Adults with schizophrenia and Type 2 diabetes who started a glucagon-like peptide-1 receptor agonist were less likely to be hospitalized or seen in the emergency department for psychiatric reasons than peers who started a dipeptidyl peptidase-4 inhibitor, a sodium-glucose cotransporter-2 inhibitor or none of the three drug classes, according to a study published in The Lancet Psychiatry.
The results point to a possible psychiatric upside to GLP-1 therapy beyond blood sugar and weight control, though the study’s observational design means it cannot show the drugs caused the lower risk.
A research team led by Deakin University in Geelong, Australia, used EHR data from the U.S. NeuroBlu Data repository to build a cohort of 70,257 adults diagnosed with both schizophrenia and Type 2 diabetes between 2018 and 2025. Patients who began GLP-1 therapy were compared with those who began DPP-4 inhibitors or SGLT2 inhibitors and with those who started none of the three. Follow-up lasted up to two years. Researchers applied statistical weighting to balance the groups on demographic, clinical and medication factors.
Here are five things to know:
1. GLP-1 initiators had a lower risk of psychiatric hospitalization than non-initiators (hazard ratio, 0.76). Their hospitalization risk was also lower than that of patients who started DPP-4 inhibitors (HR, 0.82) or SGLT2 inhibitors (HR, 0.83).
2. GLP-1 initiators also had a lower risk of a psychiatric emergency department visit than non-initiators (HR, 0.71). Their risk was also lower than that of DPP-4 inhibitor initiators (HR, 0.87) and SGLT2 inhibitor initiators (HR, 0.80).
3. GLP-1 initiators made up 12.9% of the cohort. Of the 70,257 adults studied, 9,093 initiated a GLP-1 receptor agonist, 5,328 initiated an SGLT2 inhibitor and 4,968 initiated a DPP-4 inhibitor. The other 50,868 started none of the three.
4. Lower risk was most evident in certain patient groups. The link was clearest among men, adults younger than 55 and patients taking antipsychotics. Findings were less consistent for adults 55 and older and across comorbidity and weight groups. No consistent association appeared among patients not on antipsychotics or those in the lowest weight quartile.
5. The researchers said GLP-1 drugs should not be viewed as psychiatric treatments. They noted that residual confounding and selection bias limit how widely the results apply. Fewer psychiatric acute care encounters could be a secondary benefit when GLP-1s are prescribed for metabolic needs, the researchers said, but randomized and mechanistic studies are needed to determine whether the drugs directly improve psychiatric outcomes.
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