A recent study published in eClinicalMedicine investigated the potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the risk of suicide or suicide attempts. The nationwide research, utilizing data from the French National Health Data System (SNDS), found no evidence of increased short-term psychiatric risk associated with GLP-1 RA use, even among patients with psychiatric disorders or obesity.
Background and Concerns
GLP-1 RAs are commonly prescribed for type 2 diabetes and weight loss due to their effects on insulin secretion, appetite regulation, and gastric emptying. However, concerns have been raised regarding their psychiatric safety, particularly given the history of appetite suppressants being withdrawn due to suicidality risks. While clinical trials have generally not indicated significant psychiatric risks, they often exclude patients with pre-existing mental health conditions, limiting the generalizability of their findings.
Study Design and Methodology
The study employed a case-time-control (CTC) design using data from the SNDS between 2013 and 2021. This approach allowed researchers to mitigate confounding factors and biases. The study identified 1,102 individuals who had attempted or completed suicide and had been dispensed GLP-1 RA within 180 days prior to the event. These cases were matched with 5,494 time controls based on sex, age, psychiatric history, and obesity.
GLP-1 RA exposure, including exenatide, dulaglutide, liraglutide, and semaglutide, was assessed over 30-day risk and reference periods. Conditional logistic regression models were used to estimate odds ratios, adjusting for time-varying confounders. Subgroup and sensitivity analyses were conducted to explore variations based on psychiatric history, obesity, sex, age, and exposure duration. A negative control analysis using Dipeptidyl Peptidase-4 (DPP-4) inhibitors was also performed to assess potential bias.
Key Findings
The study found that GLP-1 RA use was not associated with an increased risk of suicidal behaviors. The adjusted odds ratio (OR) was 0.62 (95% CI, 0.51–0.75), indicating a negative association. This finding remained consistent across various subgroups, including those with psychiatric history, obesity, and different age and sex categories. Sensitivity analyses with varying risk and reference periods, as well as the negative control analysis using DPP-4 inhibitors, further supported these results.
Implications and Interpretation
The results of this study suggest that GLP-1 RA use does not elevate the risk of suicidal behaviors, even in populations with high-risk characteristics such as psychiatric disorders or obesity. The researchers noted that reduced healthcare access before suicide attempts might contribute to the observed negative association. However, they also emphasized that long-term risks remain to be investigated.
Study Limitations
While the study provides valuable insights, it is essential to acknowledge its limitations. The observational nature of the study means that causality cannot be definitively established. Additionally, the study focused on short-term risks, and further research is needed to evaluate the long-term psychiatric safety of GLP-1 RAs.
