Risk of Dementia in Older Patients with Type 2 Diabetes on Dipeptidyl-Peptidase IV Inhibitors Versus Sulfonylureas: A Real-World Population-Based Cohort Study

Background: Type 2 diabetes is related to an increased risk of dementia. Preclinical studies of dipeptidyl peptidase-IV inhibitors (DPP-4i) for dementia have yielded promising results. Therefore, we investigated the risk of dementia in elderly patients with type 2 diabetes on DPP-4is and sulfonylureas (SU). Methods: Using a claims database called the Korean National Health Insurance Service Senior cohort, new users of DPP-4is and SUs were matched by 1:1 propensity score matching using 49 confounding variables (7552 new DPP-4is users and 7552 new SU users were matched by 1:1 propensity score matching; average age 75.4; mean follow-up period: 1361.9 days). Survival analysis was performed to estimate the risk of dementia. Results: The risk of all-cause dementia was lower in the DPP-4i group compared to the SU group (hazard ratio (HR) 0.66; 95% confidence interval (CI) 0.56–0.78; p < 0.001). Particularly, DPP-4i use showed a significantly lower risk of Alzheimer’s disease (HR 0.64; 95% CI 0.52–0.79; p < 0.001) and a lower risk, albeit non-significant, of vascular dementia compared to SU use (HR 0.66; 95% CI 0.38–1.14; p = 0.139). Conclusion: Our findings suggest that DPP-4i use decreases the risk of dementia compared to SU use in elderly patients with type 2 diabetes in a real-world clinical setting.