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

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.