A research study led by Seoul National University College of Medicine shows that sodium-glucose cotransporter-2 (SGLT-2) inhibitors could help prevent dementia in some people with type 2 diabetes.
The study, published in the BMJ, showed that compared to people taking an alternate diabetes drug known as a dipeptidyl peptidase-4 (DPP-4) inhibitor, people taking SGLT-2 inhibitors appeared to be 35% less likely to develop dementia over a follow-up period of around two years.
“According to a pooled analysis, type 2 diabetes is associated with a 60% greater risk of dementia, predisposing such people to both Alzheimer’s disease and vascular dementia,” wrote lead author Eun Ha Kang, a professor at Seoul National University Bundang Hospital, and colleagues.
“The mechanisms linking type 2 diabetes and dementia are multifactorial, involving insulin resistance, hypoglycemic episodes, and vascular compromise,” they explain.
People with type 2 diabetes are therefore an “at-risk” group for developing dementia and finding treatments that could help prevent or slow neurodegenerative symptoms is important.
Some previous research in older people (over the age of 65 years) has suggested that SGLT2 inhibitors could have a beneficial effect on dementia in people with type 2 diabetes. But whether this applies in younger people is less clear.
In this study, 110,885 matched pairs of people with type 2 diabetes, one of whom was taking a SGLT2 inhibitor and one a DPP-4 inhibitor, were included in the cohort. The age of the group was 40–69 years and none had dementia on recruitment.
Over an average of 670 days follow up, 1172 people in the group had a diagnosis of dementia. After correcting for possible confounding factors such as age, sex, use of metformin and cardiovascular risk at recruitment, those taking SGLT2 inhibitors had a 35% reduction in risk for a dementia diagnosis, and a 46% lower risk for having dementia needing drug treatment.
The risks for being diagnosed with Alzheimer’s disease and vascular dementia, respectively, were 39% and 52% less likely in the SGLT2 versus the DPP-4 inhibitor groups. Longer treatment with SGLT2 inhibitors also seemed to increase the benefit against dementia versus shorter treatment.
“Recent evidence suggests neuroprotective effects of SGLT-2 inhibitors based on penetration of the drug through the blood-brain barrier, SGLT-2 expression in brain tissue, and direct inhibition of acetylcholinesterase, as well as indirect cardiometabolic benefits,” suggested Kang and team.
The researchers caution that although the results are promising, the effect size seen in the study could be an overestimation due to its observational nature. They recommend that the results should be validated by other researchers. “Randomized controlled trials are needed to confirm these findings,” they emphasized.
