杜拉鲁肽、西马鲁肽和利拉鲁肽相关的精神和心理不良反应：一项基础研究

IF 7.4 2区医学 Q1 NUTRITION & DIETETICS

Clinical nutrition Pub Date : 2025-06-23 DOI:10.1016/j.clnu.2025.06.011

Kazuki Nishida , Basile Chrétien , Charles Dolladille , Takumi Ebina , Branko Aleksic , Nicolas Cabé , Véronique Savey , Takeshi Onoue , Hiroshi Yatsuya

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引用次数: 0

摘要

胰高血糖素样肽-1受体激动剂（GLP-1 RAs）在治疗2型糖尿病（T2DM）和肥胖中至关重要。杜拉鲁肽、西马鲁肽和利拉鲁肽等药物模拟内源性GLP-1，增强胰岛素分泌，促进饱腹感。除了控制血糖，它们还能保护心脏和神经。然而，对精神病学不良反应的担忧已经出现，有必要对其安全性进行系统评估。材料,方法：这项跨国药物警戒研究利用截至2024年12月1日的VigiBase®数据，重点关注GLP-1 RAs的药物不良反应（ADR）报告。使用MedDRA术语对精神病学不良反应进行分类。通过逻辑回归进行歧化分析，以计算涉及抗糖尿病或抗肥胖药物的报告中调整后的报告优势比（aRORs）。因果森林模型评估了西马鲁肽对抑郁症和自杀报告的个体治疗效果（ITE）。结果在2,061,901份报告中，21,414份涉及GLP-1 RAs的精神病学不良反应。在使用西马鲁肽治疗焦虑症（aROR: 1.26, 95%CI: 1.18-1.35）、抑郁情绪障碍（aROR: 1.70, 95%CI: 1.57-1.84）、自杀倾向（aROR 1.45, 95%CI: 1.29-1.63）和三种GLP-1 RAs治疗饮食失调（aROR在4.17 - 6.80之间）方面观察到显著信号。因果森林模型估计，西马鲁肽对抑郁症和自杀报告的平均治疗效果为0.0046，在不同地区和人口群体中存在显著的异质性。研究发现，除了西马鲁肽治疗患者的饮食失调和抑郁/自杀外，GLP-1 RAs的总体精神不良反应报告没有显著增加。在2021年6月4日之前的敏感性分析中，未发现任何信号，与RCT数据一致。上市后报告将西马鲁肽与抑郁症和自杀意念联系起来，促使监管机构进行调查。因果森林模型显示，西马鲁肽在精神病学安全性方面存在显著异质性，区域因素影响不良反应报告。结论：虽然GLP-1 RAs在总体精神不良反应报告中没有显著增加，但研究结果表明，临床医生应该对潜在的抑郁症状和自杀行为保持警惕，特别是在西马鲁肽被批准用于体重管理后接受治疗的肥胖患者。

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Psychiatric and psychological adverse effects associated with dulaglutide, semaglutide, and liraglutide: A vigibase study

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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来源期刊

Clinical nutrition 医学-营养学

CiteScore

14.10

自引率

6.30%

发文量

356

审稿时长

28 days

期刊介绍： Clinical Nutrition, the official journal of ESPEN, The European Society for Clinical Nutrition and Metabolism, is an international journal providing essential scientific information on nutritional and metabolic care and the relationship between nutrition and disease both in the setting of basic science and clinical practice. Published bi-monthly, each issue combines original articles and reviews providing an invaluable reference for any specialist concerned with these fields.