Background: Incretin therapies have shown promise in managing antipsychotic-associated weight gain and psychological benefits in individuals with mental health disorders. In populations at high risk for suicidal behaviors, it is crucial to understand how these therapies affect risk of suicidality or self-harm. Aims: This study investigates the effect of incretin therapy on suicidality or self-harm in individuals with severe mental disorders (SMDs). Methods: A retrospective cohort study was developed using the TriNetX Research Network, a federated database collating de-identified data from electronic health records. Adult individuals diagnosed with a psychotic disorder and treated with an antipsychotic were included. Cohorts were differentiated based on concomitant incretin therapy and balanced using 1:1 propensity score matching. Psychiatric outcomes were compared during the 5 years following the index date. Results: After matching, each cohort consisted of 21,984 individuals. Receipt of incretin therapy was associated with reduced relative risk (RR) for suicidal ideation (RR: 0.48; 95% CI: 0.45–0.51; p < 0.0001), suicide attempts (RR: 0.64; 95% CI: 0.52–0.78; p < 0.0001), and self-harm (RR: 0.61; 95% CI: 0.56–0.67; p < 0.0001) compared to the no treatment group. Additionally, individuals receiving incretin therapy had lower risk for all-cause mortality (RR: 0.50; 95% CI: 0.46–0.53; p < 0.0001), overdose (RR: 0.57; 95% CI: 0.49–0.65; p < 0.0001), and substance use disorders (RR: 0.76; 95% CI: 0.74–0.77; p < 0.0001). Conclusions: Our findings suggest incretin therapies may have protective effects against various psychiatric and behavioral risks in individuals with SMD.
Kalamaras et al. (2026) studied this question.