PHOENIX, AZ — The risk of dementia, including Alzheimer’s disease, appeared to be reduced in veterans prescribed an older class of type 2 diabetes drugs, glitazones.
Use of the drugs, also known as thiazolidinediones (TZDs) was linked to a 22% reduced risk of dementia, according to a long-term study published in the open-access journal BMJ Open Diabetes Research & Care.1
Researchers from the University of Arizona and the Phoenix VA Healthcare System suggested those drugs might effectively prevent dementia in patients at high risk with mild or moderate type 2 diabetes. They posited that the drug class might be worth prioritizing in future clinical studies to see if they can be repurposed.
To study compared dementia risk in older people with type 2 diabetes treated with either a sulfonylurea or a thiazolidinedione (TZD) with those treated with metformin alone. To do that, the team collected data from 559,106 veterans with T2D in the VA health system from January 2000 to December 2019.
Included were 559,106 patients 60 and older who had been given a first prescription of metformin, or a sulfonylurea (tolbutamide, glimepiride, glipizide, or glyburide), or a TZD (rosiglitazone or pioglitazone) between January 2001 and December 2017. They were tracked for an average of nearly 8 years.
Results indicated that after at least one 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, among the participants with an average age of 65.7, the all-cause dementia rate was 8.2 cases per 1000 person-years (95% CI 6.0 to 13.7). After at least 1 year of treatment, TZD monotherapy was associated with a 22% lower risk of all-cause dementia onset (HR 0.78, 95% CI 0.75 to 0.81), compared with MET monotherapy, and 11% lower for MET and TZD dual therapy (HR 0.89, 95% CI 0.86 to 0.93), whereas the risk was 12% higher for SU monotherapy (HR 1.12 95% CI 1.09 to 1.15).
The authors pointed out that, the TZD drug class was associated with an 11% lower risk of Alzheimer’s disease and a 57% lower risk of vascular dementia. Researchers noted that, because vascular diseases increase the risk of Alzheimer’s disease, TZDs might be beneficial because of favorable effects on the vascular system.
The study advised that, 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. That prompted researchers to suggest that supplementing a sulfonylurea with either metformin or a TZD may partially offset these effects.
Further analysis found that patients younger than 75 benefited more from a TZD than older patients, and that the drugs appeared to be more protective in overweight or obese patients.
“These findings may help inform medication selection for [older] patients with [type 2 diabetes] at high risk of dementia,” the authors concluded.”
- Tang X, Brinton RD, Chen Z, Farland LV, Klimentidis Y, Migrino R, Reaven P, Rodgers K, Zhou JJ. Use of oral diabetes medications and the risk of incident dementia in US veterans aged ≥60 years with type 2 diabetes. BMJ Open Diabetes Res Care. 2022 Sep;10(5):e002894. doi: 10.1136/bmjdrc-2022-002894. PMID: 36220195; PMCID: PMC9472121.
