Association between use of sodium-glucose co-transporter-2 inhibitor and the risk of incident dementia: a population-based cohort study.

OBJECTIVES

To assess the association between sodium-glucose co-transporter-2 inhibitor (SGLT-2i) use and the risk of incident dementia compared with dipeptidyl peptidase-4 inhibitors (DPP-4i) use among individuals with type 2 diabetes.

DESIGN

A population-based retrospective cohort study.

SETTING

The Clinical Practice Research Datalink (CPRD) Aurum database from the UK.

PARTICIPANTS

Individuals with type 2 diabetes, aged 40 years or older, newly prescribed SGLT-2i or DPP-4i on or after 2013-2021, registered in the CPRD Aurum database.

MAIN OUTCOME MEASURE

The primary outcome was incident dementia, and the secondary outcome was incident mild cognitive impairment (MCI). Cox proportional hazard models were used to estimate the HR and corresponding 95% CI for the primary and secondary outcomes. Propensity score fine stratification weights were used to adjust for confounding.

RESULTS

Among a cohort of 118 006 individuals, the incident rate (IR) of dementia was 0.56/1000 person-years over a median follow-up period of 1.54 years among SGLT-2i users compared with 2.67/1000 person-years in DPP-4i users, over a median follow-up period of 1.79 years. The adjusted HR for SGLT-2i use compared with DPP-4i use for dementia was 0.78 (95% CI 0.55 to 1.12), while for MCI was 0.86 (95% CI 0.80 to 0.92). The age-specific stratified analysis demonstrated the adjusted HR for SGLT-2i use compared with DPP-4i use for the risk of incident dementia among elderly, aged ≥65 years, was 0.50 (95% CI 0.31 to 0.80).

CONCLUSION

Primary findings did not yield conclusive evidence to infer an association between SGLT-2i use and the risk of incident dementia.