{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T23:14:57Z","timestamp":1789082097357,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Parkinson's disease (PD) is a progressive neurodegenerative disorder with no currently approved disease\u2010modifying treatments. Glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs), originally used in type 2 diabetes, have demonstrated neuroprotective and anti\u2010inflammatory effects in preclinical PD models. This systematic review and meta\u2010analysis evaluated the efficacy and safety of GLP\u20101RAs in patients with PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic search of MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov was conducted through July 2025 for randomized controlled trials (RCTs) comparing GLP\u20101RAs to placebo in PD. Primary outcomes included MDS\u2010UPDRS Part III (motor examination) both on and off medication. Secondary outcomes included MDS\u2010UPDRS Parts I, II, IV, PDQ\u201039, NMSS, and adverse effects. Data were pooled using a random\u2010effects model with results reported as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Five RCTs involving 708 participants were included. No statistically significant differences were found in MDS\u2010UPDRS Part III scores off medication (MD: \u20132.00, 95% CI: \u20134.12 to 0.11, p = 0.06) or on medication (MD: \u20131.40, 95% CI: \u20133.42 to 0.62, p = 0.17). Secondary outcomes also showed no significant benefits with GLP\u20101RA use. However, GLP\u20101RAs were associated with increased gastrointestinal side effects, including nausea (RR: 2.09), vomiting (RR: 4.53), constipation (RR: 1.60), and weight loss (RR: 1.83).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Current evidence does not demonstrate a statistically significant overall benefit of GLP\u20101RAs on efficacy outcomes in PD, while gastrointestinal adverse events are increased. More trials are needed to clarify their disease\u2010modifying potential.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71344","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T16:39:00Z","timestamp":1774456740000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy and Safety of Glucagon\u2010Like Peptide 1 Receptor Agonists in Parkinson Disease: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"16","author":[{"given":"Hassan","family":"Raza","sequence":"first","affiliation":[{"name":"Department of Medicine Lahore Medical and Dental College  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bakhtmeena","family":"Nizam","sequence":"additional","affiliation":[{"name":"Department of Medicine Women Medical College  Abbotabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arif","family":"Padaniya","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Aqib","family":"Farid","sequence":"additional","affiliation":[{"name":"Department of Geriatrics Oxleas NHS Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Nabi","sequence":"additional","affiliation":[{"name":"Department of Medicine Ziauddin University  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Qasim","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Medicine Allama Iqbal Medical College  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Salih","sequence":"additional","affiliation":[{"name":"Department of Medicine Dow University Hospital  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apurva Hiteshkumar","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noora","family":"Inam","sequence":"additional","affiliation":[{"name":"Department of Medicine Gajju Khan Medical College  Swabi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Ebad Ur","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Medicine Rawalpindi Medical University  Rawalpindi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usman","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Neurology Geisinger Hospital  Scranton Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma'a Munasar Ali","family":"Alsubari","sequence":"additional","affiliation":[{"name":"Department of Medicine Sana'a University  Sana'a Yemen"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140\u20106736(91)92989\u2010f"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2024.107220"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.22360"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(17)31585\u20104"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68295"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(21)00218\u2010X"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13041158"},{"key":"e_1_2_10_9_1","unstructured":"Cochrane. \u201cCochrane Handbook for Systematic Reviews of Interventions.\u201d Accessed July 5 2024.https:\/\/training.cochrane.org\/handbook."},{"key":"e_1_2_10_10_1","volume-title":"StatPearls","author":"Collins L.","year":"2025"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prdoa.2022.100133"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD\u2010181474"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2019.104583"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm12020144"},{"key":"e_1_2_10_15_1","doi-asserted-by":"crossref","unstructured":"Hogg E. 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