Systematic Review of Suicide, Self-Harm Potentiality in GLP-1 RA Trials

In a systematic review and meta-analysis of 144 studies, researchers aimed to answer whether glucagon-like peptide 1 receptor agonist (GLP-1 RA) for the treatment of obesity or diabetes is associated with risk for suicidal and/or self-harm behavior and ideation. The study was published in JAMA Psychiatry.

The researchers identified randomized clinical trials lasting more than 6 months in MedLine, Embase, ClinicalTrials.gov, and Cochrane databases. The trials compared GLP-1 RAs to placebo for the treatment of diabetes or obesity.

The main outcomes and measures were pooled incidence of completed or attempted suicide, occurrences of suicidal ideation, or self-harm. Out of 144 randomized controlled trials, 27 systematically tracked suicide and/or self-harm events.

The 27 studies included 32,357 individuals treated with GLP-1 RAs and 27,046 who received placebo. The incidence of suicidal or self-harm events was very low for both groups: 0.044 per 100 person-years for the GLP-1 RA group and 0.040 per 100 person-years for the placebo group, with no statistically significant difference observed (rate ratio, 0.76; 95% CI, 0.48-1.21; P=0.24). Subgroup analysis showed no outcome variation based on diabetes status or the specific GLP-1 RA used.

“There is unlikely to be an increase in the very low incidence of suicide-related adverse events among individuals receiving GLP-1 RAs within the context of RCTs. While these findings may further ease concerns about these adverse effects, continued monitoring is warranted to identify particular patients who may be at risk as extended use of GLP-1 RAs expands,” the researchers concluded.

Reference

Ebrahimi P, Batlle JC, Ayati A, et al. Suicide and self-harm events with GLP-1 receptor agonists in adults with diabetes or obesity: a systematic review and meta-analysis. JAMA Psychiatry. Published online March 19, 2025. doi:10.1001/jamapsychiatry.2025.0091