A study published in "BMJ Open Diabetes Research and Care" showed that in contrast to metformin (MET)-exclusive therapy, thiazolidinedione (TZDs) monotherapy was related with a 22% decrease in dementia risk while sulfonylurea (SU) monotherapy was associated with a 12% raised risk of dementia. Researchers aimed to compare the probability of dementia development in type 2 diabetes (T2D) patients receiving SU or TZD to those receiving MET.

This was a prospective observational study employing electronic medical records from all Veterans Affairs Healthcare System locations within a T2D population. Patients with T2D who started using antidiabetic medications, were ≥60 years at the time, and did not have dementia were included. Based on prescription data, control group (MET monotherapy), a TZD monotherapy group, and a SU monotherapy group were created.

The allocated therapy had to be taken by patients for a minimum of 1 year. All-cause dementia was the major endpoint, while vascular dementia and Alzheimer's disease were the 2 secondary endpoints. Propensity score weighted Cox proportional hazard models were used to compare the risks of developing outcomes. The rate of all-cause dementia was 8.2 cases per 1000 person-years among 559106 eligible veterans (mean age 65.7 [SD 8.7] years).

Following at least one year of therapy, TZD monotherapy was linked with a 22% minimized risk of all-cause dementia onset (HR 0.78), when compared to MET monotherapy, and 11% minimized risk for TZD and MET dual therapy (HR 0.89). However, there was a 12% greater risk for SU monotherapy (HR 1.12). Patients with T2D who used TZD had a decreased risk of dementia, but those who used SU had a greater risk than those who used MET. Adding MET or TZD to SU may help reduce the prodementia effects of the drug. The selection of medications for senior T2D patients who are at high risk of dementia may be influenced by these findings.