Cancer risk for patients using thiazolidinediones for type 2 diabetes: a meta-analysis.
OBJECTIVE
To clarify and quantify the effect of thiazolidinediones (TZDs; e.g., pioglitazone, rosiglitazone) on the risk of bladder cancer, other selected cancers, and overall cancer in patients with type 2 diabetes, we performed a systematic review and meta-analysis of observational studies.


METHODS
A PubMed/MEDLINE search was conducted for studies published in English up to June 30, 2012. Random-effect models were fitted to estimate summary relative risks (RR).


RESULTS
Seventeen studies satisfying inclusion criteria (3 case-control studies and 14 cohort studies) were considered. Use of TZDs was not associated to the risk of cancer overall (summary RR: 0.96; 95% confidence interval [CI]: 0.91-1.01). A modest excess risk of bladder cancer was reported in pioglitazone (RR: 1.20; 95% CI: 1.07-1.34 from six studies) but not in rosiglitazone (RR: 1.08; 95% CI: 0.95-1.23 from three studies) users. The RRs of bladder cancer were higher for longer duration (RR: 1.42 for >2 years) and higher cumulative dose of pioglitazone (RR: 1.64 for >28,000 mg). Inverse relations were observed with colorectal cancer (RR: 0.93; 95% CI: 0.90-0.97 from six cohort studies) and liver cancer (RR: 0.65; 95% CI: 0.48-0.89 from four studies), whereas there was no association with pancreatic, lung, breast, and prostate cancers.


CONCLUSIONS
Adequate evidence excludes an overall excess cancer risk in TZD users within a few years after starting treatment. However, there is a modest excess risk of bladder cancer, particularly with reference to pioglitazone. Assuming that this association is real, the potential implications on the risk-benefit analysis of TZD use should be evaluated.
Department of Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa, 19 20156 Milano, Italy.
Cristina
C
Bosetti
Valentina
V
Rosato
Danilo
D
Buniato
Antonella
A
Zambon
Carlo
C
La Vecchia
Giovanni
G
Corrao
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced* / Q000188:drug therapy; D012307:Risk Factors; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use
D045162:Thiazolidinediones