Cohort studyindependent cross-checkabstract checked★ key study I-ODD-123 in-depth review

US cohort of 193,099: no significant bladder cancer increase with pioglitazone

Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes.

Overview

Lewis JD et al.. JAMA 2015 · PMID 26197187 · DOI 10.1001/jama.2015.7996

Adjusted HR 1.06 (0.89-1.26).

Does the study support the specific claim? No · Methodological quality: high

Study explained simply

What did the researchers want to find out?: Test pioglitazone and cancer risk.
How was the study done?: Cohort and nested case-control.
How many people, animals or samples were studied?: 193,099 people.
What was actually found?: No significant bladder cancer increase.
How large was the observed effect?: HR 1.06.
What do the results mean in everyday life?: The bladder cancer risk, if any, is small.
What are the study's limitations?: Observational.
What does it say about Elawady's specific claim?: Contradicts a firm 63% increase.
Do the results apply to Germany and Europe?: High.
What can explicitly not be concluded from this study?: No risk at all.

Authors: Lewis JD et al.
Journal: JAMA
Year: 2015
Identifier: PMID 26197187 DOI 10.1001/jama.2015.7996
Verification: verified – PubMed efetch 2026-10-26; Crossref works API 2026-10-26
Retracted: no
Corrections: none
Extent checked: abstract only
Conflicts of interest and funding: Non-US government support listed in PubMed record; sponsor details not reviewed (abstract only).

Is pioglitazone associated with bladder cancer and 10 other cancers?

Study design: Cohort study – Cohort and nested case-control study (Kaiser Permanente Northern California)
Population: Persons with diabetes aged >=40
Country: USA
Period: 1997-2012
Sample size: 193,099 (bladder cohort); 464 cases and 464 controls; 236,507 (other cancers)
Inclusion and exclusion criteria: Members with diabetes

Exposure / intervention: Pioglitazone ever use, duration, cumulative dose (time-dependent)
Comparator: Non-use
Endpoints: Incident bladder cancer and 10 other cancers
Statistical methods: Cox models; conditional logistic regression with survey-based confounders

Results: Bladder cancer: crude incidence 89.8 vs 75.9 per 100,000 PY; adjusted HR 1.06 (0.89-1.26); case-control OR 1.18 (0.78-1.80). No clear pattern with duration or dose. Prostate cancer HR 1.13 (1.02-1.26) and pancreatic cancer HR 1.41 (1.16-1.71) increased.
Absolute risks: Crude 89.8 vs 75.9 per 100,000 person-years.
Authors' conclusion: Pioglitazone was not associated with a statistically significant increase in bladder cancer, although an increased risk could not be excluded.

CI log-symmetric (stats/C-ODD-12.py); upper limit 1.26 excludes the 63% increase claimed.

Large high-quality cohort that does not reproduce a 63% increase.

Tuccori 2016 (A-ODD-03), HR 1.63.

High.

Argues the 63% estimate is not consistent across populations.

Multidimensional assessment
Multidimensional assessment
Authenticity of the source	verified
Methodological quality	high
Risk of bias	some concerns
Precision of results	high
Directness	direct
Reproducibility	partly replicated
Consistency with the overall evidence	mixed
Regional transferability	high
Adequacy of the interpretation (by the archive)	not applicable

Long-term high-dose exposure.