{
  "abstract": "Objective Type 2 diabetes mellitus has been associated with an increased risk of cognitive decline and dementia, with patients being 1.5–2 times more likely to develop these conditions. While both sodium-glucose co-transporter 2 (SGLT2) inhibitors and thiazolidinediones (TZDs) have shown potential neuroprotective effects in previous studies, their comparative effectiveness for preventing neurodegenerative outcomes has not been established. This study aimed to compare the risk of stroke, dementia and Alzheimer’s disease (AD) between patients treated with SGLT2 inhibitors and those treated with TZDs.Design Multicentre, retrospective, observational, new-user, active-comparator cohort study.Setting Electronic health record-based databases from 11 secondary and tertiary institutions in South Korea from 1 January 2014 to 31 July 2025. The study period began in 2014, following the post-marketing surveillance initiation of SGLT2 inhibitors in Korea (November 2013), to ensure adequate drug availability and clinical adoption.Participants Patients aged 40 years or older who were newly prescribed either SGLT2 inhibitors or TZDs without prior exposure.Interventions Propensity score matching (1:1) was performed using sex as the primary covariate due to data availability constraints in the Observational Medical Outcomes Partnership Common Data Model framework. The HRs with 95% CIs were measured via Cox regression analysis.Results The study analysed 24 172 matched pairs for stroke outcomes (40 483 person-years in the SGLT2 inhibitor group and 39 363 person-years in the TZD group), 25 111 matched pairs for dementia (41 924 person-years in the SGLT2 inhibitor group and 40 726 person-years in the TZD group) and 25 237 matched pairs for AD (42 139 person-years in the SGLT2 inhibitor group and 40 895 person-years in the TZD group) across 11 participating hospitals. After a 1:1 propensity score matching, the SGLT2 inhibitors showed no significant difference in stroke risk (HR 1.18, 95% CI 0.62 to 2.23, p=0.62), while having significant reductions in dementia risk (HR 0.66, 95% CI 0.45 to 0.98, p=0.04) and AD risk (HR 0.54, 95% CI 0.35 to 0.83, p=0.005). Moreover, these protective effects for neurodegenerative outcomes were shown to be consistent across multiple hospital sites.Conclusions SGLT2 inhibitors are associated with a reduced risk of dementia and AD compared with TZDs in patients aged 40 years or older with type 2 diabetes and have neutral effects on stroke risk. These findings confirm the potential selective neuroprotective benefits of SGLT2 inhibitors for neurodegenerative outcomes, which may inform therapeutic decision-making for diabetic patients at risk of cognitive decline.",
  "authors": [
    {
      "affiliations": [
        "Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"
      ],
      "name": "Sang Joon Park"
    },
    {
      "affiliations": [
        "Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"
      ],
      "name": "Hye Jeong Kim"
    },
    {
      "affiliations": [
        "Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"
      ],
      "name": "Mihae Seo"
    },
    {
      "affiliations": [
        "Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"
      ],
      "name": "Dong Won Byun"
    },
    {
      "affiliations": [
        "Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"
      ],
      "name": "Kyoil Suh"
    },
    {
      "affiliations": [
        "Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)",
        "Elim Thyroid Clinic, Seoul, Korea (the Republic of)"
      ],
      "name": "Myung Hi Yoo"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"
      ],
      "name": "Hyeon Yang"
    },
    {
      "affiliations": [
        "Informatization Project Department, Soonchunhyang University College of Medicine, Seoul, Korea (the Republic of)"
      ],
      "name": "Inho Lee"
    },
    {
      "affiliations": [
        "Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"
      ],
      "name": "Soon Hyo Kwon"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Soonchunhyang University Hospital Seoul, Yongsan-gu, Seoul, Korea (the Republic of)"
      ],
      "name": "Minjae Kim"
    },
    {
      "affiliations": [
        "Division of Endocrinology and Metabolism, Department of Internal Medicine, Soon Chun Hyang University Hospital Bucheon, Bucheon-si, Korea (the Republic of)"
      ],
      "name": "Ji-Oh Mok"
    },
    {
      "affiliations": [
        "Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Cheonan, Cheonan-si, Korea (the Republic of)"
      ],
      "name": "Dae-Yeon Kim"
    },
    {
      "affiliations": [
        "Division of Endocrinology and Metabolism, Department of Internal Medicine, Myongji Hospital, Goyang-si, Korea (the Republic of)"
      ],
      "name": "Seo Young Sohn"
    },
    {
      "affiliations": [
        "Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea (the Republic of)"
      ],
      "name": "Rae Woong Park"
    },
    {
      "affiliations": [
        "Internal Medicine, Kangdong Sacred Heart Hospital, Gangdong-gu, Korea (the Republic of)"
      ],
      "name": "Won-Woo Seo"
    },
    {
      "affiliations": [
        "Division of Endocrinology and Metabolism, Department of Internal Medicine, Daegu Catholic University Hospital, Daegu, Korea (the Republic of)"
      ],
      "name": "So Yoon Kwon"
    },
    {
      "affiliations": [
        "Department of Endocrinology and Metabolism, Kyung Hee University College of Medicine, Dongdaemun-gu, Korea (the Republic of)"
      ],
      "name": "Sang Youl Rhee"
    },
    {
      "affiliations": [
        "Department of Emergency Medicine, Sejong General Hospital, Bucheon-si, Korea (the Republic of)"
      ],
      "name": "Joon-Myoung Kwon"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Kyung Hee University Hospital at Gangdong, Gangdong-gu, Korea (the Republic of)"
      ],
      "name": "Jae Myung Cha"
    },
    {
      "affiliations": [
        "Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Yongsan-gu, Korea (the Republic of)"
      ],
      "name": "Hyeong Kyu Park"
    }
  ],
  "title": "Comparative risk of the neurodegenerative outcomes between sodium-glucose co-transporter 2 (SGLT2) inhibitors and thiazolidinediones in type 2 diabetes: a multicentre cohort study using the Korean healthcare database (2014–2025)",
  "uid": "9c779849-24d8-55f7-806e-b1ea6441f595"
}