{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:43:25Z","timestamp":1792601005725,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>GLP\u20101 receptor agonists (GLP\u20101 RAs) are widely prescribed for type 2 diabetes and obesity, but their post\u2010marketing safety profile\u2014particularly psychiatric, vascular, neoplastic and rare ophthalmic events\u2014remains incompletely characterised and is vulnerable to confounding by indication, secondary\u2010suspect attribution and notoriety bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed 32 quarterly FAERS files (2018Q1\u20132025Q4): 288408 unique GLP\u20101 RA reports versus 11\u2009319\u2009150 non\u2010GLP\u20101 RA reports. Disproportionality used four methods (reporting odds ratio [ROR]; proportional reporting ratio [PRR]; Bayesian Confidence Propagation Neural Network information component, lower 95% bound [BCPNN IC025]; Multi\u2010item Gamma Poisson Shrinker empirical Bayes lower 5th\u2010percentile bound [MGPS EB05]; signal\u2009=\u2009\u2265\u20093 of 4). The top 30 ROR\u2010ranked signals were stratified by primary\u2010suspect (PS) sensitivity. Triangulation included active\u2010comparator, intra\u2010class psychiatric comparison, interrupted time\u2010series assessment of reporting around the 2023 EMA announcement, Weber\u2010effect evaluation with Cochran\u2013Armitage trend testing, and external validation in JADER.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 22\u2009059 PT\u2013class pairs, 544 met the \u2265\u20093\u2010of\u20104 criterion. PS\u2010stratification retained 21 of the top 30 signals and demoted 9 as secondary\u2010suspect\u2010driven (e.g., capillaritis ROR 18.6\u2009\u2192\u20090.27; heart sounds 84.3\u2009\u2192\u20090.55). PS\u2010stable headline signals were dominated by gastrointestinal\/hepatobiliary effects: cyclic vomiting syndrome (ROR 64.8; semaglutide\u2010dominant), gallbladder injury (84.2), impaired gastric emptying (45.1), plus liraglutide\u2010concentrated medullary thyroid cancer (41.1) and semaglutide\u2010concentrated optic ischaemic neuropathy (26.5). Only semaglutide carried a class\u2010level suicidal\u2010ideation signal (ROR 2.30). Interrupted time series detected no level (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.39) or slope change (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.75) at the 2023 EMA announcement; psychiatric time\u2010to\u2010onset (median 47\u2009days) aligned with early GI reactions. Sixteen of 17 priority signals (94.1%) replicated in JADER. As disproportionality analyses, these are hypothesis\u2010generating safety signals and cannot establish incidence, relative risk, or causality.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71138","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T03:25:03Z","timestamp":1784690703000},"page":"9251-9264","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety Signals of\n                    <scp>GLP<\/scp>\n                    \u20101 Receptor Agonists: A Multi\u2010Method Pharmacovigilance Analysis of\n                    <scp>FAERS<\/scp>\n                    (2018\u20132025) With Sensitivity\u2010Stratified Prioritisation, Notoriety\u2010Bias Assessment, and Cross\u2010Database Validation"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2094-220X","authenticated-orcid":false,"given":"Shiyi","family":"Xu","sequence":"first","affiliation":[{"name":"Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.01.004"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603827"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607141"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31149-3"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)01443-4"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206038"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2307563"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2032183"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200932020-00003"},{"key":"e_1_2_11_11_1","unstructured":"European Medicines Agency \u201cGLP\u20101 Receptor Agonists: Review of Reports of Suicidal Thoughts and Self\u2010Harm \u201dEMA\/PRAC July 2023 updated November 2023."},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.therap.2019.01.006"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.668"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.677"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1742"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200225060-00001"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/00031305.1999.10474456"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.24"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2710.2002.00430.x"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280211403604"},{"key":"e_1_2_11_21_1","first-page":"1","article-title":"Epidemiology of Adverse Reactions to Nonsteroidal Antiinflammatory Drugs","volume":"6","author":"Weber J. 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