical Informatics Research and Education, MetroHealth Medical Center and Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Donovan","family":"Veccia","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, MetroHealth Medical Center and Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Richard","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, MetroHealth Medical Center and Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"William","family":"Tse","sequence":"additional","affiliation":[{"name":"Gene and Cell Therapy Institute, MetroHealth Medical Center and Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Division of Medical Oncology, MetroHealth Medical Center and Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5551-1818","authenticated-orcid":false,"given":"Gengqing","family":"Song","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, MetroHealth Medical Center and Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee (2022). 9. 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