Association between longer therapy with thiazolidinediones and risk of bladder cancer

A cohort study

Ronac Mamtani, Kevin Haynes, Warren B. Bilker, David J. Vaughn, Brian Strom, Karen Glanz, James D. Lewis

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

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.MethodsWe 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.ResultsWe 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 (Ptrend <. 001) and rosiglitazone (Ptrend =. 006). Comparison of pioglitazone to rosiglitazone use did not demonstrate difference in cancer risk (P =. 49).ConclusionLong-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.

Original languageEnglish (US)
Pages (from-to)1411-1421
Number of pages11
JournalJournal of the National Cancer Institute
Volume104
Issue number18
DOIs
StatePublished - Sep 19 2012

Fingerprint

Thiazolidinediones
pioglitazone
Urinary Bladder Neoplasms
Cohort Studies
rosiglitazone
Confidence Intervals
Type 2 Diabetes Mellitus
Therapeutics
Neoplasms
2,4-thiazolidinedione
Proportional Hazards Models
Retrospective Studies
Databases

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Mamtani, Ronac ; Haynes, Kevin ; Bilker, Warren B. ; Vaughn, David J. ; Strom, Brian ; Glanz, Karen ; Lewis, James D. / Association between longer therapy with thiazolidinediones and risk of bladder cancer : A cohort study. In: Journal of the National Cancer Institute. 2012 ; Vol. 104, No. 18. pp. 1411-1421.
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abstract = "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.MethodsWe 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.ResultsWe 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 (Ptrend <. 001) and rosiglitazone (Ptrend =. 006). Comparison of pioglitazone to rosiglitazone use did not demonstrate difference in cancer risk (P =. 49).ConclusionLong-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.",
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Association between longer therapy with thiazolidinediones and risk of bladder cancer : A cohort study. / Mamtani, Ronac; Haynes, Kevin; Bilker, Warren B.; Vaughn, David J.; Strom, Brian; Glanz, Karen; Lewis, James D.

In: Journal of the National Cancer Institute, Vol. 104, No. 18, 19.09.2012, p. 1411-1421.

Research output: Contribution to journalArticle

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T1 - Association between longer therapy with thiazolidinediones and risk of bladder cancer

T2 - A cohort study

AU - Mamtani, Ronac

AU - Haynes, Kevin

AU - Bilker, Warren B.

AU - Vaughn, David J.

AU - Strom, Brian

AU - Glanz, Karen

AU - Lewis, James D.

PY - 2012/9/19

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N2 - 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.MethodsWe 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.ResultsWe 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 (Ptrend <. 001) and rosiglitazone (Ptrend =. 006). Comparison of pioglitazone to rosiglitazone use did not demonstrate difference in cancer risk (P =. 49).ConclusionLong-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.

AB - 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.MethodsWe 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.ResultsWe 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 (Ptrend <. 001) and rosiglitazone (Ptrend =. 006). Comparison of pioglitazone to rosiglitazone use did not demonstrate difference in cancer risk (P =. 49).ConclusionLong-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.

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