Bushi Ganesh, Khatib Mahalaqua Nazli, Rohilla Shivam, Singh Mahendra Pratap, Uniyal Nidhi, Ballal Suhas, Bansal Pooja, Bhopte Kiran, Gupta Manika, Gaidhane Abhay M, Tomar Balvir S, Ashraf Ayash, Ravi Kumar M, Chauhan Ashish Singh, Sah Sanjit, Serhan Hashem Abu, Shabil Muhammed
School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India.
Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India.
Diabetes Metab Res Rev. 2025 Feb;41(2):e70037. doi: 10.1002/dmrr.70037.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used to treat type 2 diabetes and obesity, providing metabolic and cardiovascular benefits. However, concerns have emerged about potential neuropsychiatric side effects, including suicidal ideation and behaviour, prompting investigations by regulatory bodies such as the FDA and EMA. This systematic review and meta-analysis aimed to assess the association between GLP-1RA use and the risk of suicidal ideation or behaviour.
A systematic literature search was conducted in PubMed, Embase, and Web of Science through September 2024, adhering to PRISMA guidelines. Observational cohort and case-control studies reporting suicidal ideation or behaviour in adults using GLP-1RAs were included. The Modified Newcastle-Ottawa Scale assessed risk of bias, and random-effect models calculated risk ratios (RR) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I statistic.
Of 126 studies, 11 were included from multiple countries with diverse designs. The meta-analysis of four studies showed no statistically significant difference in suicidal outcomes between GLP-1RA users and users of other anti-hyperglycaemic drugs (RR: 0.568, 95% CI: 0.077-4.205). Substantial heterogeneity was observed (I = 98%). Pharmacovigilance studies indicated no disproportionate increase in suicidality, while some observational studies suggested a lower risk.
This review found no significant link between GLP-1RA use and increased suicidal ideation or behaviour. However, the high heterogeneity and reliance on pharmacovigilance data suggest caution. Clinicians should monitor patients, particularly those with psychiatric conditions, and further research is needed to assess long-term neuropsychiatric safety.
胰高血糖素样肽-1受体激动剂（GLP-1RAs）被广泛用于治疗2型糖尿病和肥胖症，具有代谢和心血管方面的益处。然而，人们对其潜在的神经精神副作用，包括自杀意念和行为，产生了担忧，促使美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）等监管机构进行调查。本系统评价和荟萃分析旨在评估使用GLP-1RAs与自杀意念或行为风险之间的关联。
按照PRISMA指南，于2024年9月前在PubMed、Embase和Web of Science中进行了系统的文献检索。纳入了报告使用GLP-1RAs的成年人自杀意念或行为的观察性队列研究和病例对照研究。采用改良的纽卡斯尔-渥太华量表评估偏倚风险，随机效应模型计算风险比（RR）及95%置信区间（CI）。使用I²统计量评估异质性。
在126项研究中，有11项来自多个国家，设计多样。对4项研究的荟萃分析显示，GLP-1RA使用者与其他降糖药物使用者在自杀结局方面无统计学显著差异（RR：0.568，95%CI：0.077 - 4.205）。观察到存在显著异质性（I² = 98%）。药物警戒研究表明自杀倾向没有不成比例的增加，而一些观察性研究则提示风险较低。
本综述发现使用GLP-1RAs与自杀意念或行为增加之间无显著关联。然而，高度的异质性以及对药物警戒数据的依赖表明需谨慎。临床医生应监测患者，尤其是有精神疾病的患者，还需要进一步研究来评估长期的神经精神安全性。
