medwireNews: People aged 60 years or older receiving thiazolidinedione (TZD) monotherapy for type 2 diabetes may have a lower risk for dementia than those taking metformin monotherapy, an observational study suggests.
By contrast, monotherapy with a sulfonylurea was associated with a significantly increased dementia risk, report Jin Zhou (University of California, Los Angeles, USA) and co-researchers.
“Thus, monitoring cognitive functions regularly is more important to this population,” they write in BMJ Open Diabetes Research & Care.
Their study included Veterans Affairs Healthcare System data from 559,106 people with type 2 diabetes taking metformin, sulfonylureas, TZDs, or a combination, among whom the rate of dementia over an average follow-up of 6.8 years was 8.2 cases per 1000 person–years. The rate ranged from 6.2 cases per 1000 person–years in people taking metformin monotherapy to 13.4 per 1000 person–years in those taking TZDs and sulfonylureas in combination.
Zhou and team calculated the effects of 1 year of exposure to the medications of interest in an inverse probability treatment-weighted analysis with further adjustment for variables that remained unbalanced after weighting.
This revealed a significant reduction in the risk for all-cause dementia of 22% and 11% associated with TZD monotherapy and with the combination of TZD plus metformin, respectively, compared with metformin monotherapy, which the researchers note has no known association with dementia risk.
The association was stronger when examined across 2 years of treatment, and strengthened in line with more consistent medication taking, which Zhou and colleagues say “implies a dose–response relationship.”
About 8% of people with dementia had a specific diagnosis of vascular dementia, and use of TZD was associated with an approximately halved risk for this subtype, which the researchers believe “is consistent with the prior reports that TZDs can reduce carotid atherosclerosis and incident strokes.”
Conversely, there were significant increases in any dementia risk of 12% for people taking sulfonylurea monotherapy, 14% associated with sulfonylurea plus metformin, and 4% for sulfonylurea plus TZD.
In subgroup analyses, the team found that association of TZD with reduced dementia risk was significantly greater in people aged 75 years or younger than in older individuals, “perhaps highlighting the difficulty of successfully intervening in more advanced disease stages and the importance of early prevention for dementia.”
There was also a significantly stronger association among people who were overweight or obese than in those with a healthy BMI.
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BMJ Open Diabetes Res Care 2022; 10: e002894