Exploration of the potential association between GLP-1 receptor agonists and suicidal or self-injurious behaviors: a pharmacovigilance study based on the FDA Adverse Event Reporting System database

Abstract

Background Establishing whether there is a potential relationship between glucagon-like peptide 1 receptor agonists (GLP-1RAs) and suicidal or self-injurious behaviors (SSIBs) is crucial for public safety. This study investigated the potential association between GLP-1RAs and SSIBs by exploring the FDA Adverse Event Reporting System (FAERS) database. Methods A disproportionality analysis was conducted using post-marketing data from the FAERS repository (2018 Q1 to 2022 Q4). SSIB cases associated with GLP-1RAs were identified and analyzed through disproportionality analysis using the information component. The parametric distribution with a goodness-of-fit test was employed to analyze the time-to-onset, and the Ω shrinkage was used to evaluate the potential effect of co-medication on the occurrence of SSIBs. Results In total, 204 cases of SSIBs associated with GLP-1RAs, including semaglutide, liraglutide, dulaglutide, exenatide, and albiglutide, were identified in the FAERS database. Time-of-onset analysis revealed no consistent mechanism for the latency of SSIBs in patients receiving GLP-1RAs. The disproportionality analysis did not indicate an association between GLP-1RAs and SSIBs. Co-medication analysis revealed 81 cases with antidepressants, antipsychotics, and benzodiazepines, which may be proxies of mental health comorbidities. Conclusions We found no signal of disproportionate reporting of an association between GLP-1RA use and SSIBs. Clinicians need to maintain heightened vigilance on patients premedicated with neuropsychotropic drugs. This contributes to the greater acceptance of GLP-1RAs in patients with type 2 diabetes mellitus or obesity. Graphical Abstract

Medications for Obesity

“…GI adverse effects, including oily fecal spotting (27%), fecal urgency (22%), and steatorrhea (20%), are common in the first year of orlistat use, but typically resolve within 4 weeks and can be reduced by adhering to a low-calorie diet with less than 30% of calories from fat (Table 3). Because of its mechanism of action, orlistat should be administered with meals containing some fat (10%-30% of calories) to be effective and limit adverse effects.…”

“…Clinicians should review all information available in the package insert for each medication prior to prescribing to be aware of all contraindications. In general, antiobesity medications are contraindicated among pregnant persons and individuals with known hypersensitivity to medication ingredients and are used cautiously in patients who are lactating. c Medication is approved by the US Food and Drug Administration as Schedule IV controlled substance; therefore, prescribers need to adhere to federal and state regulations for prescribing and dispensing these types of medications. d As of March 2024, package inserts for liraglutide, semaglutide, and tirzepatide include a warning about the risk of SI; however, no increased risk of suicide has been identified in monitoring studies, which was acknowledged by the US Food and Drug Administration in January 2024.…”

“… d As of March 2024, package inserts for liraglutide, semaglutide, and tirzepatide include a warning about the risk of SI; however, no increased risk of suicide has been identified in monitoring studies, which was acknowledged by the US Food and Drug Administration in January 2024.…”

Pharmacovigilance study of GLP-1 receptor agonists for metabolic and nutritional adverse events

“…Some concerns have been raised among healthcare professionals over the safety profiles of GLP-1 Ras. There have been reports of suicidal or self-injurious behaviors (SSIBs) to the European Medicines Agency (EMA), although pharmacovigilance reviews have reported no direct link between GLP-1 RAs and SSIBs ( Chen et al, 2023 ; Chen et al, 2024 ; Zhou et al, 2024 ). Increased risks of thyroid cancer and cholecystitis have been reported ( He et al, 2022 ; Bezin et al, 2023 ).…”