Sodium-glucose Co-transporter 2 Inhibitors Lower the Risk for Dementia in Patients with Type 2 Diabetes Mellitus
Shih-Syuan Wang1, Steven Arnold2, Alvaro Pascual-Leone4, Pin-Chia Huang5, Kevin Sheng-Kai Ma3
1Department of Neurology, SUNY Downstate Medical Center, 2Department of Neurology, 3Department of Dermatology, Massachusetts General Hospital, 4Hinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Memory Health, Hebrew SeniorLife, 5Department of Epidemiology, Harvard T.H. Chan School of Public Health
Objective:
To assess the potential protective effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the onset of dementia, including vascular dementia (VaD), Alzheimer's disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB), in patients with type 2 diabetes mellitus (T2DM) compared to those treated with dipeptidyl peptidase-4 inhibitors (DPP4i).
Background:

Oral antidiabetic drugs (OADs) including metformin, dipeptidyl peptidase-4 inhibitor (DPP4i), and sodium-glucose cotransporter 2 inhibitors (SGLT2i) for type 2 diabetes mellitus (T2DM) have been explored in clinical trials as potential therapeutic candidates that may be repurposed for dementia. The aim of the present study was to investigate whether the use of SGLT2i may prevent dementia in patients with T2DM. 

Design/Methods:

This was a population-based cohort study that enrolled adult patients with T2DM from 92 hospitals across the United States. SGLT2i users were 1:1 propensity score matched to DPP4i users on demographics, comorbidities, co-medications, and healthcare utilization. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for new-onset dementia, vascular dementia (VaD), Alzheimer's disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). 

Results:

Before propensity score matching (PSM), a total of 1,977,424 patients with T2DM were included in the study, including 800,337 patients on SGLT2i and 1,177,087 patients on DPP4i. After PSM, 722,347 patients were included in the two arms, respectively. Patients with T2DM on SGLT2i presented with a significantly lower risk of new-onset dementia (HR: 0.56; 95% CI, 0.54-0.57), VaD (HR: 0.58; 95% CI, 0.54-0.61), AD (HR: 0.52; 95% CI, 0.49-0.54), FTD (HR: 0.68; 95% CI, 0.55-0.84), and DLB (HR 0.50; 95% CI, 0.42-0.60) compared to patients with T2DM on DPP4i.

Conclusions:

The use of SGLT2i for T2DM was associated with a significant reduction in the risk of dementia, VaD, AD, FTD, and DLB, compared with DPP4i. 

10.1212/WNL.0000000000205937