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Introduction <p>Regulatory reviews in 2023–2024 reignited concern about possible suicidality with Glucagon-like peptide-1 (GLP-1) receptor agonists used for weight management. While clinical trials and real-world studies have not confirmed an increased risk, comparative post-marketing analyses across all anti-obesity agents are scarce.</p> Aim <p>To compare disproportional reporting of suicidality-related adverse events among GLP-1/dual incretin versus non-GLP-1 anti-obesity drugs in the FDA Adverse Event Reporting System (FAERS).</p> Method <p>We conducted a retrospective disproportionality study using FAERS (January 2012–February 2025). Reports submitted from the United States with the study drug listed as primary suspect were retrieved via openFDA. Suicidality terms were predefined (MedDRA Preferred Terms: suicidal ideation, suicide attempt, completed suicide). Reporting Odds Ratios (RORs) with 95% confidence intervals (CIs) were calculated for each drug and at class level (GLP-1/dual incretin vs non-GLP-1). Haldane–Anscombe corrections were applied where needed.</p> Results <p>Among approximately 78,000 anti-obesity reports, 207 (approximately 0.3%) involved suicidality-related events. For semaglutide, RORs were 1.39 (95% CI 0.99–1.94) for suicidal ideation, 1.38 (0.46–4.15) for suicide attempt, and 1.72 (0.62–4.74) for completed suicide, none statistically significant. Liraglutide showed ROR 1.01 (0.66–1.55) for suicidal ideation and 18.11 (6.96–47.15) for completed suicide based on 14 cases. Tirzepatide yielded RORs below unity for all outcomes. Naltrexone/bupropion showed elevated disproportional reporting for suicidal ideation (ROR 3.84; 95% CI 2.89–5.12) and suicide attempt (ROR 4.11; 95% CI 1.62–10.45.</p> Conclusion <p>GLP-1 and dual-incretin agents did not show disproportionality signals for suicidal ideation or suicide attempt. A statistically significant disproportionality signal for completed suicide was observed for liraglutide; however, this estimate was based on few cases and displayed wide confidence intervals, warranting cautious interpretation. These findings support an overall neutral psychiatric safety profile for incretin-based therapies while underscoring the need for continued monitoring of rare events such as completed suicide.</p>

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Comparative pharmacovigilance analysis of suicidality-related adverse events among GLP-1 and non-GLP-1 anti-obesity drugs in the FDA Adverse Event Reporting System

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月25日

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  • Jose Seijas-Amigo,
  • Ángel Salgado-Barreira,
  • Diego Rodriguez-Penas,
  • Begoña Cardeso-Paredes,
  • Marta Ribeiro-Ferreiro,
  • Moisés Rodriguez-Mañero,
  • Jose Ramon Gonzalez-Juanatey

摘要

Introduction

Regulatory reviews in 2023–2024 reignited concern about possible suicidality with Glucagon-like peptide-1 (GLP-1) receptor agonists used for weight management. While clinical trials and real-world studies have not confirmed an increased risk, comparative post-marketing analyses across all anti-obesity agents are scarce.

Aim

To compare disproportional reporting of suicidality-related adverse events among GLP-1/dual incretin versus non-GLP-1 anti-obesity drugs in the FDA Adverse Event Reporting System (FAERS).

Method

We conducted a retrospective disproportionality study using FAERS (January 2012–February 2025). Reports submitted from the United States with the study drug listed as primary suspect were retrieved via openFDA. Suicidality terms were predefined (MedDRA Preferred Terms: suicidal ideation, suicide attempt, completed suicide). Reporting Odds Ratios (RORs) with 95% confidence intervals (CIs) were calculated for each drug and at class level (GLP-1/dual incretin vs non-GLP-1). Haldane–Anscombe corrections were applied where needed.

Results

Among approximately 78,000 anti-obesity reports, 207 (approximately 0.3%) involved suicidality-related events. For semaglutide, RORs were 1.39 (95% CI 0.99–1.94) for suicidal ideation, 1.38 (0.46–4.15) for suicide attempt, and 1.72 (0.62–4.74) for completed suicide, none statistically significant. Liraglutide showed ROR 1.01 (0.66–1.55) for suicidal ideation and 18.11 (6.96–47.15) for completed suicide based on 14 cases. Tirzepatide yielded RORs below unity for all outcomes. Naltrexone/bupropion showed elevated disproportional reporting for suicidal ideation (ROR 3.84; 95% CI 2.89–5.12) and suicide attempt (ROR 4.11; 95% CI 1.62–10.45.

Conclusion

GLP-1 and dual-incretin agents did not show disproportionality signals for suicidal ideation or suicide attempt. A statistically significant disproportionality signal for completed suicide was observed for liraglutide; however, this estimate was based on few cases and displayed wide confidence intervals, warranting cautious interpretation. These findings support an overall neutral psychiatric safety profile for incretin-based therapies while underscoring the need for continued monitoring of rare events such as completed suicide.