Recent reports of individuals experiencing suicidal and/or self-injurious behaviors while using liraglutide and semaglutide have heightened the concerns regarding neuropsychiatric safety of Glucagon-like peptide-1 agonists (GLP-1RAs). As real-world evidence is very limited, we explored the association between GLP-1RA and suicide/self-injury by mining the FDA Adverse Event Reporting System (FAERS) database.

The FAERS database was queried from 2005 Q2 to 2023 Q2. The Reporting Odds Ratio (ROR) and Empirical Bayes Geometric Mean (EBGM) were used to conduct the disproportionality analysis.

A total of 534 GLP-1RA-associated suicide/self-injury cases were reported in the FAERS during the study period. GLP-1RA did not cause a disproportionate increase in overall suicidal and self-injurious cases (ROR: 0.16, 95%CI 0.15-0.18, P < 0.001; EBGM05: 0.15). Stratified analyses found no safety signal of suicide/injury for GLP-1RA in both females and males. The ROR for suicide/self-injury with GLP-1RA was slightly elevated (ROR: 2.50, 95%CI 1.02-6.13, P = 0.05) in children, while the EBGM05 was < 2 in this population. No significant signal value was observed in other age groups. No over-reporting of suicide/self-injury was identified for GLP-1RA before or after the COVID-19 pandemic outbreak.

The cases of suicide or self-injury reported to FAERS do not indicate any overall safety signal attributable to GLP-1RA at this time. Subgroup analysis revealed a marginal elevation of ROR for suicide and self-injury with GLP-1RA in children, but no safety signal was detected by EBGM05 in this population. Further large-scale prospective investigations are still warranted to further confirm this finding.

Glucagon-like peptide-1 (GLP-1) is an endogenous peptide that stimulates insulin secretion and decreases glucagon secretion. The use of GLP-1 receptor agonists (GLP-1RA) showed efficacy reducing the weight and glucose levels in patients with and without type 2 diabetes. This effect was also associated with a decreased risk of major cardiovascular events.

Our aim is to review the role of GLP-1RA in psychiatric patients at cardio-metabolic risk due to antipsychotics treatment.

We reviewed articles published in PubMed using the keywords: “GLP-1” “glucagon like peptide” “antipsychotics” and “psychiatry”.

The number need to treat (NNT) to achieve clinical meaningful weight loss was 3.8. GLP-1RA treatment was also associated with greater reductions in body mass index, fasting glucose, HbA1c and visceral fat. This effect is true for antipsychotic treatment in general and for those on clozapine and olanzapine in particular. Overall, the GLP-1RA are well tolerated with nausea being the most common related adverse effect. Other variables such as age, sex, psychosis severity, nausea or any adverse drug reaction did not affect the weight loss.

Studies showed a promising role in the management of antipsychotics induced weight gain, particularly in clozapine and olanzapine treated patients. Although these promising results, the route of administration, with a daily or weekly subcutaneous injection, and the GLP-1RA associated financial costs, can be viewed as important factors which can limit the wide use of this type of treatment in psychiatric patients.

No significant relationships.