OBJECTIVES: To evaluate the impact of statins on delirium incidence in older adults with type 2 diabetes mellitus (T2DM), focusing on hydrophilic versus lipophilic statins and dose-response effects. DESIGN: Retrospective cohort study using propensity score matching and Cox regression analysis, with competing risk analysis to account for mortality. SETTING AND PARTICIPANTS: A total of 110,090 older adults (aged ≥65 years) with type 2 diabetes mellitus identified from Taiwan's National Health Insurance Research Database (2008-2021), including 55,045 statin users and 55,045 matched non-users. METHODS: Delirium incidence was compared between statin users and non-users, adjusting for potential confounders. Analyses evaluated the differential effects of hydrophilic and lipophilic statins and assessed the dose-response relationship using cumulative daily doses. RESULTS: Statin use significantly reduced delirium risk [adjusted hazard ratio (aHR), 0.73
95% confidence interval (CI), 0.67-0.79
P <
.0001]. Hydrophilic statins showed greater protection (aHR, 0.67
95% CI, 0.59-0.76) compared with lipophilic statins (aHR, 0.76
95% CI, 0.69-0.82). Higher cumulative doses were associated with greater risk reductions, with the highest dose quartile (Q4) demonstrating an aHR of 0.36 (95% CI, 0.30-0.43). The incidence rate ratio (IRR) was 0.70 (95% CI, 0.65-0.76
P <
.0001). CONCLUSIONS AND IMPLICATIONS: Statins, particularly hydrophilic types and higher doses, significantly reduce delirium risk in older adults with type 2 diabetes mellitus. These findings support statins' role in mitigating cognitive decline and improving outcomes in this population, with implications for clinical practice and future research.