{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:28:29Z","timestamp":1792164509560,"version":"4.4.0"},"reference-count":28,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objective: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) exhibit neuroprotective properties in preclinical models of Alzheimer\u2019s disease (AD), reducing amyloid accumulation, neuroinflammation, and insulin resistance within the brain. However, clinical evidence regarding their cognitive effects in AD and mild cognitive impairment (MCI) remains inconclusive. To evaluate the effects of GLP-1 RAs on cognitive outcomes in patients with AD or MCI due to AD. Methods: A systematic review was conducted according to PRISMA 2020 and registered in PROSPERO (CRD420251143171). Although the original registry was broad, the identification of a small set of homogeneous randomized controlled trials (RCTs) during screening, prior to data extraction, allowed for a random-effects meta-analysis of cognitive outcomes. RCTs enrolling adults with clinically or biomarker-confirmed AD or MCI were included. Interventions comprised liraglutide or exenatide compared with placebo. Standardized mean differences (SMD) in global cognitive scores were pooled using a random-effects model (restricted maximum likelihood [REML] estimator with Hartung\u2013Knapp adjustment). Results: Three randomized trials (n = 278 participants; 51% women; mean age 68 \u00b1 7 years) met inclusion criteria. Treatment duration ranged from 26 weeks to 18 months. Pooled analysis revealed no significant effect of GLP-1 RAs on global cognition compared with placebo \u22120.21 (95% CI \u22120.81 to 0.38; I2 = 47%; \u03c42 = 3.77). Sensitivity analyses restricted to liraglutide or studies \u2265 12 months yielded similar results. Conclusions: Current randomized evidence does not support cognitive improvement with GLP-1 RAs in AD or MCI.<\/jats:p>","DOI":"10.3390\/pharmaceutics18010069","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:28:57Z","timestamp":1767626937000},"page":"69","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Liraglutide and Exenatide in Alzheimer\u2019s Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Cognitive Outcomes"],"prefix":"10.3390","volume":"18","author":[{"given":"Paula","family":"Santos","sequence":"first","affiliation":[{"name":"Graduate Program in Human Movement and Rehabilitation, Evangelical University of Goi\u00e1s (UniEVANG\u00c9LICA), An\u00e1polis 75083-515, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9434-4231","authenticated-orcid":false,"given":"Alberto Souza","family":"S\u00e1 Filho","sequence":"additional","affiliation":[{"name":"Graduate Program in Human Movement and Rehabilitation, Evangelical University of Goi\u00e1s (UniEVANG\u00c9LICA), An\u00e1polis 75083-515, GO, Brazil"},{"name":"Graduate Program in Pharmaceutical Sciences, Pharmacology and Therapeutics, Evangelical University of Goi\u00e1s (UniEVANG\u00c9LICA), An\u00e1polis 75083-515, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7285-2742","authenticated-orcid":false,"given":"Vicente","family":"Aprigliano","sequence":"additional","affiliation":[{"name":"Escuela de Ingenier\u00eda de Construcci\u00f3n y Transporte, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Avda Brasil 2147, Valpara\u00edso 2362804, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda G.","family":"Duarte","sequence":"additional","affiliation":[{"name":"Department of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7585-0930","authenticated-orcid":false,"given":"Nat\u00e3 Alegransi","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Departament of Medicine, Universidade de Passo Fundo, Passo Fundo 99052-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia Marques","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Biomechanics Laboratory, University of the State of Santa Catarina, UDESC Cefid, Florian\u00f3polis 88040-900, SC, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7440-7581","authenticated-orcid":false,"given":"James Oluwagbamigbe","family":"Fajemiroye","sequence":"additional","affiliation":[{"name":"Graduate Program in Pharmaceutical Sciences, Pharmacology and Therapeutics, Evangelical University of Goi\u00e1s (UniEVANG\u00c9LICA), An\u00e1polis 75083-515, GO, Brazil"},{"name":"Institute of Biological Sciences (ICB), Universidade Federal de Goi\u00e1s (UFG), Goi\u00e2nia 74690-900, GO, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur Prediger","family":"Buchholz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-903, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Renault","family":"Vaz","sequence":"additional","affiliation":[{"name":"Mount Auburn Hospital, Harvard Medical School, Cambridge, MA 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0440-8404","authenticated-orcid":false,"given":"Gaspar R.","family":"Chiappa","sequence":"additional","affiliation":[{"name":"Graduate Program in Human Movement and Rehabilitation, Evangelical University of Goi\u00e1s (UniEVANG\u00c9LICA), An\u00e1polis 75083-515, GO, Brazil"},{"name":"Faculty of Health Sciences, Universidad Aut\u00f3noma de Chile, Providencia 7500912, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2023). 2023 Alzheimer\u2019s disease facts and figures. 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