Evidence map›Paper›PMID 42420795›Full record

ArticleDiabetes, obesity & metabolism2026

Neuropsychiatric Outcomes With Tirzepatide, Semaglutide, and Other GLP-1 Receptor Agonists.

Solomon Chih-Cheng Chen, Tso-Jen Wang, Chu-Kuang Chou, Chun Lee

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Article in Diabetes, obesity & metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Solomon Chih-Cheng ChenDepartment of Pediatrics, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan.ORCID 0000-0003-0031-6147
Tso-Jen WangDepartment of Psychiatry, Chiayi Branch, Taichung Veterans General Hospital, Chiayi City, Taiwan.
Chu-Kuang ChouDepartment of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan.ORCID 0000-0003-2588-6883
Chun LeeClinical Data Center, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsNeuropsychiatric safety concerns, including depression and suicidal ideation, have emerged during the expanding clinical use of incretin-based therapies for type 2 diabetes mellitus (T2DM) and obesity. However, whether risks differ across successive generations of incretin-based therapies remains uncertain. MATERIALS AND

methodsThis retrospective cohort study used the TriNetX Global Federated Network (> 192 million patients). Adults with T2DM, obesity, or both initiating tirzepatide, semaglutide, or other glucagon-like peptide-1 receptor agonists (GLP-1 RAs) between July 2022 and June 2025 were identified using a new-user design with a 12-month washout. Propensity score matching balanced demographic, clinical, and metabolic variables. Two comparisons were conducted: tirzepatide versus semaglutide and semaglutide versus other GLP-1 RAs. Follow-up included Year 1 (day 31-365) and Year 2 landmark analysis (day 366-730). Hazard ratios (HRs) for incident depression, anxiety, and suicidal ideation were estimated using Cox models.

resultsAfter matching, 85 546 pairs were included for tirzepatide versus semaglutide and 80 115 pairs for semaglutide versus other GLP-1 RAs. Tirzepatide and semaglutide showed similar risks for the composite psychiatric outcome (Year 1 HR 0.984 [95% CI 0.950-1.019]; Year 2 HR 1.002 [0.960-1.046]); a nominally higher anxiety hazard was observed with tirzepatide during Year 2 (HR 1.052 [1.001-1.106]), which should be interpreted cautiously given multiple comparisons. Compared with other GLP-1 RAs, semaglutide was associated with lower risks of depression (HR 0.811 [0.770-0.855]), anxiety (HR 0.915 [0.871-0.961]), suicidal ideation (HR 0.488 [0.339-0.702]), and the composite psychiatric outcome (HR 0.866 [0.832-0.901]) during Year 1.

conclusionsIn real-world practice, tirzepatide and semaglutide demonstrated comparable neuropsychiatric risk profiles over 2 years. Semaglutide was associated with lower psychiatric event rates compared with earlier-generation GLP-1 receptor agonists.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsGlucagon-Like PeptidesHypoglycemic AgentsObesityTirzepatideAdultAgedAnxietyDepressionFemaleHumansIncretinsMaleMiddle AgedRetrospective StudiesGlucagon-Like Peptide-1 Receptor AgonistsGlucagon-Like PeptidesHypoglycemic AgentsIncretinsSemaglutideTirzepatidecohort studiescomparative effectiveness researchdepressive disorderglucagon‐like peptide‐1 receptor agonistspostmarketing surveillancereal‐world evidencesuicidal ideation

Identifiers

PMID42420795
PMCPMC13538802

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.