Large cohort study finds no suicide safety signal for tirzepatide

People taking tirzepatide (sold as Mounjaro and Zepbound) had about half the rate of recorded suicidal ideation or suicide attempts as people taking other weight-loss medications, according to a study published November 16, 2025, in the journal Frontiers in Psychiatry ^[1]. The authors describe the result as the absence of a safety signal for tirzepatide, not evidence that the drug protects against suicide ^[1].

What the study found

Over a median follow-up of 365 days, 17 of 16,321 patients taking tirzepatide had a first recorded episode of suicidal ideation or a suicide attempt, compared with 33 of 16,321 matched patients taking other anti-obesity medications ^[1]. The adjusted hazard ratio was 0.52 (95% confidence interval 0.28–0.91; P=0.001), which the authors describe as a 48% lower risk ^[1]. Based on those counts, that works out to roughly 1 case per 1,000 people in the tirzepatide group and about 2 per 1,000 in the comparison group ^[1].

Subgroup analyses by body mass index, HbA1c and kidney function (GFR) showed consistent trends toward lower risk, the authors wrote ^[1]. They note that these subgroup analyses were exploratory and were not corrected for multiple comparisons ^[1].

How the study was done

The researchers ran a retrospective cohort study using the TriNetX US Collaborative Network, which draws on electronic health records from 66 healthcare organizations, covering May 2022 through April 2024 ^[1]. They started with 226,060 patients who had overweight or obesity, about 29% of them with type 2 diabetes ^[1].

The comparison group took anti-obesity medications that are not GLP-1 drugs: bupropion, naltrexone, orlistat, topiramate, phentermine or setmelanotide ^[1]. Patients with a documented history of suicidal ideation or suicide attempts before the study start were excluded, as were patients who had previously been prescribed another GLP-1 drug ^[1].

After 1-to-1 propensity score matching on factors including age, sex, race, BMI, HbA1c and pre-existing mental health conditions, the analysis included 16,321 pairs ^[1]. The mean age was 48.4 years and about 69% were female ^[1]. The authors report that the two groups were well balanced after matching, with standardized mean differences below 0.1 on all comparisons ^[1].

Limits the authors flagged

Because the study is observational, it cannot show that tirzepatide caused the difference in outcomes; the authors write that the design "precludes definitive conclusions regarding causality" ^[1].

Follow-up was capped at one year per patient, and the authors acknowledge that one year "may be a relatively short period for assessing long-term psychiatric outcomes" ^[1]. Outcomes came from diagnoses recorded during clinical visits, which means they reflect people who sought care rather than everyone who experienced symptoms ^[1]. The matching method can exclude some patients and introduce selection bias, the authors note ^[1]. They also did not run advanced sensitivity analyses such as Bayesian modeling or inverse probability weighting, citing platform constraints and the rarity of the events ^[1].

The study did not compare tirzepatide head-to-head with semaglutide (Ozempic, Wegovy, Rybelsus); the comparison was against non-GLP-1 weight-loss drugs ^[1]. It also does not answer whether the findings apply to people with a prior history of suicidality, because those patients were excluded from the analysis ^[1].

Why it matters for patients

The context for this study is a European Medicines Agency alert about a possible link between GLP-1 receptor agonists and suicidal ideation and behavior ^[1]. The paper notes that randomized trials have not established a psychiatric risk profile for other GLP-1 drugs such as liraglutide and semaglutide, and that observational studies have largely shown no increased suicide risk with their use ^[1]. This analysis is one of the few focused specifically on tirzepatide ^[1].

For patients, the practical reading is narrow: in this large set of medical records, tirzepatide users were not diagnosed with suicidal ideation or attempts more often than users of other weight-loss drugs — they were diagnosed less often ^[1]. The total number of events was small, 50 across roughly 32,600 people, so the estimate is imprecise even though the confidence interval stayed below 1 ^[1]. The study counted diagnoses in records; it did not measure mood symptoms directly, so it cannot say how patients felt ^[1].

What happens next

The authors call for long-term studies to confirm the findings, noting that a one-year window limits what can be concluded about psychiatric outcomes ^[1]. No regulatory action in response to this study is described in the paper, and no timeline for further research has been disclosed ^[1].

If you or someone you know is in crisis, the 988 Suicide and Crisis Lifeline can be reached by calling or texting 988 in the US.