Thiazolidinedione May Reduce Risk of All-Cause Dementia in Adults with Type 2 Diabetes

Thiazolidinedione (TZD) monotherapy for type 2 diabetes (T2D) was associated with a 22% lower risk of all-cause dementia onset, according to the authors of a study published in BMJ Open Diabetes Research and Care. TZD dual therapies also showed a lower risk for all cause dementia and other disease subtypes.

“TZD users had a lower risk of dementia, and [sulphonylureas (SU)] users had a higher risk of dementia than [metformin (MET)] users among T2D participants. The protective effects of TZD were more substantial for overweight or obese patients,” wrote the study authors.

T2D is associated with an increased risk of all-cause dementia (subtypes include Alzheimer disease [AD] and vascular dementia [VaD]), which affects nearly 55 million people worldwide. Studies have linked antidiabetic medications like TZD and metformin (MET) with lowering risk of dementia in T2D patients on insulin—however the antidiabetic medication (ADM) SU was found to increase risk of dementia with insulin.

This study aimed to compare MET, SU, and TZD with dementia onset in veterans with T2D. The primary endpoint was a diagnosis of all-cause dementia at follow-up with 2 outpatient diagnosis codes apart by a minimum of 30 days, and secondary endpoints were VaD and AD with the same time and codes for diagnosis.

In total, the 19-year study looked at 559,106 eligible veterans who were assessed using a diverse array of biomarkers, including body mass index (BMI), lipid levels, and glycated hemoglobin measures. The mean time for follow-up was 6.8 years.

TZD was associated with decreased risk of AD by 11%, and all-cause dementia by 22%. It was also found to decrease risk of VaD as a monotherapy; the study authors explained that vascular diseases have the potential to increase the risk of AD, so TZD’s reduction in VaD may also reduce AD development.

Additionally, TZD deceased the all-cause risk of dementia as a combination therapy with MET or SU. However, SU as a monotherapy was found to work adversely—SU with daily insulin was associated with a 12% increased risk of developing onset all-cause dementia. SU was also associated with a 14% increased risk of contracting VaD.

After 1 year, the data also showed that the effects of TZD monotherapy were most significant among patients aged 75 years and younger, and patients who had a BMI greater than 25 kg. Adversely, SU was associated with a greater risk of dementia, especially among those with a higher BMI.

“Analysis based on ADM supply days also indicated that more consistent TZD use (as dual therapy with MET or as monotherapy) was [also] associated with lower risks of all-cause dementia,” study authors wrote in the report.

Reference

Tang, Xin, Brinton, Roberta, Chen, Zhao, et al. Use of oral diabetes medications and the risk of incident dementia in US veterans aged ≥60 years with type 2 diabetes. BMJ Open Diabetes Research and Care 2022;10:e002894. doi:10.1136/bmjdrc-2022-002894