Global and Regional Effects of Bladder Cancer Risk Associated with Pioglitazone Therapy in Patients with Diabetes

It has been debated for several years as to whether the antidiabetic drug pioglitazone increases the risk for bladder cancer. A series of recent large population studies yielded conflicting results. To investigate why the observational studies yielded conflicting results, we conducted stratified analyses to analyze the potential confounders behind these discordant outcomes. A total of 2,764,731 participants from observational (OB) studies and 9,999 from randomized control trials (RCTs) were identified for these analyses. The stratified analysis revealed that the study type, adjustment for age/sex, treatment duration, cumulative dose, agents used in a control group, mean period of follow-up and study population region might contribute to the discordant outcomes. In terms of population regions, pioglitazone increased the risk for bladder cancer could be found in European population, and patients who undergo treatment with pioglitazone for longer durations (>12 months) or are administrated a larger cumulative dose (>28,000 mg) might require more attention, and the long-term effects (≥3.6 years) of pioglitazone needs be monitored more carefully.