Do GLP-1 receptor agonists increase the risk of suicide in patients?

By Vijay Kumar MalesuReviewed by Lily Ramsey, LLMJan 6 2025

Nationwide research reassures the short-term psychiatric safety of GLP-1 RAs, with no heightened risk observed in patients with psychiatric disorders or obesity.

Study: Suicide and suicide attempt in users of GLP-1 receptor agonists: a nationwide case-time-control study. Image Credit: KK Stock/Shutterstock.com

In a recent study published in the eClinicalMedicine, a group of researchers evaluated the association between Glucagon-like peptide-1 receptor agonists (GLP-1 RA) use and the risk of suicide or suicide attempt, accounting for psychiatric history and obesity.

Background

GLP-1 RAs are used for treating type 2 diabetes and weight loss by regulating insulin secretion, appetite, and gastric emptying. Given the withdrawal of past appetite suppressants due to suicidality risks, concerns about GLP-1 RAs' psychiatric safety persist.

.While clinical trials report no significant psychiatric risks, their exclusion of patients with mental health disorders limits generalizability. Observational studies show inconsistent results and pharmacovigilance reports raise further questions.

Considering the increasing use of GLP-1 RAs in obesity and among patients on psychotropic drugs, further research is essential to evaluate psychiatric safety in high-risk populations.

About the study

A nationwide study using the French National Health Data System (SNDS) (2013-2021) evaluated the short-term association between GLP-1 RA and suicidal behaviors.

The SNDS contains anonymized sociodemographic and medical data, including outpatient services, hospital discharges, drug dispensing, and causes of death. Ethics approval and informed consent were waived under French regulations.

A case-time-control (CTC) design, extending the case-crossover approach, was used to address confounding factors, exposure-trend bias, and persistent user bias. Suicidal behaviors, defined as hospitalization for suicide attempts or death by suicide, were identified using International Classification of Diseases, 10th Revision (ICD-10) codes.

GLP-1 RA exposure (exenatide, dulaglutide, liraglutide, semaglutide) was assessed over 30-day risk and reference periods, separated by a 60-day washout.

Cases included adults hospitalized for suicide attempts or suicides with at least one GLP-1 RA dispensing in the preceding 180 days, matched with time-controls by sex, age, psychiatric history, and obesity.

Conditional logistic regression models estimated odds ratios, adjusting for time-varying confounders. Subgroup and sensitivity analyses explored variations by psychiatric history, obesity, sex, age, and exposure duration.

A negative control analysis with Dipeptidyl Peptidase-4 (DPP-4) inhibitors assessed bias. This study was part of the Drugs-Safe® program funded by the French Medicines Agency (ANSM), which had no role in study execution or interpretation.

Study results Between 2013 and 2021, 1,102 individuals who attempted or completed suicide and had been dispensed GLP-1 RA during the 180 days prior to the event were identified and matched to 5494 time controls. The mean age of cases was 57.4 years (SD 11.2), with 44.6% male.

Notably, 67.7% of cases had a recent psychiatric history, including antidepressant use in 59.2% and antipsychotic use in 21.6%. Obesity was present in 51.3% of cases. Other common comorbidities included atherosclerotic cardiovascular disease (21.4%) and sleep apnea (27.8%). Time controls were similar in age, sex, psychiatric history, and obesity, ensuring comparability.

GLP-1 RA use was not associated with an increased risk of suicidal behaviors after adjusting for exposure trends and covariates. The adjusted odds ratio (OR) was 0.62 (95% CI, 0.51–0.75), indicating a negative association.

This finding remained consistent across subgroups stratified by psychiatric history, obesity, sex, and age. Similar results were observed in sensitivity analyses with alternative risk and reference periods and negative control analyses using DPP-4 inhibitors.

DPP-4 inhibitor cases were generally older, more often male, and had lower rates of psychiatric disorders and obesity than GLP-1 RA cases. However, the association between DPP-4 inhibitor use and suicidal behaviors mirrored that of GLP-1 RA, further supporting the accuracy of the findings.

Stratified analyses revealed no significant differences in the association based on psychiatric history or obesity, and consistent results were observed when stratified by sex or age.

Sensitivity analyses using shorter (15 days) and longer (45 days) risk and reference periods confirmed the stability of the findings.

These results suggest that GLP-1 RA use does not increase the risk of suicidal behaviors, even in populations with high-risk characteristics, such as psychiatric disorders or obesity.

Conclusions

To summarize, this study confirms the short-term psychiatric safety of GLP-1 RA, showing a negative association with suicidal behaviors (adjusted OR, 0.62; 95% CI, 0.51–0.75), consistent with findings for DPP-4 inhibitors.

Results were accurate across subgroups, including patients with obesity or psychiatric histories. While reduced healthcare access before suicide attempts may explain this association, long-term risks remain unexplored.