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Dipeptidyl Peptidase-4 Inhibitors and the Risk of Gallbladder and Bile Duct Disease Among Patients with Type 2 Diabetes: A Population-Based Cohort Study

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Abstract

Introduction

The use of dipeptidyl peptidase-4 (DPP-4) inhibitors may be associated with an increased risk of gallbladder and bile duct disease among patients with type 2 diabetes.

Methods

We conducted a population-based cohort study using an active comparator, new-user design. We used data from the United Kingdom Clinical Practice Research Datalink to identify patients newly treated with either a DPP-4 inhibitor or sodium-glucose cotransporter-2 (SGLT-2) inhibitor between January 2013 and December 2020. We fitted Cox proportional hazards models with propensity score fine stratification weighting to estimate the hazard ratio (HR) and its 95% confidence interval (CI) for incident gallbladder and bile duct disease associated with DPP-4 inhibitors compared to SGLT-2 inhibitors.

Results

DPP-4 inhibitors were associated with a 46% increased risk of gallbladder and bile duct disease (4.3 vs. 3.0 events per 1000 person-years, HR 1.46, 95% CI 1.17–1.83). At 6 months and 1 year, 745 and 948 patients, respectively, would need to be treated with DPP-4 inhibitors for one patient to experience a gallbladder or bile duct disease.

Conclusions

In this population-based cohort study, the use of DPP-4 inhibitors, when compared with SGLT-2 inhibitors, was associated with a moderately increased risk of gallbladder and bile duct disease among patients with type 2 diabetes. This outcome was still quite rare with a high number needed to harm at 6 months and 1 year.

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Authors and Affiliations

  1. Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine, H425.1, Montreal, H3T 1E2, Canada

    Samantha B. Shapiro, Hui Yin & Laurent Azoulay

  2. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, H3A 1G1, Canada

    Samantha B. Shapiro & Laurent Azoulay

  3. Division of Endocrinology, Jewish General Hospital, Montreal, H3T 1E2, Canada

    Oriana H. Y. Yu

  4. Gerald Bronfman Department of Oncology, McGill University, Montreal, H4A 3T2, Canada

    Laurent Azoulay

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  1. Samantha B. Shapiro
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  2. Hui Yin
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  3. Oriana H. Y. Yu
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  4. Laurent Azoulay
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Corresponding author

Correspondence to Laurent Azoulay.

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Funding

This research was funded by a Foundation Scheme grant from the Canadian Institutes of Health Research (FDN-143328). SBS is the recipient of a doctoral training award from the Canadian Institutes of Health Research. LA is the recipient of a Distinguished Research Scholar Award from the Fonds de recherche du Québec—Santé and received a William Dawson Scholar award from McGill University. The study funder was not involved in the design of the study; the collection, analysis, and interpretation of data; and writing the report; and did not impose any restrictions regarding the publication of the report.

Conflict of Interests

This study was funded by the Canadian Institutes of Health Research. LA has received speaking and consulting fees from Pfizer and Roche for work unrelated to this project. OY was involved in an advisory board meeting for Novo Nordisk for work unrelated to this study. All other authors declare no conflicts of interest. LA is an Editorial Board member of Drug Safety. LA was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.

Ethics Approval

The study protocol was approved by the Research Data Governance of the CPRD (protocol 23_002543) and by the Research Ethics Board of the Jewish General Hospital, Montreal, Canada.

Data Availability

No data are available. This study is based on data from the CPRD obtained under license from the UK Medicines and Healthcare products Regulatory Agency. The data are provided by patients and collected by the UK National Health Service as part of their care and support. The interpretation and conclusions contained in this study are those of the authors alone. Because electronic health records are classified as “sensitive data” by the UK Data Protection Act, information governance restrictions (to protect patient confidentiality) prevent data sharing via public deposition. Data are available with approval through the individual constituent entities controlling access to the data. Specifically, the primary care data can be requested via application to the CPRD (https://www.cprd.com).

Code Availability

Codes may be made privately available upon reasonable request to the corresponding author.

Consent to Participate

Not applicable.

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Not applicable.

Author Contributions

SBS wrote the manuscript, and all authors edited, critically reviewed, and approved the final version of the manuscript. All authors conceived and designed the study, analyzed and interpreted the data, approved the final version of the manuscript, and are accountable for its accuracy. SBS, HY, and LA performed the statistical analyses. LA acquired the data and supervised the study.

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Shapiro, S.B., Yin, H., Yu, O.H.Y. et al. Dipeptidyl Peptidase-4 Inhibitors and the Risk of Gallbladder and Bile Duct Disease Among Patients with Type 2 Diabetes: A Population-Based Cohort Study. Drug Saf (2024). https://doi.org/10.1007/s40264-024-01434-4

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