{"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":1792601005653,"version":"4.5.0"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"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>Aims<\/jats:title>\n                    <jats:p>Neuropsychiatric safety concerns, including depression and suicidal ideation, have emerged during the expanding clinical use of incretin\u2010based therapies for type 2 diabetes mellitus (T2DM) and obesity. However, whether risks differ across successive generations of incretin\u2010based therapies remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study used the TriNetX Global Federated Network (&gt;\u2009192 million patients). Adults with T2DM, obesity, or both initiating tirzepatide, semaglutide, or other glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101 RAs) between July 2022 and June 2025 were identified using a new\u2010user design with a 12\u2010month washout. Propensity score matching balanced demographic, clinical, and metabolic variables. Two comparisons were conducted: tirzepatide versus semaglutide and semaglutide versus other GLP\u20101 RAs. Follow\u2010up included Year 1 (day 31\u2013365) and Year 2 landmark analysis (day 366\u2013730). Hazard ratios (HRs) for incident depression, anxiety, and suicidal ideation were estimated using Cox models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After matching, 85\u2009546 pairs were included for tirzepatide versus semaglutide and 80\u2009115 pairs for semaglutide versus other GLP\u20101 RAs. Tirzepatide and semaglutide showed similar risks for the composite psychiatric outcome (Year 1 HR 0.984 [95% CI 0.950\u20131.019]; Year 2 HR 1.002 [0.960\u20131.046]); a nominally higher anxiety hazard was observed with tirzepatide during Year 2 (HR 1.052 [1.001\u20131.106]), which should be interpreted cautiously given multiple comparisons. Compared with other GLP\u20101 RAs, semaglutide was associated with lower risks of depression (HR 0.811 [0.770\u20130.855]), anxiety (HR 0.915 [0.871\u20130.961]), suicidal ideation (HR 0.488 [0.339\u20130.702]), and the composite psychiatric outcome (HR 0.866 [0.832\u20130.901]) during Year 1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In real\u2010world practice, tirzepatide and semaglutide demonstrated comparable neuropsychiatric risk profiles over 2\u2009years. Semaglutide was associated with lower psychiatric event rates compared with earlier\u2010generation GLP\u20101 receptor agonists.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71088","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T03:41:16Z","timestamp":1783568476000},"page":"8895-8904","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Neuropsychiatric Outcomes With Tirzepatide, Semaglutide, and Other\n                    <scp>GLP<\/scp>\n                    \u20101 Receptor Agonists"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0031-6147","authenticated-orcid":false,"given":"Solomon Chih\u2010Cheng","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pediatrics Ditmanson Medical Foundation Chia\u2010Yi Christian Hospital  Chiayi City Taiwan"},{"name":"Department of Pediatrics, College of Medicine Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tso\u2010Jen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Chiayi Branch Taichung Veterans General Hospital  Chiayi City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2588-6883","authenticated-orcid":false,"given":"Chu\u2010Kuang","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Ditmanson Medical Foundation Chia\u2010Yi Christian Hospital  Chiayi City Taiwan"},{"name":"Obesity Center Ditmanson Medical Foundation Chia\u2010Yi Christian Hospital  Chiayi City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Data Center Ditmanson Medical Foundation Chia\u2010Yi Christian Hospital  Chiayi City 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