No clear link between SGLT-2 inhibitors and dementia

There appears to be no conclusive evidence to suggest that the use of sodium-glucose co-transporter-2 (SGLT-2) inhibitors may help reduce the risk of dementia, as shown in a population-based retrospective cohort study.

For the study, researchers used data from the Clinical Practice Research Datalink (CPRD) Aurum database from the UK. They looked at adults with type 2 diabetes who were at least 40 years of age, had received a new prescription of SGLT-2 inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors.

Incident dementia was the primary outcome, while incident mild cognitive impairment (MCI) was the secondary outcome. Cox proportional hazard models were used to examine the risk of the primary and secondary outcomes in relation to SGLT-2 vs DPP-4 inhibitor use.

The total study population consisted of 118,006 individuals, of which 34,816 initiated treatment with an SGLT-2 inhibitor and 83,190 with a DPP-4 inhibitor. Compared with DPP-4 inhibitor users, SGLT-2 inhibitor users tended to be younger (mean age 56.83 vs 62.34 years), obese (58.99 percent vs 45.26 percent), and have a higher HbA1c (>8 mmol/mol) level (70.65 percent vs 62.36 percent).

Dementia occurred at a rate of 0.56 per 1,000 person-years over a median follow-up of 1.54 years among SGLT-2 inhibitor users as opposed to 2.67 per 1,000 person-years over a median follow-up period of 1.79 years among DPP-4 inhibitor users.

The adjusted hazard ratio associated with SGLT-2 vs DPP-4 inhibitor use was 0.78 (95 percent confidence interval [CI], 0.55–1.12) for dementia and 0.86 (95 percent CI, 0.80–0.92) for MCI. In the age-specific stratified analysis, the adjusted HR for dementia associated with SGLT-2 vs DPP-4 inhibitor use was 0.50 (95 percent CI, 0.31–0.80) among older individuals (age ≥65 years).

The findings suggest that SGLT-2 inhibitor use may potentially reduce the risk of MCI among adults ≥40 years of age and that of dementia among those ≥65 years of age.