Associations of semaglutide with Alzheimer's disease-related dementias in patients with type 2 diabetes: A real-world target trial emulation study

Jun 24, 2025Journal of Alzheimer's disease : JAD

Semaglutide use and its link to Alzheimer's-related dementias in people with type 2 diabetes

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Abstract

Semaglutide is associated with a significantly reduced risk of overall Alzheimer's disease-related dementia (ADRD) incidence among patients with type 2 diabetes.

A hazard ratio of 0.54 indicates a lower risk of ADRD when comparing semaglutide to insulin.
Compared to metformin, semaglutide is associated with a hazard ratio of 0.67 for ADRD risk.
When compared to older generation glucagon-like peptide-1 agonists, the hazard ratio for ADRD risk with semaglutide is 0.80.
The reduced risk is particularly significant for vascular dementia, while no associations were found for frontotemporal and Lewy body dementias.
Findings suggest potential protective effects of semaglutide against dementia in patients with type 2 diabetes.

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BackgroundAlmost half of the dementia cases are preventable. Semaglutide treats several medical conditions that are risk factors for dementia.ObjectiveWe aim to investigate if semaglutide is associated with a decreased risk of dementia.MethodsWe conducted emulation target trials based on a nationwide population-based database of patient electronic health records (EHRs) in the US among 1,710,995 eligible patients with type 2 diabetes (T2D) comparing semaglutide with other antidiabetic medications. First-time diagnosis of Alzheimer's disease-related dementia (ADRD) including vascular dementia, frontotemporal dementia, Lewy body dementia and other dementias were examined using Cox proportional hazards and Kaplan-Meier survival analyses during a 3-year follow-up. Models were adjusted by propensity-score matching.ResultsWe show that semaglutide was associated with a significantly reduced risk of overall ADRD incidence with a hazard ratio ranging from 0.54 (0.49-0.59) compared with insulin, 0.67 (0.61-0.74) compared with metformin, to 0.80 (0.72-0.89) compared with older generation glucagon-like peptide-1 agonists (GLP-1RAs). The association varied for specific dementia types, with significantly reduced risk of vascular dementia and no evidence of associations with frontotemporal and Lewy body dementias.ConclusionsThese findings provide evidence supporting protective effects of semaglutide on dementias in patients with T2D. Future works are needed to establish the causal relationships through randomized clinical trials and to characterize the underlying mechanisms.

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Associations of semaglutide with Alzheimer's disease-related dementias in patients with type 2 diabetes: A real-world target trial emulation study

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