a new observational study in patients with type 2 diabetes suggests.
The data, obtained from nationwide electronic medical records from the Department of Veterans Affairs, yielded a 22% lower risk of dementia with TZD monotherapy and a 12% elevated risk with sulfonylurea monotherapy, compared with metformin monotherapy. The apparent protective effects of TZDs were greater among individuals with overweight or obesity.
“Our findings provide additional information to aid clinicians’ selection of [glucose-lowering medications] for patients with mild or moderate type 2 diabetes and [who] are at high risk of dementia,” Xin Tang and colleagues wrote in their article, published online in BMJ Open Diabetes Research & Care.
The results “add substantially to the literature concerning the effects of [glucose-lowering medications] on dementia where previous findings have been inconsistent. Studies with a follow-up time of less than 3 years have mainly reported null associations, while studies with longer a follow-up time typically yielded protective findings. With a mean follow-up time of 6.8 years, we had a sufficient duration to detect treatment differences,” the investigators wrote.
“Supplementing [a] sulfonylurea with either metformin or [a] TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia,” they added.
Randomized trials needed to determine cause and effect
Ivan Koychev, PhD, a senior clinical researcher in the department of psychiatry at the University of Oxford (England), told the UK Science Media Centre: “This is a large, well-conducted real-world data study that highlights the importance of checking whether already prescribed medications may be useful for preventing dementia.”
The findings regarding TZDs, also known as glitazones, are in line with existing literature suggesting dementia protection with other drugs prescribed for type 2 diabetes that weren’t examined in the current study, such as newer agents like glucagonlike peptide–1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, Dr. Koychev said.
“The main limitations of this study is that following the initial 2-year period the authors were interested in, the participants may have been prescribed one of the other type 2 diabetes drugs [GLP-1 agonists or SGLT2 inhibitors] that have been found to reduce dementia risk, thus potentially making the direct glitazone [TZD] effect more difficult to discern,” Dr. Koychev noted.
And, he pointed out that the study design limits attribution of causality. “It is also important to note that people with type 2 diabetes do run a higher risk of both dementia and cognitive deficits and that these medications are only prescribed in these patients, so all this data is from this patient group rather than the general population.”
James Connell, PhD, head of translational science at Alzheimer’s Research UK, agreed. “While this observational study found that those with type 2 diabetes taking thiazolidinedione had a lower dementia risk than those on the most common medication for type 2 diabetes, it only shows an association between taking the drug and dementia risk and not a causal relationship.
“Double-blind and placebo-controlled clinical trials are needed to see whether the drug [TDZ] could help lower dementia risk in people with and without diabetes. Anyone with any questions about what treatments they are receiving should speak to their doctor,” he told the UK Science Media Centre.