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. 2025 Nov 17:16:1626103.
doi: 10.3389/fpsyt.2025.1626103. eCollection 2025.

Association of tirzepatide and the risk of suicide in a real-world cohort

Wei-Shin Yu  1 , Jing-Yang Huang  2 , Shih-Chang Lo  1 , Chien-Ning Huang  1   3   4 , Yi-Sun Yang  1   3 , Edy Kornelius  1   3
Affiliations

Association of tirzepatide and the risk of suicide in a real-world cohort

Wei-Shin Yu et al. Front Psychiatry. .

Abstract

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists, including tirzepatide, are increasingly prescribed for obesity and type 2 diabetes mellitus. Amid safety concerns raised by regulatory agencies regarding potential associations with suicidal ideation or behavior, real-world data on psychiatric risks are critically needed. This study aims to evaluate the association between tirzepatide and suicidal ideation or attempts compared to other anti-obesity medications in a real-world population.

Methods: A retrospective cohort study using data from the TriNetX US Collaborative Network, covering 66 healthcare organizations from May 2022 to April 2024. A total of 226,060 patients with overweight or obesity, including 29% with type 2 diabetes, were included. Propensity score matching was applied to compare tirzepatide (N=42,600) with non-GLP-1 anti-obesity medications (N=183,460).

Results: After matching, 16,321 pairs were analyzed. The mean age was 48.4 years, and 69.1% were female. Over a median follow-up of 365 days, 17 tirzepatide patients and 33 control patients experienced suicidal ideation or attempts. Tirzepatide was associated with a 48% lower risk of suicide ideation or attempts (aHR: 0.52, 95% CI: 0.28-0.91; P=0.001). Subgroup analyses by BMI, HbA1c, and GFR indicated consistent trends of lower risk. While these findings suggest a potential protective association, the observational nature of this study precludes definitive conclusions regarding causality.

Conclusions: Tirzepatide use was associated with a lower observed risk of suicidal ideation or suicide attempts compared with other anti-obesity medications. Long-term studies are needed to confirm these findings.

Keywords: diabets mellitus; obesity; psychiatry; suicide; tirzepatide.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of this study.
Figure 2
Figure 2
Kaplan-Meier chart evaluating the risk of suicidal ideation or suicide attempts in patients treated with tirzepatide and other anti-obesity medications.
Figure 3
Figure 3
Subgroup analysis of the risk of suicidal ideation and suicide attempts in patients treated with tirzepatide compared with non-GLP-1 receptor agonist anti-obesity medications.
See this image and copyright information in PMC

References

    1. Koliaki C, Dalamaga M, Liatis S. Update on the obesity epidemic: after the sudden rise, is the upward trajectory beginning to flatten? Curr Obes Rep. (2023) 12:514–27. doi: 10.1007/s13679-023-00527-y, PMID: - DOI - PMC - PubMed
    1. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: A systematic review and meta-analysis. JAMA. (2013) 309:71. doi: 10.1001/jama.2012.113905, PMID: - DOI - PMC - PubMed
    1. Apovian CM. Obesity: definition, comorbidities, causes, and burden. Am J Manag Care. (2016) 22:s176–185., PMID: - PubMed
    1. Luppino FS, De Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BW, et al. Overweight, obesity, and depression: A systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry. (2010) 67:220. doi: 10.1001/archgenpsychiatry.2010.2, PMID: - DOI - PubMed
    1. Graham C, Frisco M. The relationship between obesity and suicide ideation among young adults in the United States. SSM - Popul Health. (2022) 18:101106. doi: 10.1016/j.ssmph.2022.101106, PMID: - DOI - PMC - PubMed

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