Psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide: a pharmacovigilance analysis of individual case safety reports submitted to the EudraVigilance database

Int J Clin Pharm. 2024 Apr;46(2):488-495. doi: 10.1007/s11096-023-01694-7. Epub 2024 Jan 24.

Abstract

Background: Semaglutide, liraglutide and tirzepatide are glucagon-like peptide-1 (GLP-1) receptor agonists that are effective for weight reduction. Recent reports of patients experiencing suicidal thoughts and other psychiatric adverse events while using GLP-1 agonists have raised concerns about the potential risk of self-harm and led the European Medicines Agency to investigate these medications.

Aim: To identify and analyse the psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide.

Method: All individual case safety reports for semaglutide, liraglutide, and tirzepatide reported to the EudraVigilance database from 01/01/2021 to 30/05/2023 were analysed. Descriptive statistics were used to explore study population characteristics.

Results: During the study period, 31,444 adverse event reports were identified: semaglutide (n = 13,956; 44.4%), liraglutide (n = 16,748; 53.2%), and tirzepatide (n = 740; 2.3%). There were 372 reports with psychiatric adverse event reports (n = 372; 1.18%) with a total of 481 adverse events. Women accounted for 65% (n = 242) of these reports. Depression was the most commonly reported adverse event (n = 187; 50.3%), followed by anxiety (n = 144; 38.7%) and suicidal ideation (n = 73; 19.6%). Nine deaths (8 with liraglutide and 1 with semaglutide) and 11 life-threatening outcomes (4 associated with liraglutide and 7 with semaglutide) were reported. The fatal outcomes occurred primarily among men (8 out of 9) resulting from completed suicidal attempts and depression.

Conclusion: Psychiatric adverse events comprised only 1.2% of the total reports for semaglutide, liraglutide, and tirzepatide. However, the severity and fatal outcomes of some of these reports warrant further investigation.

Keywords: Liraglutide; Obesity; Psychiatric adverse events; Semaglutide; Suicide; Tirzepatide.

MeSH terms

  • Diabetes Mellitus, Type 2* / drug therapy
  • Female
  • Gastric Inhibitory Polypeptide*
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glucagon-Like Peptide-1 Receptor / therapeutic use
  • Glucagon-Like Peptide-2 Receptor*
  • Glucagon-Like Peptides*
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Liraglutide* / adverse effects
  • Male
  • Pharmacovigilance

Substances

  • Liraglutide
  • Hypoglycemic Agents
  • semaglutide
  • tirzepatide
  • Glucagon-Like Peptide-1 Receptor
  • Glucagon-Like Peptide-2 Receptor
  • Glucagon-Like Peptides
  • Gastric Inhibitory Polypeptide