title: Pioglitazone has a dubious bladder cancer risk but an undoubted cardiovascular benefit.
abstract: On 8 April 2014, a US jury ordered Takeda and Eli Lilly to pay $9 bn in punitive damages after finding that they had concealed the cancer risks associated with pioglitazone. By contrast, on 28 August 2014, the long-awaited outcome of the 10-year Kaiser Permanente Northern California study was announced. That study was specifically designed to investigate whether patients exposed to pioglitazone were at an increased risk of bladder cancer and found no association; thus, at last, the controversial issue has been resolved. A review, in retrospect, of the story of the proposed link between pioglitazone and bladder cancer reveals flaws at every stage. In 2012, a BMJ editorial, in keeping with some other contemporary reports, stated 'it can confidently be assumed that pioglitazone increases the risk of bladder cancer'. Examination of the information which led to such a statement shows that: 1) the pre-clinical findings of bladder cancer in male rats is not indicative of human risk; 2) there is no association between bladder cancer and pioglitazone in randomized controlled trials, once cases that could not plausibly be related to treatment are removed; and 3) the observational studies that have suggested a link have over-extrapolated from the data: pioglitazone-treated patients had more risk factors for bladder cancer than those not treated with pioglitazone. Meanwhile careful study of randomized controlled trials shows evidence of cardiovascular benefit from pioglitazone in Type 2 diabetes, a condition which results, more than anything, in premature cardiovascular death and morbidity.
authors.affiliation: Department of Diabetes and Endocrinology, City Hospital, Birmingham, UK.
authors.forename: R E J
authors.initials: RE
authors.lastname: Ryder
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004195:Disease Models, Animal; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D000077205:Pioglitazone; D051381:Rats; D012189:Retrospective Studies; D012307:Risk Factors; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology*
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone