GLP-1 和 GIP 受体激动剂治疗帕金森病的临床和临床前研究的系统评价和荟萃分析方案。
GLP-1 and GIP receptor agonists in the treatment of Parkinson's disease: Translational systematic review and meta-analysis protocol of clinical and preclinical studies.
机构信息
Department of Pathology, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil.
Graduate Course of Pharmaceutical Sciences, University of Sorocaba (UNISO), Sorocaba, São Paulo, Brazil.
出版信息
PLoS One. 2021 Aug 12;16(8):e0255726. doi: 10.1371/journal.pone.0255726. eCollection 2021.
BACKGROUND
Parkinson's disease (PD) is a progressive multifactorial neurodegenerative condition. Epidemiological studies have shown that patients with type 2 diabetes mellitus (T2DM2) are at increased risk for developing PD, indicating a possible insulin-modulating role in this latter condition. We hypothesized that drugs similar to glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), used in the treatment of T2DM2, may play a role in PD.
OBJECTIVES
The purpose of this study is to systematically review and meta-analyze data of preclinical and clinical studies evaluating the efficacy and safety of GLP-1 and GIP drugs in the treatment of PD.
METHODS
Two reviewers will independently evaluate the studies available in the Ovid Medline, Ovid Embase, Web of Science, Cochrane Central Register of Controlled Trials, Cinahl, and Lilacs databases. Preclinical rodent or non-human primate studies and randomized controlled human clinical trials will be included, without language or publication period restrictions. Outcomes of interest in preclinical studies will be primarily locomotor improvements and adverse effects in animal models of PD. For clinical trials, we will evaluate clinical improvements rated by the Movement Disorders Society Unified Parkinson's Disease Rating Scale-parts I, II, III, and IV, and adverse effects. The risk of bias of preclinical studies will be assessed by the SYRCLE tool and CAMARADES checklist and the clinical studies by the Cochrane tool; the certainty of the evidence will be rated by GRADE.
DISCUSSION AND CONCLUSION
There is an urge for new PD treatments that may slow the progression of the disease rather than just restoring dopamine levels. This study will comprehensively review and update the state of the art of what is known about incretin hormones and PD and highlight the strengths and limitations of translating preclinical data to the clinic whenever possible.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration number CRD42020223435.
背景
帕金森病（PD）是一种进行性多因素神经退行性疾病。流行病学研究表明，2 型糖尿病（T2DM2）患者患 PD 的风险增加，表明胰岛素在后者中可能具有调节作用。我们假设，用于治疗 T2DM2 的类似胰高血糖素样肽-1（GLP-1）和胃抑制多肽（GIP）的药物可能在 PD 中发挥作用。
目的
本研究旨在系统回顾和荟萃分析评估 GLP-1 和 GIP 药物治疗 PD 的疗效和安全性的临床前和临床研究数据。
方法
两名审查员将独立评估 Ovid Medline、Ovid Embase、Web of Science、Cochrane 中央对照试验注册库、Cinahl 和 Lilacs 数据库中可用的研究。将纳入临床前啮齿动物或非人类灵长类动物研究和随机对照临床试验，无语言或出版期限限制。临床前研究的主要观察指标为运动障碍改善和 PD 动物模型中的不良反应。对于临床试验，我们将评估运动障碍学会统一帕金森病评定量表第 I、II、III 和 IV 部分的临床改善以及不良反应。临床前研究的偏倚风险将由 SYRCLE 工具和 CAMARADES 清单进行评估，临床研究将由 Cochrane 工具进行评估；证据的确定性将由 GRADE 进行评估。
讨论与结论
人们迫切需要新的 PD 治疗方法，这些方法可能会减缓疾病的进展，而不仅仅是恢复多巴胺水平。本研究将全面回顾和更新关于肠促胰岛素激素与 PD 的最新知识，并尽可能突出将临床前数据转化为临床的优势和局限性。
系统评价注册
PROSPERO 注册号 CRD42020223435。
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