Calhoun and colleagues wrote that several studies have also shown no link between pioglitazone and bladder cancer. But a potential mechanistic link exists. Pioglitazone and a sister drug rosiglitazone (Avandia) are peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonists -- and this nuclear transcription factor is overexpressed in bladder tumors.
The researchers looked at data from about 1 million patients from British Columbia, Finland, Manchester, Rotterdam, Scotland, and the U.K. Clinical Practice Research Datalink, finding a total of 3,248 cases of bladder cancer.
They found no evidence of an association between bladder cancer and 100 days of cumulative exposure to pioglitazone in either men or women:
Men: RR 1.01, 95% CI 0.97 to 1.06
Women: RR 1.04, 95% CI 0.97 to 1.11
Nor was there any association between rosiglitazone and bladder cancer in either gender, they reported.
In a statement, the researchers said their analysis "is the only one to use identical methodology across international centers involving a large number of diabetic patients," but they still called for further research to "fully resolve this controversy."
The study was supported by the European Federation for the Study of Diabetes.
Colhoun reported financial relationships with Roche, Pfizer, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Sanofi, and Novartis.
Primary source: Diabetologia Source reference: Levin D, et al "Pioglitazone and bladder cancer risk: A multipopulation pooled cumulative exposure analysis" Diabetologia 2014; DOI: 10.1007/s00125-014-3456-9.