Pioglitazone prescription increases risk of bladder cancer in patients with type 2 diabetes: an updated meta-analysis
- First Online:
- 700 Downloads
Pioglitazone is widely used for glycemic control in patients with type 2 diabetes mellitus, but evidence regarding the association between pioglitazone and bladder cancer risk is confusing. A systematic search of databases was carried out, and other relevant papers were also identified. Then, the analyses were conducted according to the PRISMA and MOOSE guidelines. After quality assessment, nine datasets from 10 available studies were included on the basis of inclusion criteria. The incidence of bladder cancer among pioglitazone ever users and never users, pooled from four cohort and one randomized studies, were 84.51 and 66.68 per 100,000 person-years, respectively. Nine studies representing 2,596,856 diabetic patients were recognized as eligible for overall study; the result suggested an increased risk of bladder cancer in patients exposed to pioglitazone. A persistent significance was detected after being adjusted by age, gender, and use of other diabetes medications. Subgroup analyses indicated that the significantly increased incidence of bladder cancer was found in men, but not in women. Additionally, the analyses addressing increasing exposure to pioglitazone observed a dose–response relation between exclusive ever use of pioglitazone and bladder cancer in terms of cumulative duration of use and cumulative dosage. With some limitations, our results suggest an increased risk of bladder cancer in diabetic patients using pioglitazone, especially for men with long-term and high-dose exposure. Additional studies are needed to provide more precise evidences to support our results.
KeywordsPioglitazone Bladder cancer Diabetes Meta-analysis
- 3.Food and Drug Administration. FDA drug safety communication: ongoing safety review of Actos (pioglitazone) and potential increased risk of bladder cancer after two years exposure. http://www.fda.gov/Drugs/DrugSafety/ucm226214.htm (accessed Oct 1, 2010)
- 5.Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366:1279–89.PubMedCrossRefGoogle Scholar
- 14.Questions and answers on the review of pioglitazone-containing medicines (Actos, Glustin, Competact, Glubrava and Tandemact). European Medicines Agency. 2011. www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/2011/07/WC500109179.pdf. Accessed Oct 2012.
- 18.Phillips B, Ball C, Sackett D, et al. Levels of evidence and grades of recommendation. Oxford Centre for Evidence-based Medicine Web site. http://www.cebm.net/index.aspx?o=1025. Accessed Oct 2012.
- 25.Jain S, Pulikuri S, Zhu Y, Qi C, Kanwar YS, Yeldandi AV, et al. Differential expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) and its coactivators steroid receptor coactivator-1 and PPAR-binding protein PBP in the brown fat, urinary bladder, colon, and breast of the mouse. Am J Pathol. 1998;153:349–54.PubMedCentralPubMedCrossRefGoogle Scholar