Sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase IV inhibitors and risk of dementia among patients with type 2 diabetes and comorbid mental disorders: A population-based cohort study

Aim: To evaluate whether the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors which have shown potential neuroprotective effects, is associated with lower risk of dementia in patients with type 2 diabetes (T2D) and comorbid mental disorders, who are considerably more susceptible to dementia. Methods: Using the nationwide healthcare data of South Korea between 2010 and 2022, we conducted a retrospective cohort study among patients with T2D and comorbid mental disorders initiating SGLT2 inhibitors versus active comparator (Dipeptidyl Peptidase IV (DPP4) inhibitors). Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years of incident dementia were estimated after weighting by propensity score fine stratification method. Results: Over a 4.8-year median follow-up, SGLT2 inhibitors were associated with a 12 % lower risk of dementia compared with DPP4 inhibitors (11.31 vs. 12.86 events per 1000 person years; HR 0.88, 95 % CI 0.84 to 0.92; RD -1.55, -2.13 to -0.97). The results were consistent when stratified by age, sex, individual component, severe mental disorders, presence of insulin, history of cardiovascular disease, or history of hypertension. Conclusions: SGLT2 inhibitors versus DPP4 inhibitors were associated with a lower risk of incident dementia in patients with T2D and comorbid mental disorders. Further randomized controlled trials are required to confirm our findings.