SGLT2 Inhibitors Reduce the Risk for Dementia, PD in Patients With Diabetes

Sodium-glucose cotransporter 2 (SGLT2) inhibitor use is associated with a significantly reduced risk for neurodegenerative disorders in individuals with type 2 diabetes, according to findings published in Neurology.

Researchers in South Korea conducted a retrospective cohort study to explore the relationship between SGLT2 inhibitor use (ie, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin) and risks for incident dementia and Parkinson disease (PD) in patients with type 2 diabetes. Participants in the Korean National Health Insurance Database with type 2 diabetes aged 40 and older who started antidiabetic drugs between September 2014 and December 2019 were eligible for inclusion. Individuals taking SGLT2 inhibitors were propensity score matched 1:1 with those taking other oral antidiabetic drugs. Primary outcomes included incidence of Alzheimer disease (AD), vascular dementia, and PD. To examine the association between SGLT2 inhibitor use and risks for dementia and PD, Cox proportional hazards models were used.

A total of 179,431 matched pairs (mean age, 57.8; men, 58.0%) were included in the study. The mean duration of follow-up was 2.06 years  for SGLT2 inhibitor users and 3.70 years for nonusers.

Overall, 6837 cases of incident dementia from any cause or PD were observed during 1,034,932 person-years of follow-up (incidence, 66.1/10,000 person-years). SGLT2 inhibitor use was associated with a significantly decreased risk for AD (adjusted hazard ratio [aHR], 0.81; 95% CI, 0.76-0.87), vascular dementia (aHR, 0.69; 95% CI, 0.60-0.78), and PD (aHR, 0.80; 95% CI, 0.69-0.91) with a 6-month drug use lag period.

Secondary composite outcome analysis revealed that SGLT2 inhibitor use vs use of other oral antidiabetic drugs was associated with a 21% lower risk for all-cause dementia (aHR, 0.79; 95% CI, 0.69-0.90) and a 22% lower risk for all-cause dementia and PD (aHR, 0.78; 95% CI, 0.73-0.83) with a 6-month exposure lag.

In sensitivity analyses, thiazolidinedione use vs nonuse of either SGLT2 inhibitors or thiazolidinedione was not significantly related to a lower risk for all-cause dementia and PD (aHR, 1.04; 95% CI, 0.92-1.18; P =.502) with a 6-month drug use lag period; SGLT2 inhibitor use, however, was significantly associated with a lower risk for all-cause dementia and PD (aHR, 0.76; 95% CI, 0.71-0.83).

The reduced risk for dementia and PD associated with SGLT2 inhibitor use was not impacted by sex, Charlson Comorbidity Index, diabetic complications, comorbidities, or use of antidiabetic medications, according to subgroup analyses (all interactions, P >.05).

Study limitations include potential misclassification and undetected outcomes of interest, short duration of follow-up, inability to identify various combination therapies, lack of biochemical parameter data, and reduced generalizability of results to a more diverse patient population.

“These findings suggest that SGLT2is may offer neurologic benefits among patients with type 2 diabetes, although additional studies are required to validate the long-term stability of these observations,” the study authors concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.