A comparison of all-cause mortality with pioglitazone and insulin in type 2 diabetes: an expanded analysis from a retrospective cohort study

Abstract

Objectives:

The objectives of this study were to assess and compare all-cause mortality rates between pioglitazone (PIO) and insulin (INS).

Research design:

The study population included 56,536 patients with type 2 diabetes aged ≥45 years who were first-time users of PIO or INS. Data from 1 May 2000 until 30 June 2010 from the i3 InVision Data Mart database were linked to death records of the US Social Security Administration obtained in March 2012, with approval from the Institutional Review Board and in full compliance with the Health Insurance Portability and Accountability Act of 1996.

Main outcome measures:

Kaplan–Meier curves were generated and hazard ratios (HRs) were estimated for the occurrence of deaths in the PIO and INS cohorts using Cox proportional hazards models adjusted with inverse probability weights derived from propensity scores.

Results:

After adjustment for >40 covariates through inverse probability weights derived from propensity scores, the PIO group showed a significantly lower risk of all-cause mortality (HR 0.33; 95% confidence interval, 0.31, 0.36). The risk of all-cause mortality was also significantly lower in the PIO cohort than the INS cohort among subgroups based on baseline variables such as sex, age (<55 years, ≥55 years), antidiabetic medication use (sulfonylureas or metformin), lipid-altering medication use, and congestive heart failure status. The study has some limitations. Use of a claims database means a potential bias toward a younger cohort. Disease-specific mortality was not identified because of no recorded cause of death. Reliable information regarding the differences in disease deterioration rate and some clinical and lab results were not available, which limits the statistical adjustment of baseline variables.

Conclusion:

PIO was associated with a lower risk of all-cause mortality than INS.

Keywords::

• All-cause mortality
• Insulin
• Pioglitazone
• Type 2 diabetes mellitus

Transparency

Declaration of funding

This study was funded and conducted by Takeda Pharmaceuticals International Inc. and Takeda Development Center Americas Inc. The sponsors were involved in the design of the study, data collection, analysis and interpretation, the development of this manuscript, and the decision to submit the manuscript for publication.

Declaration of financial/other relationships

J.Y., C.V., M.B., A.P., H.L., G.J., and S.Y. have disclosed that they were employed by Takeda while performing and documenting this study.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgments

The authors acknowledge Sarah Baldock, Mary Gabb, and Pin Lu (Rx Communications, Mold, UK) for providing medical writing assistance in the development of the manuscript (funded by Takeda Pharmaceuticals International Inc). The authors also acknowledge Venkatesh Harikrishnan, an on-site contractor from Ranstad Pharma (Deerfield, IL, USA), for SAS programming support during the study.