Evidence map›Paper›PMID 39445596›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024

Associations of semaglutide with first-time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US.

William Wang, QuangQiu Wang, Xin Qi, Mark Gurney, George Perry, Nora D Volkow, Pamela B Davis, David C Kaelber, Rong Xu

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 7 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

115 citing papers in PubMed, 7 syntheses or guidelines pooled it.

  1. A Systematic Review and Meta-Analysis of Semaglutide Effects on Adipose Tissue and Emerging Effects on Brain and Cognition.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026
    Pooled it
  2. Glucagon-like peptide-1 agonists in Parkinson's disease: a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Pooled it
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  8. Effects of Semaglutide on Cognitive Function in People With HIV: A Randomized, Controlled Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
    Trial
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  12. GLP-1R agonist semaglutide protects human forebrain organoids from cholesterol-induced neurotoxicity.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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55 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

William WangCenter for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
QuangQiu WangCenter for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Xin QiDepartment of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Mark GurneyCenter for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
George PerryCenter for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Nora D VolkowNational Institute on Drug Abuse, National Institutes of Health, Maryland, USA.
Pamela B DavisCenter for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
David C KaelberCenter for Clinical Informatics Research and Education, The MetroHealth System, Ohio, USA.
Rong XuCenter for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Funding

Clinical and Translational Science Collaborative of Northern Ohio, Catalyzing Linkages to Equity in Health (CLE Health)UM1TR004528 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI GRACE A MCCOMSEY · 2023 to 2026
$32.1M
Combine computational prediction, network analysis and genetic screening in C elegans to uncover neurodegenerative causes in Alzheimer's DiseaseR01AG061388 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI CHEN, SHU G., XU, RONG · 2018 to 2022
$3.4M
Mechanism of white matter pathology in Alzheimer's diseaseR01AG076051 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI XIN QI · 2022 to 2026
$3.0M
Role of brain lipid metabolism in Alzheimer's diseaseR01AG065240 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI QI, XIN · 2020 to 2024
$3.0M
An Integrated Reverse Engineering Approach Toward Rapid drug Re positioning for Alzheimer's DiseaseR01AG057557 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI XU, RONG · 2017 to 2021
$2.8M
Proteostasis dysregulation and alpha-synucleinR01NS115903 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI QI, XIN · 2020 to 2023
$2.4M
Collision of Alzheimers disease and COVID-19 pandemic in the United States: risks, outcomes, disparities and treatmentsRF1AG076649 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI DAVIS, PAMELA B, XU, RONG · 2022 to 2022
$2.3M
Regulation of CHCHD6 in Alzheimer's diseaseRF1AG074346 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI QI, XIN · 2022 to 2022
$2.1M
Construct large-scale phenomes of disease and drugs and develop data-driven systems approaches to understand genetic links between Alzheimer's disease and Neuropsychiatric symptomsR56AG062272 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI XU, RONG · 2018 to 2019
$1.6M
NCATS NIH HHS TR004528NCATS NIH HHS UM1 TR004528NIA NIH HHS AG057557 AG061388 AG062272 AG076649NIA NIH HHS R01 AG057557NIA NIH HHS R01 AG061388NIA NIH HHS R01 AG065240NIA NIH HHS R01 AG076051NIA NIH HHS R56 AG062272NIA NIH HHS RF1 AG074346NIA NIH HHS RF1 AG076649
6 · The paper itself

Abstract

introductionEmerging preclinical evidence suggests that semaglutide, a glucagon-like peptide receptor agonist (GLP-1RA) for type 2 diabetes mellitus (T2DM) and obesity, protects against neurodegeneration and neuroinflammation. However, real-world evidence for its ability to protect against Alzheimer's disease (AD) is lacking.

methodsWe conducted emulation target trials based on a nationwide database of electronic health records (EHRs) of 116 million US patients. Seven target trials were emulated among 1,094,761 eligible patients with T2DM who had no prior AD diagnosis by comparing semaglutide with seven other antidiabetic medications. First-ever diagnosis of AD occurred within a 3-year follow-up period and was examined using Cox proportional hazards and Kaplan-Meier survival analyses.

resultsSemaglutide was associated with significantly reduced risk for first-time AD diagnosis, most strongly compared with insulin (hazard ratio [HR], 0.33 [95% CI: 0.21 to 0.51]) and most weakly compared with other GLP-1RAs (HR, 0.59 [95% CI: 0.37 to 0.95]). Similar results were seen across obesity status, gender, and age groups. DISCUSSION: These findings support further studies to assess semaglutide's potential in preventing AD. HIGHLIGHTS: Semaglutide was associated with 40% to 70% reduced risks of first-time AD diagnosis in T2DM patients compared to other antidiabetic medications, including other GLP-1RAs. Semaglutide was associated with significantly lower AD-related medication prescriptions. Similar reductions were seen across obesity status, gender, and age groups. Our findings provide real-world evidence supporting the potential clinical benefits of semaglutide in mitigating AD initiation and development in patients with T2DM. These findings support further clinical trials to assess semaglutide's potential in delaying or preventing AD.

Indexed as

Alzheimer DiseaseDiabetes Mellitus, Type 2Glucagon-Like PeptidesHypoglycemic AgentsAgedAged, 80 and overFemaleHumansMaleMiddle AgedSemaglutideUnited StatesGlucagon-Like PeptidesHypoglycemic AgentsSemaglutideAlzheimer's diseaseemulation target trialpatient electronic health recordspreventionreal‐world datasemaglutidetype 2 diabetes

Identifiers

PMID39445596
PMCPMC11667504

What OpenQuestion holds

Texttitle and abstract
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.