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Ca :

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Diabetologia DOI 10.1007/s00125-012-2534-0

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Patients with type 2 diabetes have a 40%increased risk of bladder cancer.

Diabetologia 2006; 49: 2819-23.

Diabetes Care 2010;33:1674-85.

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Cohort Study ofPioglitazone and Cancer

Incidence in 252,467 Patients With Diabetes aged >40

We found no clear evidence of an associationbetween use of pioglitazone and risk of the incidentcancers examined (prostate, female breast,

lung/bronchus, endometrial, colon, NHL, pancreas,kidney/renal pelvis, rectal, and melanoma).Because the maximum duration of follow-up wasfewer than 6 years after the initiation of

pioglitazone, longer-term studies are needed.

Diabetes Care 2011; 34:923929

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Use ofTZDs and the Risk ofColorectal Cancer in

Patients With Diabetes

A nationwide, population-based, case-control

study

The use of TZDs may be associated with a

decreased risk of colorectal cancer in patients

with diabetes. Further studies are warranted

to confirm our findings.

DOI: 10.2337/dc11-2197

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Safety and tolerability of pioglitazone in high-risk patients

with type 2 diabetes: an overview of data from PROactive.

The comparative incidence of malignancies was

similar; however, more cases of bladder

neoplasm (14 vs 5) and fewer cases of breast

cancer (3 vs 11) were observed in the

pioglitazone versus placebo arms of the study

Drug Saf 2009;32(3):187-202

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In 2011, the FDA issued a safety warning for

pioglitazone. The warning states that use for

longer than 1 year might be associated with

excess risk for bladder cancer, based on data

from a French study and an interim analysis of a

manufacturer-sponsored, U.S. observational

study.

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Risk of Bladder Cancer Among 193.099 Patients (30.173 Treated

With Pioglitazone). Interim report of a longitudinal cohort study

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Pioglitazone and risk of bladder cancer among diabetic

patients in France: a population-based cohort study

French national health insurance information

system linked with the French hospital discharge

database

Patients aged 40 to 79 years

Prescription for a glucose-lowering drug in 2006

Follow-up for 42 months

1.491.060 diabetic patients,

155.535 of whom were exposed to pioglitazone

Diabetologia 2012; 55:19531962

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Pioglitazone and risk of bladder cancer among diabetic

patients in France: a population-based cohort study

Diabetologia 2012; 55:19531962

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Pioglitazone and risk of bladder cancer among diabetic

patients in France: a population-based cohort study

Diabetologia 2012; 55:19531962

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Assessing the Association of Pioglitazone Use and

Bladder Cancer Through Drug Adverse Event Reporting

Diabetes Care 34:13691371, 2011

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Assessing the Association of Pioglitazone Use and

Bladder Cancer Through Drug Adverse Event Reporting

Diabetes Care 34:13691371, 2011

In agreement with preclinical and clinical studies, AERS

analysis is consistent with an association between

pioglitazone and bladder cancer. This issue needsconstant epidemiologic surveillance and urgent

definition by more specific studies.

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BMJ 2012 May 31; 344:e3645

The use of pioglitazone and the risk of bladder cancer in people

with type 2 diabetes: Nested case-control study (UK)

116,000 new users of oral antidiabetic drugs Mean follow-up of4.6years

470 patients had received diagnoses of bladder cancer (89

cases per 100,000 person-years)

Each patient with bladder cancer was matched with as manyas 20 controls

Ever use of pioglitazone was associated with 83% higher risk

for bladder cancer a significant increase compared

with never users The bladder cancer rate increased significantly with duration

of pioglitazone use, with the highest rates in patients who

were exposed for >2 years, and in patients whose

cumulative dose exceeded 28,000 mg.

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BMJ 2012 May 31; 344:e3645

The use of pioglitazone and the risk of bladder cancer in people

with type 2 diabetes: Nested case-control study(UK)

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BMJ 2012 May 31; 344:e3645

The use of pioglitazone and the risk of bladder cancer in people

with type 2 diabetes: Nested case-control study(UK)

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Pioglitazone and bladder cancer: a propensity

score matched cohort study

General Practice Research Database, UK(2001-

2010)

277014 patients (23548 on pio)

Adjusted HR for bladder Ca in the pio group for

the whole population = 1,16 (95% CI 0,83 1,62)

Adjusted HR for bladder Ca in the pio group for

patients with similar baseline characteristics =

1,22 (95% CI 0,88 1,84)

Br J Clin Pharmacol 2012; 75:254259

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Pioglitazone and bladder cancer: two

studies, same database, two answers

UK Clinical Practice Research Datalink (CPRD)

third generation pills and venous thromboembolism

proton pump inhibitors and fracture

oral bisphosphonates and gastrointestinal cancers

the same study population but a different study

design

Without a proper reanalysis or even a discussion

doi: 10.1111/bcp.12145

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The Risk of Bladder Cancer in KoreanDiabetic SubjectsTreated with Pioglitazone

Retrospective, matched case-control study

a case group (n=329) of diabetic patients with

bladder cancer

A control group of patients without bladder

cancer (1:2 ratio matching for sex and age,

n=658)

Diabetes Metab J 2012;36:371-378

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The Risk of Bladder Cancer in KoreanDiabetic SubjectsTreated with Pioglitazone

Diabetes Metab J 2012;36:371-378

6.4% vs. 15.0%, P

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Association between longer therapy with TZD s and

risk of bladder cancer: a retrospectivecohort study.

TZD (n = 18 459 patients) or SU (n = 41 396 patients)

2000 - 2010, using The Health Improvement Networkdatabase in the UK.

for 196 708 person-years of follow-up TZD vs SU, HR = 0.93 (95% CI = 0.68 - 1.29)

TZD vs SU therapy 5 years of use, HR = 3.25, (95% CI= 1.08 - 9.71)

Comparison of pioglitazone to rosiglitazone use did notdemonstrate difference in cancer risk (P = .49).

J Natl Cancer Inst 2012;104(18):1411-21.

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Pioglitazone and Bladder Cancer

A population-based study ofTaiwanese

1,000,000 individuals were randomly sampled fromthe National Health Insurance database

54,928 patients with type 2 diabetes and without

previous bladder cancer

incident cases of bladder cancer 2006 to 2009

165 incident case subjects

(0.39%) ever users vs (0.30%) never users ofpioglitazone (adjusted HR 1.305 [95% CI 0.6612.576]).

Diabetes Care 35:278280, 2012

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Use ofTZDsand the risk of bladder canceramong people with type 2 diabetes: a meta-analysis

through March 2012

published andunpublished studies (1787)

without language restrictions

Included 4 RCTs (PROactive, ADOPT, RECORD, Sanofi), 5

cohort studies (California, 2 Taiwan, France)

and 1casecontrol studies

CMAJ 2012; 184: E675-E683

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Use ofTZDs and the risk of bladder cancer

among people with type 2 diabetes: a meta-analysis

CMAJ 2012; 184: E675-E683

Meta-analysis of the risk of bladder cancer associated with pioglitazone use among

adults with type 2 diabetes in cohort studies.

RCTs evaluated rosiglitazone use

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Use ofTZDs and the risk of bladder cancer

among people with type 2 diabetes: a meta-analysis

The limited evidence available supports the

hypothesis that thiazolidinediones, particularly

pioglitazone, are associated with an increased

risk of bladder cancer among adults with type 2

diabetes.

CMAJ 2012; 184: E675-E683

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Cancer risk for patients using TZDs for type 2

diabetes: a meta-analysis (Italy)

studies published in English up to June 30, 2012

3 case-control studies and 14 cohort studies

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).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 relationswere 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)

Oncologist 2013;18:148-56.

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Pioglitazone and risk of bladder cancer: a

meta-analysis ofcontrolledstudies

Six studies involving 215 142 patients using

pioglitazone were included,

a median period of follow-up of 44 months.

Diabetic Medicine 2013. doi: 10.1111/dme.12144

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Pioglitazone and risk of bladder cancer: a

meta-analysis ofcontrolledstudies

the number needed to harm was 5 additional

cases of bladder cancer per 100 000 personyears.

Diabetic Medicine 2013. doi: 10.1111/dme.12144

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