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Acta Diabetologica

, Volume 51, Issue 1, pp 91–101 | Cite as

Thiazolidinediones and cancer: results of a meta-analysis of randomized clinical trials

  • Matteo MonamiEmail author
  • Ilaria Dicembrini
  • Edoardo Mannucci
Original Article

Abstract

Recent epidemiological data have contributed to the formulation of the hypothesis about the long-term safety of pioglitazone, a thiazolidinedione (TZD), with respect to malignancies, in particular bladder cancer. The primary aim of this meta-analysis of randomized clinical trials, not designed a priori to test this hypothesis, was to explore whether TZDs affect the risk of cancer. A meta-analysis was performed including published and unpublished randomized trials with a duration of at least 52 weeks, enrolling patients with or without diabetes, comparing TZDs with either placebo or other drug therapies on various different outcomes. We found 22 trials reporting at least one cancer and enrolling 13,197 patients to TZD (pioglitazone: n = 3,710 and rosiglitazone: n = 9,487) and 12,359 to placebo or active comparator groups. The mean follow-up was 26.1 months. Overall, those assigned at random to TZDs had a significant reduction (MH-OR 0.85 [0.73–0.98]; p = 0.027) in the incidence of malignancies, with no significant difference in effect between pioglitazone and rosiglitazone. Specifically, subgroup analyses showed a significant reduction for rosiglitazone (MH-OR 0.82 [0.69–0.98]; p = 0.029), but not for pioglitazone (MH-OR 0.66 [0.34–1.28]; p = 0.22). In further subgroup analyses of site-specific malignancies based on the data from four trials, the risk of bladder cancer with pioglitazone (MH-OR) was 2.05 [0.84–5.02]; p = 0.12. Further, rosiglitazone, but not pioglitazone, was associated with a significantly reduced risk of bowel cancer. In contrast, pioglitazone, but not rosiglitazone, was associated with a significant reduction in breast cancer. The present meta-analysis of trials, not designed a priori to test the hypothesis, provides reassuring evidence that TZDs are not associated with risk of overall malignancies. In fact, they are compatible with the possibility of a decreased risk of cancer. In site-specific subgroup analyses, for rosiglitazone, there was a significant decreased risk of bowel cancer. Subgroup analyses for pioglitazone did not allow to exclude an increased risk of bladder cancer, while the risk of breast cancer was significantly decreased. While these data are also useful to formulate not test hypotheses, they provide somewhat more cogent evidence than the previously published epidemiological data.

Keywords

Thiazolidinediones Cancer Type 2 diabetes 

Notes

Conflict of interest

Matteo Monami has received speaking fees from Bristol Myers Squibb, Merck, Novartis, Novo Nordisk, and Takeda. Ilaria Dicembrini has received speaking fees from Novo Nordisk. Edoardo Mannucci has received consultancy fees from Merck and Novartis, speaking fees from Astra Zeneca, Bristol Myers Squibb, Merck, and Novartis, and research grants from Merck, Novartis, and Takeda.

Supplementary material

592_2013_504_MOESM1_ESM.rtf (99 kb)
Supplementary material 1 (RTF 98 kb)

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Copyright information

© Springer-Verlag Italia 2013

Authors and Affiliations

  • Matteo Monami
    • 1
    Email author
  • Ilaria Dicembrini
    • 2
  • Edoardo Mannucci
    • 3
  1. 1.Geriatric CardiologyCareggi Teaching HospitalFlorenceItaly
  2. 2.Obesity AgencyCareggi Teaching HospitalFlorenceItaly
  3. 3.Diabetes Agency, Careggi Teaching HospitalAzienda Ospedaliero-Universitaria CareggiFlorenceItaly

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