{"title":"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","authors":"Wen-Wen Tsai, Kuan-Hsien Lu, Jheng-Yan Wu, Min-Hsiang Chuang, Jui-Yi Chen, Chih-Cheng Lai, Kuo Chuan Hung, Meng-Tsang Hsieh","doi":"10.1177/17562864251372747","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Design: </strong>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.</p><p><strong>Data sources: </strong>PubMed, Embase, and the Cochrane Library were searched through April 14, 2025.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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>I</i> <sup>2</sup> = 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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>INPLASY2024110119.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251372747"},"PeriodicalIF":4.1000,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12426393/pdf/","citationCount":"0","resultStr":"{\"title\":\"GLP-1 receptor agonists in Parkinson's disease progression: a meta-analysis with trial sequential analysis of randomized controlled trials.\",\"authors\":\"Wen-Wen Tsai, Kuan-Hsien Lu, Jheng-Yan Wu, Min-Hsiang Chuang, Jui-Yi Chen, Chih-Cheng Lai, Kuo Chuan Hung, Meng-Tsang Hsieh\",\"doi\":\"10.1177/17562864251372747\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Design: </strong>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.</p><p><strong>Data sources: </strong>PubMed, Embase, and the Cochrane Library were searched through April 14, 2025.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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>I</i> <sup>2</sup> = 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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Trial registration: </strong>INPLASY2024110119.</p>\",\"PeriodicalId\":22980,\"journal\":{\"name\":\"Therapeutic Advances in Neurological Disorders\",\"volume\":\"18 \",\"pages\":\"17562864251372747\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-09-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12426393/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Neurological Disorders\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17562864251372747\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Neurological Disorders","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17562864251372747","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
GLP-1 receptor agonists in Parkinson's disease progression: a meta-analysis with trial sequential analysis of randomized controlled trials.
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; I2 = 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.
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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