Psychiatric and psychological adverse effects associated with dulaglutide, semaglutide, and liraglutide: A vigibase study
Abstract
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are crucial in managing type 2 diabetes mellitus (T2DM) and obesity. Agents like dulaglutide, semaglutide, and liraglutide mimic endogenous GLP-1, enhancing insulin secretion and promoting satiety. Beyond glycemic control, they offer cardioprotective and neuroprotective benefits. However, concerns about psychiatric adverse effects have emerged, necessitating a systematic assessment of their safety profile. MATERIAL & METHODS: This multinational pharmacovigilance study utilized VigiBase® data up to December 1, 2024, focusing on adverse drug reaction (ADR) reports for GLP-1 RAs. Psychiatric ADRs were classified using MedDRA terminology. Disproportionality analyses were conducted via logistic regression to calculate reporting adjusted Reporting Odds Ratios (aRORs) within reports involving antidiabetic or anti-obesity medications. A causal forest model assessed the individual treatment effect (ITE) of semaglutide on depression and suicidality reporting. RESULTS: Among 2,061,901 reports, 21,414 involved psychiatric ADRs for GLP-1 RAs. Significant signals were observed for anxiety (aROR: 1.26, 95%CI: 1.18-1.35), depressed mood disorders (aROR: 1.70, 95%CI: 1.57-1.84) and suicidality (aROR 1.45, 95%CI: 1.29-1.63) with semaglutide, and eating disorders with all three GLP-1 RAs (aRORs between 4.17 and 6.80). The causal forest model estimated an average treatment effect of 0.0046 for semaglutide on depression and suicidality reporting, with significant heterogeneity across regions and demographic groups. DISCUSSION: The study found no significant increase in overall psychiatric ADR reporting for GLP-1 RAs, except for eating disorders and depression/suicidality in semaglutide-treated patients. Sensitivity analyses before June 4, 2021, found no signals, aligning with RCT data. Post-marketing reports linked semaglutide to depression and suicidal ideation, prompting regulatory investigations. The causal forest model revealed significant heterogeneity in the psychiatric safety profile of semaglutide, with regional factors influencing ADR reporting. CONCLUSION: While GLP-1 RAs do not show a significant increase in overall psychiatric ADR reporting, findings suggest that clinicians should remain vigilant for potential depressive symptoms and suicidality, particularly in individuals with obesity treated with semaglutide since its approval for weight management.
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BibTeX
@article{nishida2026psychiatric,
title = {{Psychiatric and psychological adverse effects associated with dulaglutide, semaglutide, and liraglutide: A vigibase study}},
author = {Kazuki Nishida and Basile Chrétien and Charles Dolladille and Takumi Ebina and Branko Aleksic and Nicolas Cabé and Véronique Savey and Takeshi Onoue and Hiroshi Yatsuya},
journal = {Clinical Nutrition},
year = {2026},
month = sep,
doi = {10.1016/j.clnu.2025.06.011},
url = {https://hal.science/hal-05746270v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Psychiatric and psychological adverse effects associated with dulaglutide, semaglutide, and liraglutide: A vigibase study
AU - Kazuki Nishida
AU - Basile Chrétien
AU - Charles Dolladille
AU - Takumi Ebina
AU - Branko Aleksic
AU - Nicolas Cabé
AU - Véronique Savey
AU - Takeshi Onoue
AU - Hiroshi Yatsuya
PY - 2026
DA - 2026/09/11
JO - Clinical Nutrition
DO - 10.1016/j.clnu.2025.06.011
UR - https://hal.science/hal-05746270v1
AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are crucial in managing type 2 diabetes mellitus (T2DM) and obesity. Agents like dulaglutide, semaglutide, and liraglutide mimic endogenous GLP-1, enhancing insulin secretion and promoting satiety. Beyond glycemic control, they offer cardioprotective and neuroprotective benefits. However, concerns about psychiatric adverse effects have emerged, necessitating a systematic assessment of their safety profile. MATERIAL & METHODS: This multinational pharmacovigilance study utilized VigiBase® data up to December 1, 2024, focusing on adverse drug reaction (ADR) reports for GLP-1 RAs. Psychiatric ADRs were classified using MedDRA terminology. Disproportionality analyses were conducted via logistic regression to calculate reporting adjusted Reporting Odds Ratios (aRORs) within reports involving antidiabetic or anti-obesity medications. A causal forest model assessed the individual treatment effect (ITE) of semaglutide on depression and suicidality reporting. RESULTS: Among 2,061,901 reports, 21,414 involved psychiatric ADRs for GLP-1 RAs. Significant signals were observed for anxiety (aROR: 1.26, 95%CI: 1.18-1.35), depressed mood disorders (aROR: 1.70, 95%CI: 1.57-1.84) and suicidality (aROR 1.45, 95%CI: 1.29-1.63) with semaglutide, and eating disorders with all three GLP-1 RAs (aRORs between 4.17 and 6.80). The causal forest model estimated an average treatment effect of 0.0046 for semaglutide on depression and suicidality reporting, with significant heterogeneity across regions and demographic groups. DISCUSSION: The study found no significant increase in overall psychiatric ADR reporting for GLP-1 RAs, except for eating disorders and depression/suicidality in semaglutide-treated patients. Sensitivity analyses before June 4, 2021, found no signals, aligning with RCT data. Post-marketing reports linked semaglutide to depression and suicidal ideation, prompting regulatory investigations. The causal forest model revealed significant heterogeneity in the psychiatric safety profile of semaglutide, with regional factors influencing ADR reporting. CONCLUSION: While GLP-1 RAs do not show a significant increase in overall psychiatric ADR reporting, findings suggest that clinicians should remain vigilant for potential depressive symptoms and suicidality, particularly in individuals with obesity treated with semaglutide since its approval for weight management.
SN - 0261-5614
SN - 1532-1983
ER -