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The Use of Long-Acting Insulin Analogs and the Risk of Colorectal Cancer Among Patients with Type 2 Diabetes: A Population-Based Cohort Study

Abstract

Introduction

The association between long-acting insulin analogs and colorectal cancer is uncertain, with previous studies reporting discrepant findings.

Objective

To determine whether the use of long-acting insulin analogs is associated with an increased risk of colorectal cancer, when compared with use of intermediate-acting human insulins among patients with type 2 diabetes.

Methods

We conducted a population-based study using the United Kingdom Clinical Practice Research Datalink (CPRD). We identified patients newly treated with either a long-acting insulin analog or an intermediate-acting human insulin between September 1, 2002 and January 31, 2018, with follow-up until January 31, 2019. Each long-acting insulin analog user was propensity score-matched to one intermediate-acting human insulin user, and a lag of 1 year was imposed. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of colorectal cancer, comparing long-acting insulin analogs with intermediate-acting human insulin. Secondary analysis was conducted to assess whether there was a duration–response relationship.

Results

A total of 10,734 new long-acting insulin analog users were matched to 10,734 new intermediate-acting human insulin users. After a median follow-up of 2.8 years, the use of long-acting insulin analogs was not associated with an increased risk of colorectal cancer, compared with intermediate-acting human insulin (1.80 vs. 1.87 per 1000 person-years, respectively; HR 0.96, 95% CI 0.70–1.34). There was no evidence of a duration–response relationship.

Conclusions

The results of this population-based study indicate that use of long-acting insulin analogs is not associated with an overall increased risk of colorectal cancer.

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Author information

All authors conceived and designed the study. Laurent Azoulay acquired the data. Richeek Pradhan, Hui Yin, and Laurent Azoulay did the statistical analyses. All authors analyzed and interpreted the data. Richeek Pradhan wrote the manuscript, and all authors critically revised the manuscript. Laurent Azoulay supervised the study and is the guarantor. All authors approved the final version of the manuscript and are accountable for its accuracy.

Correspondence to Laurent Azoulay.

Ethics declarations

Conflict of interest

Laurent Azoulay has received consulting fees from Janssen for work unrelated to this study. Richeek Pradhan, Hui Yin, and Oriana Yu have no relevant conflicts of interest to disclose.

Funding

This study was funded by the foundation scheme grant from the Canadian Institutes of Health Research (FDN-14328). Richeek Pradhan is the recipient of a training grant from the Canadian Institutes of Health Research Drug Safety and Effectiveness Training Program. Oriana Yu holds a Chercheur-Boursier Clinicien Junior 1 award from the Fonds de Recherche du Québec-Santé (FRQS). Laurent Azoulay holds a Chercheur-Boursier Senior award from the FRQS and is the recipient of a William Dawson Scholar award from McGill University.

Ethics approval

The study protocol was approved by the Independent Scientific Advisory Committee of the Clinical Practice Research Datalink (protocol No. 15_005R) and the Research Ethics Board of the Jewish General Hospital, Montreal, Canada.

Data sharing

Due to the data sharing policy of the Clinical Practice Research Datalink protecting patient privacy, it is not possible to share patient-level data.

Electronic supplementary material

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Pradhan, R., Yin, H., Yu, O.H.Y. et al. The Use of Long-Acting Insulin Analogs and the Risk of Colorectal Cancer Among Patients with Type 2 Diabetes: A Population-Based Cohort Study. Drug Saf 43, 103–110 (2020). https://doi.org/10.1007/s40264-019-00892-5

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