GLP-1 receptor agonists in Parkinson's disease progression: a meta-analysis with trial sequential analysis of randomized controlled trials.

IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY
Therapeutic Advances in Neurological Disorders Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI:10.1177/17562864251372747
Wen-Wen Tsai, Kuan-Hsien Lu, Jheng-Yan Wu, Min-Hsiang Chuang, Jui-Yi Chen, Chih-Cheng Lai, Kuo Chuan Hung, Meng-Tsang Hsieh
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引用次数: 0

Abstract

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as potential neuroprotective agents for Parkinson's disease (PD). However, evidence regarding their efficacy remains inconclusive.

Objective: To assess the therapeutic effects and safety profile of GLP-1 RAs in patients with mild-to-moderate PD. We aim to conduct an updated systematic review to evaluate the effects of GLP-1 RAs in patients with mild-to-moderate PD.

Design: Systematic review and meta-analysis of randomized controlled trials (RCTs) with trial sequential analysis (TSA) and Grading of Recommendations, Assessment, Development, and Evaluations certainty assessment.

Data sources: PubMed, Embase, and the Cochrane Library were searched through April 14, 2025.

Methods: We conducted a systematic review and meta-analysis of RCTs with TSA comparing GLP-1 RAs to placebo in patients with mild-to-moderate PD. The primary outcome was change in the Movement Disorder Society-unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores.

Results: Five RCTs involving a total of 708 nondiabetic patients with mild-to-moderate PD were included. GLP-1 RAs significantly attenuated motor symptom progression, as evidenced by a mean difference in MDS-UPDRS Part III (off medication) of -2.06 (95% confidence interval (CI): -4.09; -0.03; I 2 = 56%), with conclusive evidence supported by TSA. No statistically significant improvements were observed in other MDS-UPDRS domains, levodopa equivalent daily dose reduction, or functional scales (Parkinson's Disease Questionnaire-39, Non-Motor Symptoms Scale for Parkinson's Disease, UDysRS). A nonsignificant trend toward increased serious adverse events or treatment discontinuation was observed (odds ratio = 1.52; 95% CI: 0.66; 3.50), with low heterogeneity. TSA for secondary outcomes indicated that additional trials are required.

Conclusion: GLP-1 RAs may provide a modest benefit in slowing motor progression in PD. However, their effects on nonmotor symptoms, medication use, and long-term safety remain uncertain due to the limited number of available trials. Further large-scale, long-duration trials are warranted.

Trial registration: INPLASY2024110119.

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GLP-1受体激动剂在帕金森病进展中的作用:随机对照试验的荟萃分析
背景:胰高血糖素样肽-1受体激动剂(GLP-1 RAs)已成为帕金森病(PD)的潜在神经保护剂。然而,关于其功效的证据仍然不确定。目的:评价GLP-1 RAs治疗轻中度帕金森病的疗效和安全性。我们的目标是进行一项更新的系统综述,以评估GLP-1 RAs在轻度至中度PD患者中的作用。设计:随机对照试验(rct)的系统回顾和荟萃分析,采用试验序列分析(TSA)和推荐评分、评估、发展和评估确定性评估。数据来源:PubMed, Embase和Cochrane图书馆被检索到2025年4月14日。方法:我们对使用TSA比较GLP-1 RAs与安慰剂治疗轻至中度PD患者的随机对照试验进行了系统回顾和荟萃分析。主要结果是运动障碍学会统一帕金森病评定量表(MDS-UPDRS)评分的变化。结果:纳入5项随机对照试验,共708例轻度至中度PD的非糖尿病患者。GLP-1 RAs显著减轻运动症状进展,MDS-UPDRS第三部分(停药)的平均差异为-2.06(95%置信区间(CI): -4.09;-0.03;i2 = 56%), TSA提供了确凿的证据。在MDS-UPDRS的其他领域、左旋多巴当量日剂量减少或功能量表(帕金森病问卷-39,帕金森病非运动症状量表,UDysRS)中没有观察到统计学上显著的改善。观察到严重不良事件或停药增加的趋势不显著(优势比= 1.52;95% CI: 0.66; 3.50),异质性低。次要结果的TSA显示需要额外的试验。结论:GLP-1 RAs可能在减缓PD的运动进展中提供适度的益处。然而,由于可用的试验数量有限,它们对非运动症状、药物使用和长期安全性的影响仍不确定。进一步大规模、长时间的试验是必要的。试验注册:INPLASY2024110119。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.30
自引率
1.70%
发文量
62
审稿时长
15 weeks
期刊介绍: Therapeutic Advances in Neurological Disorders is a peer-reviewed, open access journal delivering the highest quality articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of neurology. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in neurology, providing a forum in print and online for publishing the highest quality articles in this area.
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