Comparative effects of SGLT2 inhibitors, pioglitazone, DPP-4 inhibitors, and sulfonylureas on dementia risk in type 2 diabetes

Introduction Dementia risk is significantly amplified by type 2 diabetes (T2D). This study compares the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2is) against pioglitazone, dipeptidyl peptidase-4 inhibitors (DPP-4is), and sulfonylureas on dementia risk. Methods Using Taiwan’s National Health Insurance Research Database (2000–2021), researchers emulated target trials with propensity-score matching. Cox proportional-hazards and Kaplan-Meier analyses estimated adjusted hazard ratios (aHRs) for dementia subtypes. Results Over a mean follow-up of 2.9 years, SGLT2i users had significantly lower cumulative incidences of all-cause and vascular dementia (all log-rank p < 0.05). Compared to pioglitazone, SGLT2i use was associated with lower risks of all-cause dementia (aHR 0.78, 95% CI 0.73–0.83) and vascular dementia (aHR 0.83, 95% CI 0.69–0.99). Alzheimer's risk reductions were not statistically significant. Discussion In these nationwide emulated trials, SGLT2is were associated with lower risks of all-cause and vascular dementia compared with pioglitazone, DPP-4is, and sulfonylureas.