{
  "abstract": "Glucagon-like peptide-1 receptor agonism has attracted interest in neurodegeneration because of its effects on metabolic and inflammatory pathways implicated in neuronal dysfunction. This narrative review examines the molecular rationale and neurological evidence for selective glucagon-like peptide-1 receptor agonists, dual agonists additionally targeting the glucose-dependent insulinotropic polypeptide receptor, and triple agonists also engaging the glucagon receptor. English-language literature retrieved from PubMed, Scopus, and Web of Science was synthesized according to study design and neurological relevance. Preclinical findings indicate modulation of insulin signaling, synaptic function, mitochondrial homeostasis, and neuroinflammation, but responses vary across compounds and experimental models. In Alzheimer’s disease, liraglutide did not meet its primary trial endpoint, and semaglutide did not slow clinical progression. Parkinson’s disease trials have yielded mixed results without establishing disease modification. Observational associations with reduced dementia risk remain susceptible to confounding. Neurological evidence for tirzepatide and retatrutide remains predominantly observational or preclinical. Greater metabolic efficacy does not establish neuroprotection, while nutritional vulnerability may constrain therapeutic applicability. Dedicated randomized trials integrating clinical outcomes with pharmacological exposure, target engagement, and metabolic mediation are required to distinguish systemic effects from direct neural actions and determine whether these therapies can prevent cognitive decline or modify established neurodegenerative disease.",
  "abstract_shown": true,
  "affiliations": [
    "Faculty of Medicine, \"Grigore T. Popa\" University of Medicine and Pharmacy, 16 Universitatii Str., 700115 Iasi, Romania.",
    "Department of Preventive Medicine and Interdisciplinarity, \"Grigore T. Popa\" University of Medicine and Pharmacy, Universitatii Str. 16, 700115 Iasi, Romania.",
    "\"Prof. Dr. Nicolae Oblu\" Emergency Clinic Hospital, 700309 Iasi, Romania.",
    "2nd Internal Medicine Department, \"Grigore T. Popa\" University of Medicine and Pharmacy, 700115 Iasi, Romania."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Elena Popa",
      "orcid": "0000-0003-2207-5129"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Andrei Emilian Popa",
      "orcid": "0000-0002-1622-2543"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Vladimir Poroch",
      "orcid": "0000-0002-2503-5395"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Thomas Gabriel Schreiner",
      "orcid": "0000-0002-4495-4004"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Ana Maria Slanina"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mihaela Poroch"
    },
    {
      "affs": [
        0
      ],
      "name": "Alexandru Matei Hatneanu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Monica Iuliana Ungureanu"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Antoneta Dacia Petroaie",
      "orcid": "0000-0002-1239-8058"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Agnes Iacinta Bacusca"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Elena Adorata Coman"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/99nwejsht7n5c.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27198738",
  "fulltext_url": "https://europepmc.org/articles/PMC13664769",
  "id": "99nwejsht7n5c",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/19/8738",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7214907674",
  "pdf_url": "https://europepmc.org/articles/PMC13664769?pdf=render",
  "pmcid": "PMC13664769",
  "pmid": "42883986",
  "published": "2026-09-30",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/99nwejsht7n5c.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:55Z",
      "native_id": "10.3390/ijms27198738",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/19/8738"
    },
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42883986",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42883986"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Alzheimer's disease research and treatments",
      "subfield": "physiology"
    }
  ],
  "title": "GLP-1, GIP, and Glucagon Receptor Agonism at the Obesity–Neurodegeneration Interface: A Narrative Review",
  "title_text": "GLP-1, GIP, and Glucagon Receptor Agonism at the Obesity–Neurodegeneration Interface: A Narrative Review",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/99nwejsht7n5c",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}