GLP-1 receptor agonists and risk of suicide or suicide attempts – A nationwide cohort and self-controlled case series study

Abstract The European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) have raised concerns about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicide or suicide attempts. We conducted two new-user, active comparator cohort studies. The GLP1-RAs vs sodium-glucose cotransporter-2 (SGLT-2) inhibitors cohort included new users of GLP-1 RAs ( n  =  83,464 ) or SGLT-2 inhibitors ( n  =  78,366 ), and the GLP1-RAs vs dipeptidyl peptidase-4 (DPP-4) inhibitors cohort included new users of GLP-1 RAs ( n  =  108,322 ) or DPP-4 inhibitors ( n  =  55,411 ). We also employed a self-controlled case series design to compare suicide, or suicide attempts before and after GLP-1 RA treatment initiation across three time periods. In the cohort analyses patients who initiated GLP-1 RAs did not differ in the hazard ratio (HR) for suicide or suicide attempts from SGLT-2 inhibitor users (HR: 0.93; 95% CI: 0.57–1.52), and GLP-1 RA users had a lower risk of suicide or suicide attempts compared with DPP-4 inhibitor users (HR: 0.58; 95% CI: 0.37–0.91). In the self-controlled case series design, use of GLP-1 RAs was associated with a lower incidence rate ratio (IRR) of suicide or suicide attempts one year after treatment initiation (IRR: 0.45; 95% CI: 0.10–0.50) and 13–24 months after treatment initiation compared with pretreatment. This study showed that use of GLP-1 RAs was not associated with increased incidence of suicide or suicide attempts in either the active comparator new-user design or in the self-controlled case series design.