The cumulative use of pioglitazone or rosiglitazone to treat type 2 diabetes was not associated with bladder cancer in a pooled analysis of six populations, according to research published in Diabetologia.

“These data challenge the idea that pioglitazone causes bladder cancer,”Helen Colhoun, MD, of the University of Dundee, United Kingdom, toldEndocrine Today. “We find no evidence of such an effect, at least in the time span of the study we have conducted, which was longer than many previously published.”

Helen Colhoun

Colhoun, with Daniel Levin, MD, also of the University of Dundee, and colleagues examined drug effects on bladder cancer risk using data from British Columbia, Finland, Manchester, Rotterdam, Scotland and UK Clinical Practice Research Datalink.

The investigators gathered prescription, cancer and mortality data from patients with type 2 diabetes. Data collected from six centers included 1.01 million patients during 5.9 million person-years; the mean age of the patients at entry into the centers was 60 to 64 years.

To model the effect of cumulative exposure on cancer incidence, a discrete time failure analysis was applied separately to data from each center with Poisson regression; time-dependent adjustments were made for ever use of pioglitazone; results were pooled using fixed and random effects meta-regression.

During a median follow-up of 4 to 7.4 years, there were 3,248 cases of incident bladder cancer, with 117 exposed cases.

No evidence was demonstrated for any association between cumulative exposure to pioglitazone and bladder cancer in men (RR per 100 days of cumulative exposure=1.01; 95% CI, 0.97-1.06) or women (RR=1.04; 95% CI, 0.97-1.11) with adjustments for age, calendar year, diabetes duration, smoking and any ever use of pioglitazone.

Further, no association seen between rosiglitazone and bladder cancer in men (RR=1.01; 95% CI, 0.98-1.03) or women (RR=1; 95% CI, 0.94-1.07).

“The decision to use any drug needs to weigh the risks and benefits associated with that drug,” Colhoun said. “We do not find evidence of bladder cancer being a concern with pioglitazone, but the decision to use the drug should be taken in the context of other known side effects, including fracture risk.”

Calhoun underscored that these data should provide reassurance for patients who have already used the drug and were worried by previous reports about bladder cancer.

The strengths of this particular research, according to investigators, were that “most observational pharmacoepidemiological studies are limited by allocation bias” and that they also “considered exposure to other glucose-lowering drugs in the models.”

Limitations to the study included short-term follow-up duration and absence of data on ethnicities other than white Europeans, BMI and smoking, the researchers conceded.

“Longer-term studies observational of real world exposure to diabetes drugs remain important, not just for this class of drugs, but other diabetes drugs too,” Colhoun said. “Such studies need to be careful to use methods that minimize biases.” – by Allegra Tiver