Pioglitazone use and risk of bladder cancer in patients with type 2 diabetes: retrospective cohort study using datasets from four European countries

Abstract

Objective To evaluate the association between pioglitazone use and bladder cancer risk in patients with type 2 diabetes.Design Retrospective cohort study using propensity score matched cohorts.Settings Healthcare databases from Finland, the Netherlands, Sweden, and the United Kingdom. Data comprised country specific datasets of linked records on prescriptions, hospitals, general practitioners, cancer, and deaths.Participants Patients with type 2 diabetes who initiated pioglitazone (n=56 337) matched with patients with type 2 diabetes in the same country exposed to diabetes drug treatments other than pioglitazone (n=317 109). Two matched cohorts were created, using a 1:1 fixed ratio (nearest match cohort) and a 1:10 variable ratio (multiple match cohort). Patients were matched on treatment history and propensity scores accounting for several variables associated with pioglitazone initiation.Main outcome measures Hazard ratios and 95% confidence intervals were estimated by Cox’s proportional hazards model with adjustments for relevant confounders. To assess the robustness of the findings, several sensitivity and stratified analyses were performed.Results In the cohort exposed to pioglitazone treatment, 130 bladder cancers occurred over a mean follow-up time of 2.9 years. In the nearest match and multiple match cohorts not exposed to pioglitazone treatment, 153 and 970 bladder cancers were recorded, with a mean follow‑up time of 2.8 and 2.9 years, respectively. With regards to bladder cancer risk, the adjusted hazard ratio for patients ever exposed versus never exposed to pioglitazone was 0.99 (95% confidence interval 0.75 to 1.30) and 1.00 (0.83 to 1.21) in the nearest and multiple match cohorts, respectively. Increasing duration of pioglitazone use and increasing cumulative dose were not associated with risk of bladder cancer (>48 months of pioglitazone use, adjusted hazard ratio 0.86 (0.44 to 1.66); >40 000 mg cumulative dose, 0.65 (0.33 to 1.26) in the nearest match cohort).Conclusions This study shows no evidence of an association between ever use of pioglitzone and risk of bladder cancer compared with never use, which is consistent with results from other recent studies that also included a long follow-up period.Trial registration Registered to the European Union electronic register of post-authorisation studies (EU PAS register no EUPAS3626).

Pioglitazone and risk of mortality in patients with type 2 diabetes: results from a European multidatabase cohort study

“…General strengths and weaknesses of the study have been reported previously 20. The cohort matching and regression modeling processes were designed for the primary outcome of incident bladder cancer.…”

“…Descriptive data and standardized differences comparing the pioglitazone-exposed and non-pioglitazone-exposed groups were presented in the primary manuscript 20. Crude all-cause and bladder cancer mortality rates were estimated with 95% CIs using Poisson regression.…”

A systematic review of observational studies of the association between pioglitazone use and bladder cancer

“…Out of the 20 included studies, 15 used a cohort approach [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. The study by Lewis et al [28] presents a re-analysis of data from a previous article [30].…”

Do We Still Need Pioglitazone for The Management of Type 2 Diabetes Mellitus? A Peep In To Risk of Bladder Cancer in Diabetic Population

“…01 and HR = 1.68; 95% CI 1.36-2.08; P < 0.00001; respectively) and duration (12-24 and >24 months) (HR = 1.43; 95% CI 1.19-1.71; P = 0.0001 and HR = 1.58;95% CI 1.27-1.97; P < 0.0001 respectively) of pioglitazone use is associated with risk of bladder cancer. On the contrary, a retrospective cohort study performed by Korhonen et al [14]. uses datasets from four European countries evaluating association between pioglitazone use and bladder cancer risk in T2DM patients.…”