Risk of Bladder Cancer among Patients with Diabetes Treated with a 15 mg Pioglitazone Dose in Korea: A Multi-Center Retrospective Cohort Study

Abstract

It has not yet been determined whether chronic exposure to relatively low doses of pioglitazone increases risk of bladder cancer. We aimed to assess the risk of bladder cancer associated with pioglitazone in Korean patients. This was a retrospective cohort study of diabetic patients who had ≥ 2 clinic visits between November 2005 and June 2011 at one of four tertiary referral hospitals in Korea. A prevalent case-control analysis nested within the cohort was conducted to further adjust confounders. A total of 101,953 control patients and 11,240 pioglitazone-treated patients were included, in which there were 237 and 30 cases of incidental bladder cancer (64.9 and 54.9 per 100,000 person-years; age, sex-adjusted HR 1.135, 95% confidence interval [CI] 0.769-1.677), respectively. In the prevalent case-control analysis nested within the cohort, use of pioglitazone for a duration of > 6 months, but not ever use of pioglitazone, was associated with an increased rate of bladder cancer as compared to never use of pioglitazone. In conclusion, we failed to exclude the possible association between use of pioglitazone for a duration of > 6 months and bladder cancer.Graphical Abstract

Ten‐year observational follow‐up of PROactive: a randomized cardiovascular outcomes trial evaluating pioglitazone in type 2 diabetes

“…In addition, some short-term, population-based cohorts in the USA [15], India [23], Japan [24], Korea [25], Taiwan [26,27] and the UK [28] also reported no association between pioglitazone and bladder cancer. In contrast, other short-term, observational database studies have suggested an association between exposure to pioglitazone and incidence of bladder cancer, including a retrospective cohort study using French National Health Insurance Plan data [29], and nested case-control studies in Taiwan [30], the UK [31] and Korea [32].…”

Pioglitazone and Sitagliptin: An Urgent Call for New Regulations Controlling all the Post Marketing Drug Safety Studies

“…Again, when I carefully read in a scientific paper that: "a pooled analysis of 25 randomized clinical trials does not indicate that treatment with sitagliptin increases cardiovascular risk in patients with type 2 diabetes mellitus. In a subanalysis, a higher rate of cardiovascular-related events was associated with sulphonylurea relative to sitagliptin" to discover at the end of the paper that "all studies and analyses described in this review were funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ" [4] or to read at the end of another similar paper that it was "supported by Merck Sharp & Dohme, a subsidiary of Merck" [5] this simply makes me feel uncomfortable or even suspicious and I don't believe that it's logic not to feel so especially when these results argue with other independent studies [6][7][8].…”

Pioglitazone and bladder cancer risk: a systematic review and meta‐analysis

“…The included studies were of adequate quality, with more than six stars out of nine in the NOS quality assessment (Table ). Five observational studies were sponsored by industry (Takeda) .…”