GLP-1 receptor agonist use poses no risk of suicidality, self-harm

Users of glucagon-like peptide-1 (GLP-1) receptor agonists, most of whom have type 2 diabetes, are not at increased risk of suicide death, self-harm, or incident depression and anxiety-related disorders, as shown in a study.

Researchers conducted an active-comparator new-user cohort study and used nationwide register data from Sweden and Denmark. A total of 124,517 adults who initiated a GLP-1 receptor agonist and 174,036 adults (mean age 60 years, 45 percent women) who initiated a sodium-glucose cotransporter-2 (SGLT2) inhibitor were identified and included in the study.

Suicide death, the primary outcome, was recorded in the cause of death registers. Secondary outcomes included the composite of suicide death and nonfatal self-harm, as well as the composite of incident depression and anxiety-related disorders. Propensity score weighting was applied, with risk estimates calculated separately in the two countries and pooled in a meta-analysis.

Over a mean follow-up of 2.5 years, 77 suicide deaths were documented among GLP-1 receptor agonist users and 71 suicide deaths among SGLT2 inhibitor users. These numbers translated to weighted incidence rates of 0.23 and 0.18 events per 1,000 person-years (hazard ratio [HR], 1.25, 95 percent confidence interval [CI], 0.83–1.88). The absolute difference was 0.05 (95 percent CI, −0.03 to 0.16) events per 1,000 person-years.

Compared with SGLT2 inhibitor users, GLP-1 receptor agonist users also had a slightly lower risk of the composite of suicide death and nonfatal self-harm (HR, 0.83, 95 percent CI, 0.70–0.97). GLP-1 receptor agonist use showed no association with the composite of incident depression and anxiety-related disorders (HR, 1.01, 95 percent CI, 0.97–1.06).

The findings show that the absolute risks of suicide death in broad groups of patients using GLP-1 receptor agonists are low and any potential risk increase would be small.