In a large real‑world study of people with overweight or obesity, those who took tirzepatide had about half the risk of reporting suicidal thoughts or attempts compared with people using other weight‑loss drugs. The data come from electronic health records, and while the study can’t prove cause and effect, it suggests tirzepatide may be safer for mental health than some alternatives.

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. 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). 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. 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.