Objective: To compare the risk of dementia associated with sodium glucose co-transporter 2 inhibitor (SGLT2i) versus dipeptidyl peptidase 4 inhibitor (DPP4i) among relatively young patients with type 2 diabetes (T2DM) patients.
Methods: We conducted a population-based cohort study using 2010-2021 Korea National Health Insurance Service database on T2DM patients aged ≥40 and ≤70 years initiating SGLT2i versus DPP4i. The primary outcome was new onset dementia based on diagnosis codes. Secondary outcomes were dementia requiring medications, individual types of dementia, genital infection (positive control), and osteoarthritis encounter (negative control). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Fine-Gray models adjusting for competing risk of death, after a 1:1 ratio propensity-score (PS) matching for >110 potential baseline confounders. Subgroup analyses were done by age, sex, concurrent metformin use, and baseline cardiovascular risk.
Results: 110,885 PS-matched pairs of SGLT2i and DPP4i initiators were included. The mean follow-up time (standard deviation) were 670 days (650) with 1,172 new cases of dementia. The incidence rate was 0.22 in SGLT2i initiators and 0.35 in DPP4i initiators per 100 person-years, with the corresponding HR (95% CI) of 0.65 (0.57-0.73) for dementia, 0.57 (0.49-0.67) for dementia with medications, 0.63 (95% CI 0.55-0.72) for Alzheimer dementia, and 0.53 (95% CI 0.36-0.77) for vascular dementia. We observed a 2.45 times risk of genital infection with SGLT2i and near-null association for osteoarthritis encounter. The benefits were consistent across subgroups, and after accounting for lag times, but greater beyond than within 2 years of treatment.
Conclusion: Among patients with T2DM, SGLT2i may reduce the risk of dementia.
A. Shin: None. B. Koo: None. J. Lee: None. E. Kang: None.
This study was supported by the grant from the Korea Health Industry Development Institute (KHIDI)-AZ Diabetes Research Program (#08-2022-0261).
