Clarification Needed on Semaglutide-Linked Suicidal Ideation Alert

Researchers look into the possible connection between suicidal or self-injurious adverse drug reactions and the obesity medications semaglutide and liraglutide in a recent study that was published in JAMA Network Open.

GLP-1 RAs’ effects on mental health
Because they help people lose weight, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which were first created for type 2 diabetes (T2D), have gained more attention as a result of the global obesity crisis. There are shortages of GLP-1 RAs worldwide as a result of their increased use beyond their original intended use, such as liraglutide and semaglutide.

There have been questions raised concerning the safety of GLP-1 RAs, specifically the possibility of suicidal thoughts. No conclusive link has been found between these medications and the risk of suicide, despite regulatory bodies such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) starting investigations into these concerns.

The objective of this study was to examine the global incidence of suicidal and self-injurious adverse drug reactions (ADRs) linked to the use of liraglutide or semaglutide. The World Health Organization (WHO) database of individual case safety reports (ICSRs) was utilized to facilitate this investigation.

About the Study

ICSRs from over 28 million records spanning 140 countries are included in the largest global pharmacovigilance database, WHO Vigibase, from which the current case-control study was started as a disproportionality analysis. Since the data were anonymised, the study complied with ethical standards and did not require patient consent.

A thorough database search was done to find reports about these medications that addressed ADRs categorized as “suicide/self-injury.” Reports on semaglutide were gathered from July 2011 to August 2023, whereas reports on liraglutide were acquired from November 2000 to August 2023.

The reporting odds ratio (ROR) and Bayesian information component (IC) were computed using proportionality analysis to ascertain whether these pharmaceuticals were linked to an increased risk of these adverse drug reactions (ADRs) in comparison to other medications. Sensitivity analyses were also carried out to compare the results with other medications used for treating obesity and type 2 diabetes, such as dapagliflozin, metformin, and orlistat, and to take into consideration confounding factors, such as the concurrent use of antidepressants and benzodiazepines.

In conclusion
The results of the study add to the continuing evaluations of the safety of semaglutide and liraglutide, especially in light of their possible influence on suicidal tendencies.

Social media users’ personal reports of using semaglutide are becoming more and more popular, which could lead to off-label usage and raise dangers to the public’s health, including the illegal trade in counterfeit semaglutide. Given that using off-label semaglutide carries a risk of suicidal thoughts, federal authorities ought to think about notifying the public about these hazards.

For more information: Disproportionality Analysis From World Health Organization Data on Semaglutide, Liraglutide, and Suicidality. JAMA Network Open, doi:10.1001/jamanetworkopen.2024.23385.