Risk of Psychiatric Worsening With GLP ‐1 Receptor Agonist Use in Patients With Type 2 Diabetes and Treated Depression

ABSTRACT Aims To compare 1‐year psychiatric outcomes after GLP‐1 receptor agonist (GLP‐1 RA) versus sodium‐glucose cotransporter‐2 inhibitor (SGLT2i) initiation in patients with type 2 diabetes and treated depression. Materials and Methods We conducted a retrospective active‐comparator, new‐user cohort study using electronic health records from the TriNetX network. Patients with type 2 diabetes, depression and antidepressant treatment within 6 months before index were included. After 1:1 propensity score matching, outcomes were compared using Cox proportional hazards models. Primary outcomes were suicidality and antipsychotic use. All‐cause mortality was a secondary outcome. Results After propensity score matching, 34 761 patients were included in each group. GLP‐1 RA initiation was not associated with a higher risk of suicidality than SGLT2i initiation (hazard ratio HR 0.88, 95% CI 0.74–1.05). GLP‐1 RA initiation was associated with a lower risk of antipsychotic use (HR 0.86, 95% CI 0.82–0.90; absolute risk difference −1.4%) and lower all‐cause mortality (HR 0.64, 95% CI 0.58–0.71). Findings were consistent across sensitivity analyses. Conclusions In patients with type 2 diabetes and treated depression, we did not detect increased short‐term documented suicidality after GLP‐1 RA initiation compared with SGLT2i initiation and observed less subsequent treatment intensification. These observational findings suggest that treated depression alone should not lead to routine avoidance of GLP‐1 RAs in this population.