Previously submitted to: Interactive Journal of Medical Research (no longer under consideration since Dec 19, 2024)
Date Submitted: Sep 12, 2024
Open Peer Review Period: Oct 8, 2024 - Dec 3, 2024
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Exploring SGLT2 Inhibitors’ Advantage Over Thiazolidinediones in Neurodegenerative Prevention: A Real-World Data Analysis
ABSTRACT
Background:
Dementia, especially Alzheimer's disease (AD), increases significantly with age. Type 2 diabetes mellitus (DM) is associated with a higher risk of cognitive decline and dementia. Emerging evidence suggests that certain antidiabetic medications may affect neurodegenerative outcomes.
Objective:
This study aimed to compare the risk of stroke, dementia, and AD between patients treated with sodium-glucose co-transporter 2 (SGLT2) inhibitors and those treated with thiazolidinediones (TZDs).
Methods:
This multicenter retrospective observational cohort study utilized electronic health records from 12 secondary and tertiary hospitals in South Korea from October 1, 2009, to April 30, 2023. Patients aged 55 years or older who were newly prescribed either SGLT2 inhibitors or TZDs without prior exposure were included. Incidence rates of stroke, dementia, and AD were evaluated using propensity score matching and Cox regression analysis to calculate hazard ratios (HRs).
Results:
The study included 31,998 cases of stroke, 33,942 cases of dementia, and 34,500 cases of AD. Compared to TZDs, the use of SGLT2 inhibitors significantly reduced the risk of stroke (HR 0.6248, 95% CI 0.4154–0.9398, P= .0024), dementia (HR 0.5622, 95% CI 0.4077–0.7751, P=.0004), and AD (HR 0.5556, 95% CI 0.3831–0.8056, P=.0019).
Conclusions:
SGLT2 inhibitors are associated with a reduced risk of stroke, dementia, and Alzheimer's disease compared to TZDs in patients aged 55 years and older with type 2 diabetes. These findings suggest a potential neuroprotective effect of SGLT2 inhibitors, which may inform therapeutic decision-making for type 2 DM patients at risk for neurodegenerative diseases. Further prospective studies are needed to validate these associations and elucidate the underlying mechanisms. Clinical Trial: Not applicable
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