Patients With Diabetes Taking Pioglitazone Less Likely to Develop Dementia


Not only were people with newly diagnosed type 2 diabetes less likely to develop dementia if they took pioglitazone, but the benefit was stronger among patients with a history of ischemic heart disease or stroke.

People with newly diagnosed type 2 diabetes (T2D) who took the diabetes drug pioglitazone (Actos) were less likely to later develop dementia than those who did not take the drug, according to new research.

Researchers from the Republic of Korea found that use of pioglitazone was associated with a lower risk of dementia particularly in patients with T2D who had a history of stroke or ischemic heart disease. The findings were published in Neurology.1

“Since dementia develops for years before diagnosis, there may be an opportunity for intervening before it progresses,” study author Eosu Kim, MD, PhD, of Yonsei University in Seoul, Republic of Korea, said in a news release.2 “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 study does not prove that the drug reduces the risk of dementia for people with diabetes; it only shows an association, the American Academy of Neurology said in the news release.

Kim and colleagues examined data from the Korean National Health Insurance Service database for people newly diagnosed with T2D who did not have dementia and were followed for an average of 10 years. Of the 91,218 participants, 3467 received the drug pioglitazone.

During the study, 8.3% of the people taking pioglitazone developed dementia, compared with 10% of those who were not taking the drug. After researchers accounted for other factors that could affect dementia risk, such as 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%, respectively.

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.

However, the side effects of pioglitazone include swelling, weight gain, bone loss and congestive heart failure, Kim wrote, noting that additional 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,” Kim said. “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.”

The study was supported by the Korean Ministry of Health and Welfare and the National Research Foundation of Korea.


1. Ha J, Woo Choi D, Kim, et al. Pioglitazone use and reduced risk of dementia in patients with diabetes mellitus with a history of ischemic stroke. Published online February 15, 2023. doi:10.1212/WNL.0000000000207069

2. Drug linked to lower risk of dementia in people with diabetes. News release. American Academy of Neurology. February 15, 2023. Accessed February 16, 2023.

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