Comparative safety of pioglitazone versus clinically meaningful treatment alternatives concerning the risk of bladder cancer in older US adults with type 2 diabetes
Open accessAbstract
Aims: To compare bladder cancer incidence between patients initiating pioglitazone treatment and patients initiating treatment with dipeptidyl‐peptidase‐4 inhibitors [DPP‐4s] or sulfonylureas. Methods: We identified M edicare beneficiaries aged >65 years who initiated treatment with pioglitazone ( N = 38 700), DPP‐4s ( N = 82 552) or sulfonylureas ( N = 126 104) between 2007 and 2014 after at least 6 months without prescriptions for these drug classes. Patients were followed from second prescription until bladder cancer outcome (2 claims within 60 days) using a 6‐month induction/latency period, censoring for treatment change, death or end of 2014. We used propensity score‐weighted C ox proportional‐hazards models to obtain adjusted hazard ratios (a HR ) and their 95% confidence intervals. Results: Overall mean age of participants was 75 years and 41% were men. Over a median of 1.2 treatment years, 727 beneficiaries developed bladder cancer. Pioglitazone initiators had an increased incidence of bladder cancer (308 vs 204 [DPP‐4s] or 231 [sulfonylureas] per 100 000 person‐years; aHR, 1.57 [1.23‐2.00] vs DPP‐4s and 1.32 [1.02‐1.70] vs sulfonylureas). The increased risk emerged within the first 2 years of treatment (aHR, 1.63 [1.22‐2.17] vs DPP‐4s and 1.32 [0.98‐1.78] vs sulfonylureas). If treatment was discontinued within the first 2 years, the risk after 2 years post initiation was attenuated (aHR, 0.89 [0.61‐1.28]) compared with patients treated for more than 2 years (aHR, 1.45 [0.93‐2.26]) both vs DPP‐4s. Findings were consistent across secondary and sensitivity analyses. Conclusions: Pioglitazone was associated with an elevated risk of bladder cancer compared with DPP‐4s and sulfonylureas. The elevated risk emerged within the first 2 years of treatment and was attenuated after discontinuing. Pioglitazone's relative effectiveness should be weighed against a small absolute increase in risk of bladder cancer.
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A decreased risk of colorectal adenomas and colorectal carcinoma is a consistent finding with metformin, with potential survival benefit for colorectal carcinoma.
“A decreased risk of colorectal adenomas and colorectal carcinoma is a consistent finding with a potential for a survival benefit for colorectal carcinoma.1784–1790”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [1786]
The Discussion addresses bladder-cancer risk associated with pioglitazone, and the Methods mention metformin only in relation to cohort selection. Searches for colorectal adenomas, colorectal cancer, and survival benefit found no passage addressing the claim. Page numbers were unavailable in our copy. (LLM, conf=0.78)
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- Authors
- Garry, E. M., Buse, J. B., Lund, J. L., Pate, V., & Stürmer, T.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Department of Epidemiology University of North Carolina at Chapel Hill Chapel Hill North Carolina
- Corresponding author
- Garry, Elizabeth M.
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2017-08-08
- Volume
- 20
- Issue
- 1
- Pages
- 129-140
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- PMC
- PMC7037672
- OpenAlex
- W2728654432
- Cited by
- 25
- References
- 35
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 5 · 2018: 5 · 2017: 2
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Pharmacoepidemiology Gillings Innovation Lab (PEGIL) (200811.0010)
- Center for Pharmacoepidemiology, Department of Epidemiology
- University ofNorth Carolina (UNC) Gillings School of Global Public Health
- CER Strategic Initiative of UNC's Clinical and Translational Science Award (UL1TR001111)
- Cecil G. Sheps Center for Health Services
- UNC School of Medicine
- National Institute on Aging (RO1 AG023178)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Surgery › Bladder and Urothelial Cancer Treatments
- Keywords
- pioglitazone, bladder cancer, type 2 diabetes, older adults, DPP-4 inhibitors, sulfonylureas, drug safety, cancer risk, treatment discontinuation, thiazolidinediones, antidiabetic drugs, Medicare beneficiaries, propensity score matching, hazard ratio, drug-induced cancer risk, drug repurposing
- MeSH terms
- Pioglitazone, Aged, Aged, 80 and over, Aging, Urinary Bladder Neoplasms, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Medicare, Humans, Hypoglycemic Agents, Male, Drug Prescriptions, Risk, Sulfonylurea Compounds, United States, Cohort Studies, Incidence, Proportional Hazards Models, Thiazolidinediones, Dipeptidyl-Peptidase IV Inhibitors, Electronic Health Records, Pharmacovigilance
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