Document Detail


Association between longer therapy with thiazolidinediones and risk of bladder cancer: a cohort study.
MedLine Citation:
PMID:  22878886     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The use of pioglitazone, a thiazolidinedione (TZD), may increase the risk of bladder cancer in patients with type 2 diabetes. In this study, we assessed the risk of bladder cancer associated with the use of TZDs and between pioglitazone and rosiglitazone, an alternative TZD.
METHODS: We conducted a retrospective cohort study of patients with type 2 diabetes mellitus who initiated treatment with a TZD (n = 18 459 patients) or a sulfonylurea (SU) (n = 41 396 patients) between July 1, 2000, and August 31, 2010, using The Health Improvement Network database in the United Kingdom. Incident cancers were identified for 196 708 person-years of follow-up. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of bladder cancer in the TZD cohort compared with the SU cohort (referent), adjusted for potential confounders. Risk associated with increasing duration of drug exposure was also examined. All statistical tests were two-sided.
RESULTS: We identified 60 incident bladder cancers in the TZD cohort and 137 cancers in the SU cohort. No difference in bladder cancer risk was found between the two cohorts (TZD vs SU, HR = 0.93, 95% CI = 0.68 to 1.29) in analyses that did not account for duration of exposure. However, the risk of bladder cancer was increased among patients with the longest duration of TZD vs SU therapy (≥ 5 years of use, HR = 3.25, 95% CI = 1.08 to 9.71) and among those with the longest time since initiation of therapy (≥ 5 years since first use, HR = 2.53, 95% CI = 1.12 to 5.77). Risk of bladder cancer also increased with increasing time since initiation of pioglitazone (P (trend) < .001) and rosiglitazone (P (trend) = .006). Comparison of pioglitazone to rosiglitazone use did not demonstrate difference in cancer risk (P = .49).
CONCLUSION: Long-term TZD therapy (≥ 5 years) in patients with type 2 diabetes may be associated with an increased risk of bladder cancer, which may be common to all TZDs.
Authors:
Ronac Mamtani; Kevin Haynes; Warren B Bilker; David J Vaughn; Brian L Strom; Karen Glanz; James D Lewis
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-09
Journal Detail:
Title:  Journal of the National Cancer Institute     Volume:  104     ISSN:  1460-2105     ISO Abbreviation:  J. Natl. Cancer Inst.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-19     Completed Date:  2012-11-19     Revised Date:  2013-09-19    
Medline Journal Info:
Nlm Unique ID:  7503089     Medline TA:  J Natl Cancer Inst     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1411-21     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
Aged
Cohort Studies
Confounding Factors (Epidemiology)
Diabetes Mellitus, Type 2 / drug therapy*
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Great Britain / epidemiology
Humans
Hypoglycemic Agents / administration & dosage*,  adverse effects*
Male
Middle Aged
Proportional Hazards Models
Research Design
Retrospective Studies
Risk Assessment
Risk Factors
Thiazolidinediones / administration & dosage*,  adverse effects*
Urinary Bladder Neoplasms / chemically induced*,  epidemiology*
Grant Support
ID/Acronym/Agency:
K24 DK078228/DK/NIDDK NIH HHS; K24-DK078228/DK/NIDDK NIH HHS; T32-CA009679-20/CA/NCI NIH HHS; UL1-RR024134/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Hypoglycemic Agents; 0/Thiazolidinediones; 122320-73-4/rosiglitazone; X4OV71U42S/pioglitazone
Comments/Corrections

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