Use of Glucagon-Like Peptide 1 Receptor Agonists and the Associated Risk of Hospitalisation in Bipolar Disorder, From a Nationwide Cohort, 2009-2024.

INTRODUCTION: Diabetes, obesity and bipolar disorder often co-occur and may have shared pathophysiology. Glucagon-like peptide 1 receptor agonists (GLP-1RA) treat diabetes and obesity but their impact on bipolar disorder is unknown. In this era of stagnated pharmacotherapy, we examined psychiatric hospitalisation and absence from work due to sick leave as potential measures of relapse in people diagnosed with bipolar disorder who were also prescribed antidiabetic medications, including GLP-1RA. METHODS: The study cohort was derived from the National Swedish Registers and included all people with a diagnosis of bipolar disorder who used any antidiabetic medication, between the years 2009 and 2024. GLP-1RA individually and as a group were compared with non-use of GLP-1RA, and directly with other second-line antidiabetic medications. A within-individual design was utilised for all comparisons to reduce confounding. The main outcome was psychiatric hospitalisation for any reason, with secondary outcomes being psychiatric hospitalisation after a relapse of bipolar disorder, and sick leave due to psychiatric reasons. Within-individual stratified Cox models with adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were used. RESULTS: 14,694 people were included in the study, of whom 5200 used GLP-1RA. Semaglutide was associated with a 21% (aHR 0.79, 95% CI 0.69-0.91) lower risk of psychiatric hospitalisation compared with non-use of GLP-1RA in that same individual. Liraglutide and dulaglutide were not specifically associated with a lower hospitalisation risk. Semaglutide was also linked to a 17% (aHR 0.83, 95% CI 0.69-0.99) lower risk of relapse of bipolar disorder. Absences from work due to sick leave were not significantly associated with the specific antidiabetic medications studied. CONCLUSION: In people with both bipolar disorder and diabetes and/or obesity, the use of semaglutide was linked to lower rates of psychiatric hospitalisation compared with time periods when GLP-1RA were not used by that individual. Liraglutide and dulaglutide were not associated with reduced psychiatric hospitalisation, implying this is not a class effect. This finding with semaglutide should be further tested in a randomised controlled trial.