Association between incretin-based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: A large population-based matched cohort study

Aim: To examine the association between the use of incretin-based drugs [glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors (DPP-4Is)] and the risk of cholangiocarcinoma (CCA) in the United States. Methods: This large population-based, retrospective cohort study...

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Main Authors: Arunkumar Krishnan, Carolin V. Schneider, Hendrik-Tobias Arkenau, Ezequiel Matias Mauro, Alejandro Forner, W. Scott Butsch, Declan Walsh, Saleh A. Alqahtani
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Journal of Clinical & Translational Endocrinology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2214623724000413
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author Arunkumar Krishnan
Carolin V. Schneider
Hendrik-Tobias Arkenau
Ezequiel Matias Mauro
Alejandro Forner
W. Scott Butsch
Declan Walsh
Saleh A. Alqahtani
author_facet Arunkumar Krishnan
Carolin V. Schneider
Hendrik-Tobias Arkenau
Ezequiel Matias Mauro
Alejandro Forner
W. Scott Butsch
Declan Walsh
Saleh A. Alqahtani
author_sort Arunkumar Krishnan
collection DOAJ
description Aim: To examine the association between the use of incretin-based drugs [glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors (DPP-4Is)] and the risk of cholangiocarcinoma (CCA) in the United States. Methods: This large population-based, retrospective cohort study using the TriNetX datasets included adult patients with type 2 diabetes mellitus (T2DM) who were new users of GLP-1RAs, DPP-4Is, or other second- or third-line antidiabetic drugs between 2010 and 2021. The primary outcome was the incidence of CCA. Results: A total of 3,816,071 patients were included (mean age, 61.4 years, female, 49.3 %). A 51 % and 23 % risk reduction in CCA after 1 year of exposure to GLP-1RAs (hazard ratio 0.49; 95 % CI 0.40–0.60) and DPP4Is (0.77, 95 % CI 0.67–0.90), respectively compared to new second-or third-line users. Results were consistent at 3, 5, and 7 years of follow-up (0.66, 0.71, and 0.72 for GLP-1RAs and 0.84, 0.87, and 0.85 for DPP-4Is, respectively). Compared to new metformin users, GLP-1RA users were associated with a 42 % lower risk of developing CCA, whereas DPP-4I group was not associated with an increased risk. Conclusions: GLP-1RAs and DPP-4Is were not associated with a significantly increased risk of CCA. GLP-1RAs even showed a reduced risk of CCA development. They can be considered as safe and effective treatment options for patients with T2DM at risk of CCA.
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spelling doaj-art-7692fc64b12440d7bb080c8ee48909832025-08-20T02:34:19ZengElsevierJournal of Clinical & Translational Endocrinology2214-62372024-12-013810037010.1016/j.jcte.2024.100370Association between incretin-based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: A large population-based matched cohort studyArunkumar Krishnan0Carolin V. Schneider1Hendrik-Tobias Arkenau2Ezequiel Matias Mauro3Alejandro Forner4W. Scott Butsch5Declan Walsh6Saleh A. Alqahtani7Department of Supportive Oncology, Atrium Health Levine Cancer, Charlotte, NC, USA; Department of Medicine, Section of Hematology and Oncology, Wake Forest University School of Medicine, Winston Salem, NC, USA; Corresponding author at: The Center for Supportive Oncology, Levine Cancer Institute, Atrium Health, 1021 Morehead Medical Drive, Suite 70100, Charlotte, NC 28204, USA.Department of Internal Medicine III, RWTH Aachen University, Aachen, GermanySarah Cannon Research Institute, Cancer Institute, University College London, London, UKBarcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, SpainBarcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, SpainBariatric and Metabolic Institute, Cleveland Clinic, Cleveland, OH, USADepartment of Supportive Oncology, Atrium Health Levine Cancer, Charlotte, NC, USAOrgan Transplant Center of Excellence, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia; Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY, USAAim: To examine the association between the use of incretin-based drugs [glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors (DPP-4Is)] and the risk of cholangiocarcinoma (CCA) in the United States. Methods: This large population-based, retrospective cohort study using the TriNetX datasets included adult patients with type 2 diabetes mellitus (T2DM) who were new users of GLP-1RAs, DPP-4Is, or other second- or third-line antidiabetic drugs between 2010 and 2021. The primary outcome was the incidence of CCA. Results: A total of 3,816,071 patients were included (mean age, 61.4 years, female, 49.3 %). A 51 % and 23 % risk reduction in CCA after 1 year of exposure to GLP-1RAs (hazard ratio 0.49; 95 % CI 0.40–0.60) and DPP4Is (0.77, 95 % CI 0.67–0.90), respectively compared to new second-or third-line users. Results were consistent at 3, 5, and 7 years of follow-up (0.66, 0.71, and 0.72 for GLP-1RAs and 0.84, 0.87, and 0.85 for DPP-4Is, respectively). Compared to new metformin users, GLP-1RA users were associated with a 42 % lower risk of developing CCA, whereas DPP-4I group was not associated with an increased risk. Conclusions: GLP-1RAs and DPP-4Is were not associated with a significantly increased risk of CCA. GLP-1RAs even showed a reduced risk of CCA development. They can be considered as safe and effective treatment options for patients with T2DM at risk of CCA.http://www.sciencedirect.com/science/article/pii/S2214623724000413IncretinGlucagon-like peptide-1 receptor agonistsCholangiocarcinomaDipeptidyl peptidase 4 inhibitorsType 2 diabetes mellitus
spellingShingle Arunkumar Krishnan
Carolin V. Schneider
Hendrik-Tobias Arkenau
Ezequiel Matias Mauro
Alejandro Forner
W. Scott Butsch
Declan Walsh
Saleh A. Alqahtani
Association between incretin-based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: A large population-based matched cohort study
Journal of Clinical & Translational Endocrinology
Incretin
Glucagon-like peptide-1 receptor agonists
Cholangiocarcinoma
Dipeptidyl peptidase 4 inhibitors
Type 2 diabetes mellitus
title Association between incretin-based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: A large population-based matched cohort study
title_full Association between incretin-based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: A large population-based matched cohort study
title_fullStr Association between incretin-based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: A large population-based matched cohort study
title_full_unstemmed Association between incretin-based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: A large population-based matched cohort study
title_short Association between incretin-based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: A large population-based matched cohort study
title_sort association between incretin based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes a large population based matched cohort study
topic Incretin
Glucagon-like peptide-1 receptor agonists
Cholangiocarcinoma
Dipeptidyl peptidase 4 inhibitors
Type 2 diabetes mellitus
url http://www.sciencedirect.com/science/article/pii/S2214623724000413
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