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Abstract
Objectives Estimate and compare the risk of mortality in patients whose antidiabetic therapy is modified to include pioglitazone compared with an alternative antidiabetic medication at the same stage of disease progression.
Design Retrospective cohort study.
Setting Pooled analysis of clinical data collected from primary and/or secondary care settings in four European countries: Finland, The Netherlands, Sweden and the UK .
Participants 56 337 patients with type 2 diabetes mellitus first prescribed pioglitazone between 2000 and 2011, and 56 337 patients never prescribed pioglitazone matched by treatment stage, history of diabetes, diabetes complications and cardiovascular disease, and year of cohort entry using exact and propensity score matching. Patients were followed-up for a mean of 2.90 (SD 2.21) and 2.83 (SD 2.37) years in the pioglitazone-exposed and non-pioglitazone-exposed groups, respectively.
Outcomes All-cause mortality ascertained from clinical or registry data. Mortality was a planned secondary outcome in a study primarily studying the association of pioglitazone use with bladder cancer risk.
Results The crude overall mortality rate per 10 000 patient years was 206 (95% CI 199 to 213) in the pioglitazone-exposed group and 448 (95% CI 438 to 458) in the non-pioglitazone-exposed group. The crude HR comparing pioglitazone to alternative antidiabetic exposure was 0.46 (95% CI 0.45 to 0.48). This reduced in magnitude to 0.67 (95% CI 0.64 to 0.70) following further adjustment for matching variables, propensity scores, age, gender and time-dependent variables representing use of alternative antidiabetic drugs.
Conclusions In this large observational cohort study of patients with type 2 diabetes, pioglitazone exposure was associated with a statistically significant decrease in the risk of all-cause mortality across four European countries. Results should be interpreted with caution due to the potential for residual confounding.
Protocol registration European Network of Centres for Pharmacoepidemiology and Pharmacovigilance.
- Mortality
- Type 2 Diabetes
- Pioglitazone
- Electronic Medical Records
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Footnotes
Contributors All authors planned and designed the study. SC, MM, ML, EMH, LK-H, RW and HS performed the data management and data analysis, and all authors interpreted the data. All authors drafted the manuscript, revised the paper critically for important intellectual content and approved the final version of the manuscript. PK supervised the study and is the guarantor.
Competing interests All authors have completed the Unified CompetingInterest form at (available on request from the corresponding author) and declare that PK, FH,SC, and MM are employed by EPID Research, EH is and LKH was employed by PHARMOInstitute, RW and HS are employed by CPRD, and ML and SB are employed byKarolinska Institute. EPID Research, PHARMO Institute, CPRD and KarolinskaInstitute perform commissioned pharmacoepidemiological studies and thus theiremployees have been and currently are working in collaboration with severalpharmaceutical companies (including Takeda). PD is employed by Takeda
Patient consent This is a register-based study with anonymous data and no patient contact.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Criteria and process for sharing the analytical country-specific datasets and meta-analysis dataset for third parties is defined in the study protocol available at the ENCePP E-Register of Studies.