A recent nationwide study published in eClinicalMedicine evaluated the potential link between the use of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidal behaviors, focusing on patients with psychiatric histories and obesity. The study found no significant increase in the risk of suicide or suicide attempts among users of GLP-1 RAs.
Background
GLP-1 RAs are commonly prescribed for the management of type 2 diabetes and obesity, as they help regulate insulin secretion, appetite, and gastric emptying. Despite their widespread use, concerns about the psychiatric safety of GLP-1 RAs persist, particularly due to the history of appetite suppressants being withdrawn from the market due to associated suicidality risks.
While clinical trials generally report no significant psychiatric risks, they often exclude patients with mental health disorders, limiting the broader applicability of the findings. Observational studies have shown inconsistent results, and pharmacovigilance reports have raised further concerns.
Given the rising use of GLP-1 RAs, particularly in individuals taking psychotropic medications, the study aimed to examine the psychiatric safety of these drugs, especially in high-risk populations.
Study Design
The study utilized data from the French National Health Data System (SNDS) for the period 2013-2021, evaluating the short-term association between GLP-1 RA use and suicidal behaviors. The study employed a case-time-control (CTC) design to address confounding factors and potential biases.
Researchers identified 1,102 individuals who had attempted or completed suicide and had been dispensed GLP-1 RA within 180 days before the event. These cases were compared with 5,494 matched controls based on sex, age, psychiatric history, and obesity.
Results
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 between GLP-1 RA use and suicidality. This result remained consistent across various subgroups, including those with psychiatric histories, obesity, and varying age and sex.
Furthermore, sensitivity analyses using alternative risk and reference periods confirmed the stability of the findings. A negative control analysis involving Dipeptidyl Peptidase-4 (DPP-4) inhibitors, another class of diabetes medications, produced similar results, supporting the reliability of the study’s conclusions.
Conclusions
The study concludes that GLP-1 RAs do not appear to increase the risk of suicide or suicide attempts, even in high-risk populations such as those with psychiatric disorders or obesity. These findings suggest the short-term psychiatric safety of GLP-1 RAs, which were consistent with the results observed for DPP-4 inhibitors.
However, the study’s authors note that while the findings provide reassurance for short-term use, the long-term psychiatric risks of GLP-1 RAs remain unexplored and warrant further investigation. The study emphasizes the importance of continued research into the psychiatric safety of GLP-1 RAs, particularly in patients with pre-existing mental health conditions.
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