Seoul, Korea—The use of thiazolidinediones to treat type 2 diabetes (T2D) declined significantly after a series of actions by the FDA. Those included communication on the potential cardiovascular risk of rosiglitazone and pioglitazone in 2007 and the requirement for a Risk Evaluation and Mitigation Strategy for rosiglitazone in 2010. The same year, the FDA also cautioned about the potential risk of bladder cancer with pioglitazone use.
Now, a new study from South Korea raised the possibility that patients with newly diagnosed T2D who take pioglitazone could lower their risk for developing dementia compared to those who did not.
The study, published in the journal Neurology, advised that results were most likely in those who also had a history of stroke or ischemic heart disease.
“Since dementia develops for years before diagnosis, there may be an opportunity for intervening before it progresses,” stated study author Eosu Kim, MD, PhD, of Yonsei University in Seoul, Republic of Korea. “These results may suggest that we could use a personalized approach to preventing dementia in people with diabetes in the case that they have a history of ischemic heart disease or stroke.”
The researchers looked at the national Korean health database for people newly diagnosed with T2D who did not have dementia. They were followed for an average of 10 years. Of the 91,218 participants, 3,467 received the drug pioglitazone.
During the study, 8.3% of the people taking pioglitazone developed dementia, compared with 10.0% of those who were not taking the drug. After researchers accounted for other factors that could affect dementia risk (e.g., high blood pressure, smoking, and physical activity), they found that people taking pioglitazone were 16% less likely to develop the disease than those who did not take it. The benefit was stronger among people who had a history of ischemic heart disease or stroke, with reduced risks of 54% and 43%.
The reduced risk also increased as people used the drug for longer periods. People who took the drug for 4 years were 37% less likely to develop dementia than those who did not take the drug, while those who took it for 1 to 2 years were 22% less likely.
People taking the drug were also less likely to have a stroke during the study.
Dr. Kim noted that side effects of pioglitazone include swelling, weight gain, bone loss, and congestive heart failure, and more research is needed on the long-term safety of the drug and whether there is an optimal dose that could minimize side effects while maintaining the benefits.
“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim stated. “In some previous studies of people with dementia or at risk of cognitive decline who did not have diabetes, pioglitazone did not show any protection against dementia, so it’s likely that a critical factor affecting the effectiveness is the presence of diabetes. More research is needed to confirm these findings.”
Background information in the article pointed out that previous studies have reported the protective effect of pioglitazone on dementia in type 2 diabetes mellitus (T2DM) patients. With recent studies also suggesting that pioglitazone also lowers the risk of primary and recurrent stroke, researchers posited that better understanding which patients benefit most could lead to more personalized use of pioglitazone.
To do that, the study team collection nationwide longitudinal data of T2DM patients from the Korean National Health Insurance Service DM cohort (2002-2017), investigating the association of pioglitazone use with incident dementia in patients with new-onset T2DM. The 91,218 participants were followed for an average of 10 years, with 3,467 of the study group receiving the drug pioglitazone.
The results indicated that pioglitazone use was associated with a reduced risk of dementia, compared with non-use (adjusted hazard ratio (HR) = 0.84; 95% CI, 0.75-0.95); the risk reduction in dementia was greater among patients with a history of ischemic heart disease or stroke before T2DM onset (adjusted HR = 0.46; 95% CI, 0.24-0.90 and adjusted HR = 0.57; 95% CI, 0.38-0.86, respectively).
“The incidence of stroke was also reduced by pioglitazone use (adjusted HR = 0.81; 95% CI, 0.66-1.00),” the researchers reported. “However, when the stroke developed during the observation period of pioglitazone use, such lowered risk of dementia was not observed (adjusted HR = 1.27; 95% CI, 0.80-2.04).”
The authors pointed out that 8.3% of the patients taking pioglitazone developed dementia, compared with 10.0% of those who were not using the drug. Considering other factors that could affect dementia risk (e.g., high blood pressure, smoking and physical activity), researchers determined that they found that pioglitazone appeared to reduce dementia risk by 16%. The effect was most pronounced in patients with a history of ischemic heart disease or stroke, with reduced risks of 54% and 43%.
The study concluded that pioglitazone use is associated with a lower risk of dementia in T2DM patients, especially in patients with a history of stroke or ischemic heart disease. That suggested that applying a personalized approach when choosing pioglitazone could help avoid dementia in some T2DM patients, according to the researchers.
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