Acta Psychiatrica ScandinavicaUse of Glucagon-Like Peptide 1 Receptor Agonists and the Associated Risk of Hospitalisation in Bipolar Disorder, From a Nationwide Cohort, 2009–2024

ℹ️ Observational Association Only Evidence

Researchers used Swedish national registers to examine psychiatric outcomes among 14,694 people with bipolar disorder who received antidiabetic medications from 2009 through 2024. Within-individual analyses compared periods of GLP-1 receptor agonist exposure with non-use periods in the same person. Semaglutide was associated with lower risks of psychiatric hospitalization and hospitalization for bipolar relapse. Liraglutide and dulaglutide did not demonstrate similar associations, arguing against interpreting the finding as a class effect. The observational design did not establish causality.

Clinical Considerations

• Semaglutide use was associated with a 21% lower psychiatric hospitalization risk versus periods without GLP-1 receptor agonist use.
• Hospitalization specifically attributed to bipolar relapse was 17% less likely during semaglutide exposure periods.
• The association persisted after excluding the first 30 exposure days and hospitalizations primarily related to substance use disorders.
• Liraglutide and dulaglutide were not significantly associated with lower hospitalization risks, although their smaller samples reduced statistical power.
• GLP-1 receptor agonist exposure was not significantly associated with psychiatric sick leave, suggesting no consistent functional-outcome signal.
• The study lacked individual symptom severity, weight, body mass index, and glycemic measurements, leaving important time-varying confounding unresolved.

Practice Applications

• Recognize that semaglutide is not an established treatment for bipolar disorder.
• Interpret the hospitalization association separately from the approved metabolic indications for GLP-1 receptor agonists.
• Avoid generalizing the semaglutide finding across the entire GLP-1 receptor agonist class.
• Consider psychiatric outcomes when following patients receiving semaglutide for diabetes or obesity.
• Monitor randomized trials evaluating whether the observed association reflects a direct psychiatric effect.