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Study · Systematic review · 2026

7 results

The effects of GLP-1 receptor agonists on Alzheimer's pathophysiology: A systematic review.

Corcoran E, Kettlety M, Mogul U, Azah JN, Cork SC

Molecular and cellular neurosciences20 Apr 2026

PMID42014236 (opens in a new tab)DOI10.1016/j.mcn.2026.104091 (opens in a new tab)PepBankPUB-42014236
Publisher pagePubMedAsk about this study
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Summary

BackgroundThe incidence of Alzheimer's disease (AD) is increasing globally but there are limited effective therapies available. Recently, evidence has demonstrated a role of GLP-1 receptor (GLP-1R) agonists, commonly used in the treatment of type 2 diabetes, may have therapeutic potential in AD. GLP-1R agonists have exhibited their neuroprotective role by targeting tau hyperphosphorylation and the accumulation of beta-amyloid (Aβ) plaques. This systematic review aims to evaluate the effectiveness of liraglutide, semaglutide, exenatide and dulaglutide on AD pathology with a focus on the key biomarkers: hyperphosphorylated tau and Aβ.MethodsA systematic literature search was conducted using PubMed, Embase and Cochrane Library. Inclusion criteria involved pre-clinical and clinical studies investigating the effects of GLP-1 agonists dulaglutide, liraglutide, semaglutide or exenatide on Aβ and tau pathology. Randomised and non-randomised studies were included. Exclusion criteria involved studies evaluating GLP-1R agonists other than those specified.ResultsThis review examined thirty preclinical studies investigating the effects of four GLP-1 receptor agonists on Alzheimer's disease pathology, particularly Aβ plaque accumulation and tau hyperphosphorylation. Most studies focused on liraglutide, which consistently reduced both Aβ and tau pathology in animal and cell models. Dulaglutide, although studied less frequently, consistently reduced tau phosphorylation and Aβ accumulation in mouse models while also improving cognitive outcomes. Semaglutide also showed largely positive effects with four studies reporting reduced Aβ or tau pathology, though one study reported no benefit. Two clinical studies were also reviewed. A phase II trial of Exenatide showed reduced plasma Aβ42 in extracellular vesicles but not cognitive benefit. A smaller liraglutide trial demonstrated no reduction in Aβ burden or cognitive change though it preserved brain glucose metabolism. An EXSCEL trial showed significant changes in systemic inflammatory markers. While pre-clinical data has been encouraging, clinical evidence remains limited.ConclusionsThere is consistent preclinical evidence that GLP-1R agonists are effective in reducing Aβ levels and hyperphosphorylated tau. While the neuroprotective effect in preclinical studies is clear, clinical findings have so far failed to demonstrate an arresting effect on cognitive.RegistrationPROSPERO CRD420251029748.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. 3 results from people.

  1. 01HumanSystematic reviewEfficacy outcome

    In a smaller liraglutide trial reviewed, liraglutide showed no reduction in amyloid-beta burden.

    In plain wordsIn a small clinical trial, liraglutide did not reduce amyloid-beta burden.

    Peptide
    Liraglutide
    Outcome
    Not applicableAmyloid-beta burden
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    A smaller liraglutide trial demonstrated no reduction in Aβ burden or cognitive change though it preserved brain glucose metabolism.
    3 context sentences
    Summary · context
    A systematic literature search was conducted using PubMed, Embase and Cochrane Library.
    Summary · context
    Inclusion criteria involved pre-clinical and clinical studies investigating the effects of GLP-1 agonists dulaglutide, liraglutide, semaglutide or exenatide on Aβ and tau pathology.
    Summary · context
    Two clinical studies were also reviewed.
  2. 02HumanSystematic reviewEfficacy outcome

    In a smaller liraglutide trial reviewed, liraglutide showed no cognitive change.

    In plain wordsIn a small clinical trial, liraglutide did not change cognition.

    Peptide
    Liraglutide
    Outcome
    Not applicableCognitive change
    Study

    n: not reported in source

    Outcome group
    Cognition and memory · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    A smaller liraglutide trial demonstrated no reduction in Aβ burden or cognitive change though it preserved brain glucose metabolism.
    3 context sentences
    Summary · context
    A systematic literature search was conducted using PubMed, Embase and Cochrane Library.
    Summary · context
    Inclusion criteria involved pre-clinical and clinical studies investigating the effects of GLP-1 agonists dulaglutide, liraglutide, semaglutide or exenatide on Aβ and tau pathology.
    Summary · context
    Two clinical studies were also reviewed.
  3. 03HumanSystematic reviewEfficacy outcome

    In a smaller liraglutide trial reviewed, liraglutide preserved brain glucose metabolism.

    In plain wordsIn a small clinical trial, liraglutide preserved brain glucose metabolism.

    Peptide
    Liraglutide
    Outcome
    Not applicableBrain glucose metabolism
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    A smaller liraglutide trial demonstrated no reduction in Aβ burden or cognitive change though it preserved brain glucose metabolism.
    3 context sentences
    Summary · context
    A systematic literature search was conducted using PubMed, Embase and Cochrane Library.
    Summary · context
    Inclusion criteria involved pre-clinical and clinical studies investigating the effects of GLP-1 agonists dulaglutide, liraglutide, semaglutide or exenatide on Aβ and tau pathology.
    Summary · context
    Two clinical studies were also reviewed.
  4. 04AnimalOther designEfficacy outcome

    In animal and cell models reviewed, liraglutide consistently reduced amyloid-beta pathology.

    In plain wordsIn animal and cell models, liraglutide reduced amyloid-beta pathology.

    Peptide
    Liraglutide
    Outcome
    DecreaseAmyloid-beta pathology
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Most studies focused on liraglutide, which consistently reduced both Aβ and tau pathology in animal and cell models.
    3 context sentences
    Summary · context
    A systematic literature search was conducted using PubMed, Embase and Cochrane Library.
    Summary · context
    Inclusion criteria involved pre-clinical and clinical studies investigating the effects of GLP-1 agonists dulaglutide, liraglutide, semaglutide or exenatide on Aβ and tau pathology.
    Summary · context
    This review examined thirty preclinical studies investigating the effects of four GLP-1 receptor agonists on Alzheimer's disease pathology, particularly Aβ plaque accumulation and tau hyperphosphorylation.
  5. 05AnimalOther designEfficacy outcome

    In animal and cell models reviewed, liraglutide consistently reduced tau pathology.

    In plain wordsIn animal and cell models, liraglutide reduced tau pathology.

    Peptide
    Liraglutide
    Outcome
    DecreaseTau pathology
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Most studies focused on liraglutide, which consistently reduced both Aβ and tau pathology in animal and cell models.
    3 context sentences
    Summary · context
    A systematic literature search was conducted using PubMed, Embase and Cochrane Library.
    Summary · context
    Inclusion criteria involved pre-clinical and clinical studies investigating the effects of GLP-1 agonists dulaglutide, liraglutide, semaglutide or exenatide on Aβ and tau pathology.
    Summary · context
    This review examined thirty preclinical studies investigating the effects of four GLP-1 receptor agonists on Alzheimer's disease pathology, particularly Aβ plaque accumulation and tau hyperphosphorylation.
  6. 06AnimalOther designEfficacy outcome

    In preclinical studies reviewed, four semaglutide studies reported reduced amyloid-beta or tau pathology.

    In plain wordsIn preclinical studies, semaglutide reduced amyloid-beta or tau pathology in four studies.

    Peptide
    Semaglutide
    Outcome
    DecreaseAmyloid-beta or tau pathology
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Semaglutide also showed largely positive effects with four studies reporting reduced Aβ or tau pathology, though one study reported no benefit.
    3 context sentences
    Summary · context
    A systematic literature search was conducted using PubMed, Embase and Cochrane Library.
    Summary · context
    Inclusion criteria involved pre-clinical and clinical studies investigating the effects of GLP-1 agonists dulaglutide, liraglutide, semaglutide or exenatide on Aβ and tau pathology.
    Summary · context
    This review examined thirty preclinical studies investigating the effects of four GLP-1 receptor agonists on Alzheimer's disease pathology, particularly Aβ plaque accumulation and tau hyperphosphorylation.
  7. 07AnimalOther designEfficacy outcome

    In preclinical studies reviewed, one semaglutide study reported no benefit for amyloid-beta or tau pathology.

    In plain wordsIn preclinical studies, one semaglutide study found no benefit for amyloid-beta or tau pathology.

    Peptide
    Semaglutide
    Outcome
    Not applicableAmyloid-beta or tau pathology
    Study

    n: not reported in source

    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Semaglutide also showed largely positive effects with four studies reporting reduced Aβ or tau pathology, though one study reported no benefit.
    3 context sentences
    Summary · context
    A systematic literature search was conducted using PubMed, Embase and Cochrane Library.
    Summary · context
    Inclusion criteria involved pre-clinical and clinical studies investigating the effects of GLP-1 agonists dulaglutide, liraglutide, semaglutide or exenatide on Aβ and tau pathology.
    Summary · context
    This review examined thirty preclinical studies investigating the effects of four GLP-1 receptor agonists on Alzheimer's disease pathology, particularly Aβ plaque accumulation and tau hyperphosphorylation.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 3Current

    12 Oct 2026, 11:11 UTC

    Study results updated

  2. Version 2

    9 Oct 2026, 03:06 UTC

    Study data updated · source update from Europe PMC

  3. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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