AMONG adults with schizophrenia and Type 2 diabetes, starting glucagon-like peptide-1 (GLP-1) receptor agonists has been associated with a lower risk of psychiatric hospitalisation and emergency department presentation than non-initiation or other glucose-lowering treatments, according to a large US analysis.
Many people with schizophrenia have persistent psychotic symptoms despite antipsychotic treatment, and the disorder remains associated with a disproportionately high burden of metabolic dysregulation. Whether GLP-1s offer psychiatric benefit alongside their metabolic effects in schizophrenia was unknown, as psychiatric outcomes had rarely been prespecified in antihyperglycaemic trials and no study had compared GLP-1s with active glucose-lowering comparators for acute psychiatric service use.
Researchers conducted an observational cohort study using electronic health record data from the US NeuroBlu Data repository, including 70,257 adults with schizophrenia and Type 2 diabetes (mean age 53.1 years; standard deviation: 12.32; 33,882 women, 48.2%). From 2018 to 2025, 9,093 participants (12.9%) initiated GLP-1s, 4,968 (7.1%) initiated dipeptidyl peptidase-4 (DPP-4) inhibitors, 5,328 (7.6%) initiated sodium-glucose cotransporter-2 (SGLT2) inhibitors and 50,868 (72.4%) were non-initiators. Participants were followed for up to 2 years.
Initiating GLP-1s was associated with a lower risk of psychiatric hospitalisation than non-initiation (weighted hazard ratio [HR]: 0.76; 95% CI: 0.71–0.82), DPP-4 inhibitor initiation (HR: 0.82; 95% CI: 0.75–0.90) and SGLT2 inhibitor initiation (HR: 0.83; 95% CI: 0.78–0.88). Initiating GLP-1s was also associated with a lower risk of emergency department presentation than non-initiation (HR: 0.71; 95% CI: 0.65–0.77), DPP-4 inhibitor initiation (HR: 0.87; 95% CI: 0.80–0.95) and SGLT2 inhibitor initiation (HR: 0.80; 95% CI: 0.73–0.88). Associations were most evident in adults younger than 55 years, men and antipsychotic users, but were not observed across comparators in adults aged 55 years or older.
The findings suggest that lower psychiatric acute-care use could be a favourable secondary benefit when GLP-1s are clinically indicated for metabolic management in schizophrenia, although residual confounding and selection bias may limit generalisability.
Reference
Davoodian N et al. GLP-1 receptor agonist initiation and risk of psychiatric hospitalisation and emergency department presentation in adults with schizophrenia and type 2 diabetes in the USA: an observational cohort study using electronic health records data. Lancet Psychiatry. 2026;13(11):931-42.
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