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Cited by 180Diabetes Treatment and ManagementDementia and Cognitive Impairment ResearchAlzheimer's disease research and treatments

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

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Wang, William, Wang, QuangQiu, Qi, Xin, Gurney, Mark, Perry, George, Volkow, Nora D., Davis, Pamela B., Kaelber, David C. +1 more·2024·Alzheimer's & Dementia
DOI 10.1002/alz.14313PMC PMC11667504
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Abstract

INTRODUCTION: Emerging 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. METHODS: We 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. RESULTS: Semaglutide 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.

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  • The neuroprotection offered by GLP-1RAs may become more evident during later stages of cognitive decline.

    “Our findings align with previous studies supporting the neuroprotective potential of GLP-1RAs in dementia 30,46 but not in mild cognitive impairment, 6 suggesting that the neuroprotection offered by GLP-1RAs may become more evident during later stages of cognitive decline.”

    From Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity (2025) · cites this paper as [46]

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Authors
Wang, W., Wang, Q., Qi, X., Gurney, M., Perry, G., Volkow, N. D., Davis, P. B., Kaelber, D. C., & Xu, R.
Affiliations
  • Case Western Reserve University (US)
  • The University of Texas at San Antonio (US)
  • National Institutes of Health (US)
  • MetroHealth (US)
Corresponding author
Xu, Rong
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2024-10-24
Volume
20
Issue
12
Pages
8661-8672
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1002/alz.14313
PMC
PMC11667504
OpenAlex
W4403703331
Cited by
180
References
11
Citations by year
2026: 80 · 2025: 97 · 2024: 3
FWCI
59.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (AG057557 AG061388 AG062272 AG076649)
  • National Center for Advancing Translational Sciences (TR004528)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
semaglutide, Alzheimer's disease
MeSH terms
Semaglutide, Aged, Aged, 80 and over, Alzheimer Disease, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Female, Humans, Hypoglycemic Agents, Male, Middle Aged, United States

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