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Study · Observational study · n = 7,368 · 2026

3 results

Dulaglutide and neurodegeneration biomarkers: REWIND post hoc analysis.

Wilson JM, Dage JL, Qian HR, Irelan CL, Crowder HS, Duffin KL, Mintun M, Brooks DA, Gerstein HC, Bethel MA

Alzheimer's & dementia : the journal of the Alzheimer's Association1 Apr 2026Cited by 1 (Europe PMC)

PMID41988866 (opens in a new tab)PMCIDPMC13084528 (opens in a new tab)DOI10.1002/alz.71391 (opens in a new tab)PepBankPUB-41988866
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Summary

IntroductionThis post hoc analysis of the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial examined associations between dulaglutide, Alzheimer's disease and related dementia (ADRD) biomarkers, and substantive cognitive impairment (SCI).MethodsParticipants (dulaglutide, n = 3741; placebo, n = 3627) completed cognitive tests and provided blood samples at baseline and 2 years, with additional cognitive tests at 5-year and final visits. Analysis of covariance and Cox models tested associations between dulaglutide, SCI, and plasma neurofilament light chain (NfL), phosphorylated tau217 (p-tau217), and glial fibrillary acidic protein (GFAP) biomarkers.ResultsDulaglutide-associated changes in biomarkers or SCI were nonsignificant overall. Participants with NfL ≥56 pg/mL had a dulaglutide-associated 2-year reduction in NfL (-27.4% vs -14.2%; p = 0.003). Participants with p-tau217 ≥25 pg/mL had a dulaglutide-associated SCI reduction (hazard ratio = 0.78; p = 0.0064).DiscussionDulaglutide reduced NfL and SCI in participants with select elevated plasma ADRD biomarkers, with limited 2-year effects on p-tau217 and GFAP. Future studies with longer follow-up should explore incretin-related cognitive changes.Clinical trial registration informationNCT01394952, registered July 15, 2011.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

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

  1. 01HumanObservational studyEfficacy outcome

    In REWIND participants, dulaglutide showed no significant overall changes in ADRD biomarkers or substantive cognitive impairment versus placebo.

    In plain wordsIn trial participants, dulaglutide showed no significant overall difference from placebo in dementia-related biomarkers or substantial cognitive impairment.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    No significant changeOverall ADRD biomarkers and substantive cognitive impairment
    Study

    n = 7,368

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

    Source sentences

    Summary
    Dulaglutide-associated changes in biomarkers or SCI were nonsignificant overall.
    2 context sentences
    Summary · context
    Participants (dulaglutide, n = 3741; placebo, n = 3627) completed cognitive tests and provided blood samples at baseline and 2 years, with additional cognitive tests at 5-year and final visits.
    Summary · context
    Analysis of covariance and Cox models tested associations between dulaglutide, SCI, and plasma neurofilament light chain (NfL), phosphorylated tau217 (p-tau217), and glial fibrillary acidic protein (GFAP) biomarkers.
  2. 02HumanObservational studyEfficacy outcome

    In REWIND participants with baseline NfL ≥56 pg/mL, dulaglutide reduced NfL more than placebo at 2 years.

    In plain wordsIn participants with high NfL, dulaglutide reduced this nerve injury marker more than placebo.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    DecreaseNfL in participants with elevated baseline NfL
    Study

    n: not reported in source

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

    Measurements

    NfL change
    −27.4%
    dulaglutide, baseline NfL ≥56 pg/mL
    NfL change
    −14.2%
    placebo, baseline NfL ≥56 pg/mL

    Source sentences

    Summary
    Participants with NfL ≥56 pg/mL had a dulaglutide-associated 2-year reduction in NfL (-27.4% vs -14.2%; p = 0.003).
    2 context sentences
    Summary · context
    Participants (dulaglutide, n = 3741; placebo, n = 3627) completed cognitive tests and provided blood samples at baseline and 2 years, with additional cognitive tests at 5-year and final visits.
    Summary · context
    Analysis of covariance and Cox models tested associations between dulaglutide, SCI, and plasma neurofilament light chain (NfL), phosphorylated tau217 (p-tau217), and glial fibrillary acidic protein (GFAP) biomarkers.
  3. 03HumanObservational studyEfficacy outcome

    In REWIND participants with baseline p-tau217 ≥25 pg/mL, dulaglutide reduced substantive cognitive impairment versus placebo.

    In plain wordsIn participants with high p-tau217, dulaglutide reduced substantial cognitive impairment compared with placebo.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    DecreaseSubstantive cognitive impairment with elevated p-tau217
    Study

    n: not reported in source

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

    Measurements

    Hazard ratio
    0.78
    baseline p-tau217 ≥25 pg/mL

    Source sentences

    Summary
    Participants with p-tau217 ≥25 pg/mL had a dulaglutide-associated SCI reduction (hazard ratio = 0.78; p = 0.0064).
    2 context sentences
    Summary · context
    Participants (dulaglutide, n = 3741; placebo, n = 3627) completed cognitive tests and provided blood samples at baseline and 2 years, with additional cognitive tests at 5-year and final visits.
    Summary · context
    Analysis of covariance and Cox models tested associations between dulaglutide, SCI, and plasma neurofilament light chain (NfL), phosphorylated tau217 (p-tau217), and glial fibrillary acidic protein (GFAP) biomarkers.

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

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT01394952

Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND)

Eli Lilly and Companyn = 9,90122 Jul 2011 to 21 Aug 2018

Cardiovascular Disease · Diabetes Mellitus, Type 2

Trial pageClinicalTrials.govUpdated 8 Oct 2019

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 2Current

    22 Oct 2026, 02:25 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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