Diabetes Drug Linked to a Decreased Risk of Dementia

According to the scientists, it could be worthwhile to prioritize these drugs for future repurposing research.

According to a long-term study recently published in the open-access journal BMJ Open Diabetes Research & Care, using the diabetes drug known as glitazones is associated with a 22% lower risk of dementia. Glitazones are often known as thiazolidinediones or TZDs for short and are an older class of type 2 diabetes drugs.

According to the researchers, these drugs may effectively prevent dementia in high-risk individuals with mild to moderate type 2 diabetes, and it may now be worthwhile to give them priority in future clinical trials to determine whether they can be repurposed. 

Researchers have begun to investigate whether diabetes drugs could potentially help prevent or cure dementia since type 2 diabetes and dementia share several physiological patterns. However, the results have been inconsistent thus far.

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The researchers compared the incidence of dementia in older adults with type 2 diabetes who were receiving either sulfonylurea or thiazolidinedione (TZD) with those receiving metformin alone in order to shed further light on this.

They used data from 559,106 individuals with type 2 diabetes who had been diagnosed in the national Veteran Affairs (VA) Health System between January 2000 and December 2019.

Only older patients (aged at least 60) and given a first prescription of metformin, a sulfonylurea (tolbutamide, glimepiride, glipizide, or glyburide), or a TZD (rosiglitazone or pioglitazone) between January 2001 and December 2017 were included (559,106) in the study. Their health was tracked for an average of nearly 8 years.

After at least 1 year of drug treatment, the use of a TZD alone was associated with a 22% lower risk of dementia from any cause, compared with the use of metformin alone.

Specifically, it was associated with an 11% lower risk of Alzheimer’s disease and a 57% lower risk of vascular dementia. Given that vascular diseases increase the risk of Alzheimer’s disease, TZDs may also help to reduce dementia and Alzheimer’s disease in part through their favorable effects on the vascular system, say the researchers.

While the risk of dementia from any cause was 11% lower for the use of metformin and TZD combined, it was 12% higher for the use of a sulfonylurea drug alone, prompting the researchers to suggest that supplementing a sulfonylurea with either metformin or a TZD may partially offset these effects.

Further in-depth analysis indicated that those younger than 75 benefited more from a TZD than older patients, highlighting the importance of early prevention for dementia, note the researchers. And these drugs also seemed to be more protective in overweight or obese patients.

This is an observational study, so definitive conclusions can’t be drawn about cause and effect. And the researchers acknowledge that certain potentially influential information wasn’t available, including kidney function and genetic factors, and that study participants were predominantly male and White.

But they suggest that future studies for repurposing diabetes drugs for dementia prevention might want to consider prioritizing TZDs, based on their findings.

And they conclude: “These findings may help inform medication selection for [older] patients with [type 2 diabetes] at high risk of dementia.”

Reference: “Use of oral diabetes medications and the risk of incident dementia in US veterans aged ≥60 years with type 2 diabetes” by Xin Tang, Roberta Diaz Brinton, Zhao Chen, Leslie V. Farland, Yann Klimentidis, Raymond Migrino, Peter Reaven, Kathleen Rodgers and Jin J Zhou, 11 October 2022, BMJ Open Diabetes Research & Care.
DOI: 10.1136/bmjdrc-2022-002894

The study was funded by the National Human Genome Research Institute, the National Science Foundation, the National Institute of Diabetes and Digestive and Kidney Disease, and the National Heart, Lung, and Blood Institute.