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Dipeptidyl peptidase-4 inhibitors may accelerate cirrhosis decompensation in patients with diabetes and liver cirrhosis: a nationwide population-based cohort study in Taiwan

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Abstract

Background/purpose

Management of type 2 diabetes mellitus (T2DM) in patients with liver cirrhosis is complex and suboptimal, but no clinical trial has adequately investigated antidiabetic drug use for such patients. We evaluate the risk of mortality, cardiovascular events, and hepatic outcomes between dipeptidyl peptidase-4 (DPP-4) inhibitor users and nonusers in patients with type 2 diabetes mellitus (T2DM) and cirrhosis.

Methods

We selected 2828 paired propensity score matched DPP-4 inhibitor users and nonusers from a cohort of T2DM with compensated liver cirrhosis between January 1, 2007, and December 31, 2012. Cox proportional hazards models were used to assess the risk of main outcomes for DPP-4 inhibitor users.

Results

The incidence rate of decompensated cirrhosis during follow-up was 2.20 and 1.53 per 100 patient-years (adjusted hazard ratio [aHR] 1.35, 95% confidence interval [CI] 1.03–1.77) for DPP-4 inhibitor users and nonusers, respectively. The aHRs (95% CI) of variceal bleeding and hepatic failure were 1.67 (1.11–2.52) and 1.35 (1.02–1.79), respectively, for DPP-4 inhibitor users over nonusers. The risk of all-cause mortality, hepatocellular carcinoma, and major cardiovascular events between DPP-4 inhibitor users and nonusers were not statistically different.

Conclusions

This study found that DPP-4 inhibitor users were associated with higher risks of decompensated cirrhosis and hepatic failure than did nonusers among patients with T2DM and compensated liver cirrhosis. We must continue to search for appropriate antidiabetic drugs for patients with liver cirrhosis.

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Acknowledgements

This manuscript was edited by Wallace Academic Editing.

Funding

This study was partially supported by the Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW109-TDU-B-212-114004), Ministry of Science and Technology Clinical Trial Consortium for Stroke (MOST 108-2321-B-039-003-), and the Tseng-Lien Lin Foundation, Taichung, Taiwan. The writing or preparation of this paper was not funded by any organization; the data analyses were not undertaken by individuals who are employees of funders, or any author who received funding from funders; no writing support was from the funders. The corresponding authors had complete access to all data in the study and had final responsibility for the decision to submit for publication.

Author information

Authors and Affiliations

  1. Dr. Yen’s Clinic, No. 15, Shanying Road, Gueishan District, Taoyuan, 33354, Taiwan

    Fu-Shun Yen

  2. Division of Allergy, Immunology and Rheumatology Chung, Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City, 40201, Taiwan

    James Cheng-Chung Wei

  3. Management Office for Health Data, China Medical University Hospital, 3F., No. 373-2, Jianxing Road, Taichung, 40459, Taiwan

    Hei-Tung Yip

  4. College of Medicine, China Medical University, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City, 40201, Taiwan

    Hei-Tung Yip

  5. Faculty of Medicine, National Yang-Ming University School of Medicine, No. 155, Sec.2, Linong Street, Taipei, 11221, Taiwan

    Chii-Min Hwu & Ming-Chih Hou

  6. Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei, 11217, Taiwan

    Chii-Min Hwu

  7. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei, 11217, Taiwan

    Ming-Chih Hou

  8. Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County, 35053, Taiwan

    Chih-Cheng Hsu

  9. Department of Family Medicine, Min-Sheng General Hospital, 168 ChingKuo Road, Taoyuan, 33044, Taiwan

    Chih-Cheng Hsu

  10. Department of Health Services Administration, China Medical University, No. 91, Xueshi Rd., North Dist., Taichung, 40402, Taiwan

    Chih-Cheng Hsu

Authors
  1. Fu-Shun Yen
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  2. James Cheng-Chung Wei
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  3. Hei-Tung Yip
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  4. Chii-Min Hwu
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  5. Ming-Chih Hou
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  6. Chih-Cheng Hsu
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Contributions

Conceptualization: FSY, CMH, MCH and CCH; Methodology: JCW and CMH; Software: HTY; Validation: MCH and CCH; Formal analysis: HTY; Investigation: FSY and MCH; Resources: JCW; Data curation: CCH; Writing—original draft preparation: FSY; Writing—review and editing: MCH and CCH; Visualization: JCW; Supervision: CCH; Project administration: CMH; Funding acquisition: HTY. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Ming-Chih Hou or Chih-Cheng Hsu.

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Conflicts of interest

The authors declare no conflict of interest.

Ethical standards

This study was approved by the Research Ethics Committee of China Medical University and Hospital (CMUH104-REC2-115). All information identifying care providers or patients was encrypted, and we were permitted to waive informed consent.

Informed consent

To protect individual privacy, all patient or caregiver data were scrambled before being released. This study was approved by the Research Ethics Committee of China Medical University and Hospital (CMUH104-REC2-115-CR-4) and was exempted from informed consent requirements.

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Yen, FS., Wei, J.CC., Yip, HT. et al. Dipeptidyl peptidase-4 inhibitors may accelerate cirrhosis decompensation in patients with diabetes and liver cirrhosis: a nationwide population-based cohort study in Taiwan. Hepatol Int 15, 179–190 (2021). https://doi.org/10.1007/s12072-020-10122-1

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  • DOI: https://doi.org/10.1007/s12072-020-10122-1

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