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Evaluating GLP-1 receptor agonists versus metformin as first-line therapy for reducing dementia risk in type 2

Mingyang Sun1,2, Xiaoling Wang3,4, Zhongyuan Lu3,4

  • 1Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University Zhengzhou University，Henan Provincial People's Hospital, Zhengzhou, Henan, China zhangjiq@zzu.edu.cn szuyuanwu5399@gmail.com mingyangsun1986@163.com.

BMJ Open Diabetes Research & Care
|July 22, 2025
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show greater effectiveness than metformin in reducing dementia risk for type 2 diabetes patients. This includes lower risks of Alzheimer's disease and non-vascular dementias.

Area of Science:

  • Endocrinology and Metabolism
  • Neuroscience
  • Pharmacology

Background:

  • Type 2 diabetes mellitus (T2DM) is a risk factor for dementia.
  • No direct comparisons exist for GLP-1 RAs vs. metformin as first-line therapy for dementia prevention in T2DM.

Purpose of the Study:

  • To compare the effectiveness of GLP-1 RAs and metformin in reducing dementia risk in T2DM patients.
  • To assess the comparative efficacy of these antidiabetic agents for neuroprotection.

Main Methods:

  • Retrospective cohort study (2004-2024) using a global health network.
  • Included T2DM patients initiating GLP-1 RAs or metformin as first-line monotherapy.
  • Propensity score matching and Cox proportional hazards models were used.

Main Results:

  • GLP-1 RA use was linked to significantly lower risks of overall dementia (AHR 0.90), Alzheimer's disease (AHR 0.88), and non-vascular dementias (AHR 0.75) compared to metformin.
  • No significant difference was found for vascular dementia.
  • Benefits were consistent across subgroups, particularly in older adults and females.

Conclusions:

  • GLP-1 RAs demonstrate superior efficacy over metformin in mitigating dementia risk, especially AD and non-vascular types.
  • GLP-1 RAs may be a preferred first-line treatment for T2DM patients to reduce dementia incidence.
  • Randomized controlled trials are recommended for validation.
Keywords:
DementiaDiabetes Mellitus, Type 2Glucagon-Like Peptide 1Metformin

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