new research suggests.
Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.
However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.
“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.
However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.
This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.
The results were published online in Neurology.
Dose-response relationship
Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.
This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.
Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.
Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.
Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.
There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).
A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
Several limitations
The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).
The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.
The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).
“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.
However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.
The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.
There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.