GLP-1 RAs Unlikely to Increase Suicide Risk

TOPLINE:

A meta-analysis of randomized controlled trials involving over 59,000 patients with diabetes or obesity showed no statistically significant difference in the risk for suicide between those treated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and placebo.

METHODOLOGY:

• Initial reports of increased suicidality in GLP-1 RA users compared with the general population raised concerns about the risk for this rare but serious adverse event, given the rising popularity of these medications.
• Researchers conducted a systematic review and meta-analysis of randomized, placebo-controlled trials lasting 6 or more months to assess the risk for suicides, suicide attempts, suicidal thoughts, and self-harm in patients treated with GLP-1 RAs for diabetes or obesity.
• Data collection involved systematic searches of MEDLINE, Embase, ClinicalTrials.gov, and Cochrane databases, with two independent reviewers screening all search-identified studies and extracting data using accepted guidelines.

TAKEAWAY:

• Researchers identified 27 clinical trials encompassing 32,357 participants receiving GLP-1 RAs and 27,046 receiving placebo who were followed up for 142,835 person-years; the mean age was 59.5 years, and 44.0% of analyzed participants were women.
• In addition, they identified four other randomized controlled trials analyzing the risk for suicidality and self-harm with GLP-1 RAs vs dipeptidyl peptidase-4 (DPP-4) inhibitors.
• Overall, 33 cases of death by suicide, suicide attempts, suicidal thoughts, or self-harm were reported in the meta-analysis of 27 trials.
• The incidence of events was very low in both GLP-1 RA and placebo groups (0.044 and 0.040, respectively, per 100 person-years), with no statistically significant difference between the groups (P = .24); moreover, no difference was observed between the effect of GLP-1 RAs and DPP-4 inhibitors on suicide or self-harm adverse events in the meta-analysis of four trials.
• Subgroup analyses revealed no differences in outcomes based on the presence or absence of diabetes or specific GLP-1 RA medication used.
• Five of 31 studies showed a potential risk for bias due to the loss of more than 5% of participants to follow-up; however, the remaining studies demonstrated low heterogeneity and bias risk.

IN PRACTICE:

“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 authors wrote.

SOURCE:

This study was led by Pouya Ebrahimi, MD, Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran, and Juan Carlos Batlle, MD, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut. It was published online on March 19, 2025, in JAMA Psychiatry.

LIMITATIONS: 

Nearly 80% of qualifying studies did not systematically record suicide-related events, potentially excluding more than 60,000 additional participants from the analysis. More than one third of studies that recorded these events excluded participants with a history of suicide attempts or psychiatric disorders, limiting generalizability to these populations. Subgroup analyses of specific GLP-1 RAs and varying doses of agents were not possible, although studies on obesity typically used higher doses.

DISCLOSURES:

No sources of funding were reported in this study. One author reported serving as a consultant for Novo Nordisk outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.