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Meta-Analysis Confirms the Unlikelihood of GLP-1 RA Raising Suicidal Risk
A meta-analysis of 27 trials found no increased risk of suicide or self-harm with GLP-1 RAs, supporting their safety for diabetes and obesity management.
Yet another study confirmed that peptide-1 receptor agonist (GLP-1 RA) is unlikely to increase suicide-related adverse events.1
In July 2024, a study was published that reported GLP-1 RAs do not increase the risk for suicidal thoughts or behaviors.2 People have worried that GLP-1 RAs raise suicidal thoughts; even the US Food and Drug Administration (FDA) got involved, evaluating reports of suicidal thoughts or actions in patients taking GLP-1 RAs. The FDA announced on January 11, 2024, that the preliminary evaluation and review of clinical trials did not show evidence that these medications lead to suicidal thoughts or actions.
Still, investigators wanted to conduct further research on this, to see whether GLP-1 RA for the management of diabetes or obesity was associated with the risk of suicidality and self-harm.1
“In this first meta-analysis focused solely on suicide and self-harm within RCTs of GLP-1 RAs among adults with diabetes or obesity, we found that that there is unlikely to be an increase in the very low incidence of these events (that appear similar to rates within the general population) among individuals receiving GLP-1 RAs within the context of RCTs,” wrote investigators, led by Pouya Ebrahimi, MD, from Tehran Heart Center, Cardiovascular Diseases Research Institute at Tehran University of Medical Sciences in Iran. “These findings help shape our understanding of the safety profile of GLP-1 RAs, aligning with the growing body of observational data that does not suggest an increased risk of suicide and/or self-harm events in association with GLP-1 RA use.”
The team conducted a systematic review and meta-analysis of 144 studies; MEDLINE, Embase, ClinicalTrial.gov, and Cochrane databases were searched from inception to August 29, 2023. Investigators identified randomized clinical trials (RCTs) that lasted ≥ 6 months and compared GLP-1 RA vs placebo for the management of diabetes or obesity. In total, 27 trials met inclusion criteria and recorded events of suicide or self-harm; this included 32,357 participants receiving GLP-RAs and 27046 receiving a placebo, with the mean age 59.5 years and 44% females.
In the GLP-1 RAs group, there were 33 occurrences of death by suicide, suicide attempts, suicidal ideation, or self-harm (unadjusted incidence rate, 0.044 per 100 person-years; weighted incidence rate, 0.051; 95% confidence interval [CI], 0.040 – 0.062 per 100-person years). The placebo group had 27 deaths (unadjusted incidence rate, 0.040 per 100 person-years; weighted incidence rate, 0.052; 95% CI, 0.037 – 0.068 per 100 person-years). The findings indicate that suicide or suicide harm incidence was low in both groups.
Additionally, the GLP-1 RA and placebo group had no statistically significant difference in suicide or self-harm (rate ratio, 0.76; 95% confidence interval [CI], 0.48 – 1.21; P = .24). Subgroup analyzes also showed no differences in suicide or self-harm incidences based on diabetes status (P = .98) or the type of GLP-1 RA used (P = .89).
Investigators did note that 5 studies were considered at risk of bias since they lost > 5% of participants to follow-up. However, other than that, studies were found to be heterogeneous and not at a high risk of bias.
“Taken together, these findings may help ease concerns among health care clinicians and patients who are considering these treatments,” investigators wrote. “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.”
References
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
Derman, C. GLP-1RAs Not Linked to Increased Risk for Suicidal Thoughts. HCPLive. July 16, 2024. https://www.hcplive.com/view/glp-1ras-not-linked-to-increased-risk-for-suicidal-thoughts. Accessed March 26, 2025.
