GLP-1 Receptor Agonists Unlikely to Increase Risk of Suicide-Related Events

Individuals receiving glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in randomized controlled trials (RCTs) of adults with diabetes or obesity did not experience an increased incidence of suicide-related adverse events, an analysis finds.¹ While these findings may help alleviate concerns over the drugs’ psychiatric safety, researchers emphasize the importance of ongoing monitoring, especially as the use of GLP-1 RAs continues to grow.

Study finds no significant increase in suicide-related events with glucagon-like peptide-1 receptor agonists in clinical trial. | Image credit: Patrick Bay Damsted - stock.adobe.com

The systemic review is published in JAMA Psychiatry.

“Taken together, these findings may help ease concerns among health care clinicians and patients who are considering these treatments,” wrote the researchers of the study. “Furthermore, for individuals with obesity considering weight loss treatment alternatives who are estimated to be at elevated risk of suicide or self-harm due to psychiatric history or other psychosocial factors, GLP-1 RAs may emerge as a preferred treatment modality over bariatric surgery. At the very least, these data may enter a risk-benefit discussion among patients and clinicians.”

GLP-1 RAs have recently been linked to concerns about a potential increased risk of depression and suicidality.² Assessing this risk is particularly complex due to the bidirectional relationship between obesity and depression, where individuals with obesity are more likely to experience depression, and vice versa. Past safety issues with appetite suppressants, such as the withdrawal of rimonabant in 2008 due to psychiatric adverse effects, underscore the importance of careful monitoring.

In the current study, the researchers aimed to assess the potential association between GLP-1 RAs and the risk of suicidality and self-harm in adults with diabetes or obesity.¹

Data were collected from Medline, Embase, ClinicalTrials.gov, and Cochrane databases up to August 29, 2023. Eligible studies included RCTs lasting 6 months or longer that compared GLP-1 RAs with placebo for the treatment of diabetes or obesity. The primary outcome was a pooled estimate of the incidence of completed or attempted suicide, suicidal ideation, or self-harm.

Among 144 RCTs identified, 27 recorded suicide and self-harm-related events, including 32,357 individuals receiving GLP-1 RAs and 27,046 receiving placebo, with follow-up totaling 74,740 and 68,095 person-years, respectively. The incidence of events was extremely low in both groups, at 0.044 per 100 person-years for GLP-1 RA users and 0.040 per 100 person-years for placebo, with no statistically significant difference (rate ratio [RR], 0.76; 95% CI, 0.48-1.21; P = .24). Subgroup analyses found no evidence of differing outcomes based on diabetes status or the specific GLP-1 RA used. While 5 studies were noted to have a potential risk of bias due to the loss of more than 5% of participants to follow-up, overall, the included trials were deemed to have low heterogeneity and minimal risk of bias.

However, the researchers acknowledged some limitations, including the low rates of psychiatric outcome tracking and variability in how suicidal ideation and self-harm events were defined and recorded, which could have influenced the pooled estimates. While no significant differences were observed between liraglutide and other GLP-1 RAs, subgroup analyses for specific agents or varied doses were not possible, limiting the ability to detect potential differences. Additionally, the intensive medical monitoring in RCTs may have reduced the risk of suicide-related events compared with real-world settings.

Despite these limitations, the researchers believe the study finds no significant risk of suicide-related events among this patient population in a RCT setting.

“In conclusion, our comprehensive systematic review and meta-analysis does not support an association between GLP-1 RA treatment of adults with diabetes, overweight, or obesity and increased risk of adverse psychiatric events, inclusive of suicide completion or attempt, suicidal ideation, and self-harm,” wrote the researchers.

References

1. 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

2. Salvo F, Faillie J. GLP-1 receptor agonists and suicidality—caution is needed. JAMA Netw Open. 2024;7(8):e2423335. doi:10.1001/jamanetworkopen.2024.23335