{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:03:29Z","timestamp":1787162609970,"version":"build-2736575974"},"reference-count":38,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Neurol Disord"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as potential neuroprotective agents for Parkinson\u2019s disease (PD). However, evidence regarding their efficacy remains inconclusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources:<\/jats:title>\n                    <jats:p>PubMed, Embase, and the Cochrane Library were searched through April 14, 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>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\u2019s Disease Rating Scale (MDS-UPDRS) scores.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      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 \u22122.06 (95% confidence interval (CI): \u22124.09; \u22120.03;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200956%), 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\u2019s Disease Questionnaire-39, Non-Motor Symptoms Scale for Parkinson\u2019s Disease, UDysRS). A nonsignificant trend toward increased serious adverse events or treatment discontinuation was observed (odds ratio\u2009=\u20091.52; 95% CI: 0.66; 3.50), with low heterogeneity. TSA for secondary outcomes indicated that additional trials are required.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:<\/jats:title>\n                    <jats:p>INPLASY2024110119.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17562864251372747","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T10:04:09Z","timestamp":1757585049000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["GLP-1 receptor agonists in Parkinson\u2019s disease progression: a meta-analysis with trial sequential analysis of randomized controlled trials"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1484-8016","authenticated-orcid":false,"given":"Wen-Wen","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Neurology, Chi-Mei Medical Center, Tainan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan-Hsien","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Chi-Mei Medical Center, Tainan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jheng-Yan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Chi Mei Medical Center, Tainan, Taiwan"},{"name":"Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Hsiang","family":"Chuang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jui-Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan"},{"name":"Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Cheng","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo Chuan","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan"},{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Tsang","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Chi Mei Medical Center, No. 901, Zhonghua Road, Yongkang District, Tainan City 710, Taiwan"},{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2401857"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033447"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70218-0"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15030770"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2020.101102"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-024-01025-6"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113222"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom14070872"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2016.01.013"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2021.114578"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68295"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31585-4"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00378-2"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2312323"},{"key":"e_1_3_4_16_2","unstructured":"jRCT J. 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