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Meta-Analysis
. 2013;18(2):148-56.
doi: 10.1634/theoncologist.2012-0302. Epub 2013 Jan 23.

Cancer risk for patients using thiazolidinediones for type 2 diabetes: a meta-analysis

Cristina Bosetti  1 , Valentina Rosato, Danilo Buniato, Antonella Zambon, Carlo La Vecchia, Giovanni Corrao
Affiliations
Meta-Analysis

Cancer risk for patients using thiazolidinediones for type 2 diabetes: a meta-analysis

Cristina Bosetti et al. Oncologist. 2013.

Abstract

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.

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Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

Figures

Figure 1.
Figure 1.
Study-specific and summary relative risk estimates for use of thiazolidinediones (vs. no use of TZDs) and overall cancer risk. Abbreviations: CI, confidence interval; NHL, non-Hodgkin lymphoma; RR, relative risk; TZD, thiazolidinedione.
Figure 2.
Figure 2.
Study-specific and summary relative risk estimates for use of thiazolidinediones (vs. no use) and risk of selected cancer sites. Abbreviations: CI, confidence interval; RR, relative risk; TZD, thiazolidinedione.
Figure 3.
Figure 3.
Study-specific and summary relative risk estimates for thiazolidinediones (use vs. no use and dose-response analyses) and risk of bladder cancer. Abbreviations: CI, confidence interval; RR, relative risk; TZD, thiazolidinedione.
Figure 4.
Figure 4.
Funnel plot for the studies on thiazolidinediones and cancer risk. Abbreviation: RR, relative risk.
See this image and copyright information in PMC

Comment in

  • Thiazolodinediones and cancer: duplicate publication bias?
    de Vries F, Zeegers MP, Knapen LM, Goossens ME. de Vries F, et al. Oncologist. 2013;18(10):1147. doi: 10.1634/theoncologist.2013-0087. Oncologist. 2013. PMID: 24149711 Free PMC article.
  • In reply.
    Bosetti C, Rosato V, Buniato D, Zambon A, La Vecchia C, Corrao G. Bosetti C, et al. Oncologist. 2013;18(10):1148. doi: 10.1634/theoncologist.2013-0216. Oncologist. 2013. PMID: 24149712 Free PMC article.

References

    1. Danaei G, Finucane MM, Lu Y, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: Systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet. 2011;378:31–40. - PubMed
    1. Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: A consensus report. Diabetes Care. 2010;33:1674–1685. - PMC - PubMed
    1. Renehan A, Smith U, Kirkman MS. Linking diabetes and cancer: A consensus on complexity. Lancet. 2010;375:2201–2202. - PubMed
    1. Bosetti C, Rosato V, Polesel J, et al. Diabetes Mellitus and cancer risk in a network of case-control studies. Nutr Cancer. 2012;64:643–651. - PubMed
    1. La Vecchia C. Diabetes mellitus, medications for type 2 diabetes mellitus, and cancer risk. Metabolism. 2011;60:1357–1358. - PubMed

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