{
  "abstract": "Introduction No direct comparisons have evaluated glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus metformin as first-line antidiabetic therapy for preventing dementia in patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the comparative effectiveness of GLP-1 RAs and metformin in reducing dementia risk.Research design and methods This retrospective cohort study used data from a global health research network between 2004 and 2024. Patients with T2DM initiating GLP-1 RAs or metformin as first-line monotherapy were included. Propensity score matching was employed to balance baseline characteristics. Dementia incidence was analyzed using Cox proportional hazards models, with sensitivity analyses to confirm robustness.Results Among 87,229 matched patients per cohort, GLP-1 RA use was associated with a significantly lower risk of overall dementia (adjusted HR (AHR) 0.90; 95% CI 0.85 to 0.95), Alzheimer’s disease (AD) (AHR 0.88; 95% CI 0.83 to 0.94), and non-vascular dementias (non-VaDs) (AHR 0.75; 95% CI 0.70 to 0.81) compared with metformin. No significant difference was observed for VaD. Subgroup analyses showed consistent benefit across age and sex, with the strongest effect among older adults and females.Conclusions GLP-1 RAs were more effective than metformin in reducing the risk of dementia—especially AD and non-vascular types—highlighting their potential as a preferred first-line treatment in T2DM. Further randomized trials are warranted to validate these findings.",
  "authors": [
    {
      "affiliations": [
        "Department of Anesthesiology and Perioperative Medicine, People’s Hospital of Zhengzhou University Zhengzhou University，Henan Provincial People’s Hospital, Zhengzhou, Henan, China",
        "Institute of Electrophysiology, Henan Academy of Innovations in Medical Science, Zhengzhou, China"
      ],
      "name": "Mingyang Sun"
    },
    {
      "affiliations": [
        "Department of Anesthesiology and Perioperative Medicine, People’s Hospital of Zhengzhou University Zhengzhou University，Henan Provincial People’s Hospital, Zhengzhou, Henan, China",
        "Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China"
      ],
      "name": "Xiaoling Wang"
    },
    {
      "affiliations": [
        "Department of Anesthesiology and Perioperative Medicine, People’s Hospital of Zhengzhou University Zhengzhou University，Henan Provincial People’s Hospital, Zhengzhou, Henan, China",
        "Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China"
      ],
      "name": "Zhongyuan Lu"
    },
    {
      "affiliations": [
        "Department of Anesthesiology and Perioperative Medicine, People’s Hospital of Zhengzhou University Zhengzhou University，Henan Provincial People’s Hospital, Zhengzhou, Henan, China"
      ],
      "name": "Yitian Yang"
    },
    {
      "affiliations": [
        "Department of Anesthesiology and Perioperative Medicine, People’s Hospital of Zhengzhou University Zhengzhou University，Henan Provincial People’s Hospital, Zhengzhou, Henan, China"
      ],
      "name": "Shuang Lv"
    },
    {
      "affiliations": [
        "Department of Anesthesiology and Perioperative Medicine, People’s Hospital of Zhengzhou University Zhengzhou University，Henan Provincial People’s Hospital, Zhengzhou, Henan, China"
      ],
      "name": "Mengrong Miao"
    },
    {
      "affiliations": [
        "Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan",
        "Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei, Taiwan",
        "Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan"
      ],
      "name": "Wan-Ming Chen"
    },
    {
      "affiliations": [
        "Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei, Taiwan",
        "Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei, Taiwan",
        "Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan",
        "Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan, Taiwan",
        "Division of Radiation Oncology, Lo-Hsu Medical Foundation,Lotung Poh-Ai Hospital, Yilan, Taiwan",
        "Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan"
      ],
      "name": "Szu Yuan Wu"
    },
    {
      "affiliations": [
        "Department of Anesthesiology and Perioperative Medicine, People’s Hospital of Zhengzhou University Zhengzhou University，Henan Provincial People’s Hospital, Zhengzhou, Henan, China",
        "Institute of Electrophysiology, Henan Academy of Innovations in Medical Science, Zhengzhou, China"
      ],
      "name": "Jiaqiang Zhang"
    }
  ],
  "title": "Evaluating GLP-1 receptor agonists versus metformin as first-line therapy for reducing dementia risk in type 2 diabetes",
  "uid": "8edcd19a-e415-5b6f-988e-c4729465e41a"
}