Use of incretin-based drugs and risk of cholangiocarcinoma: Scandinavian cohort study
Open accessAbstract
Aims/hypothesis: Concerns have been raised regarding a potential association of use of the incretin-based drugs dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1)-receptor agonists with risk of cholangiocarcinoma. We examined this association in nationwide data from three countries. Methods: We used data from nationwide registers in Sweden, Denmark and Norway, 2007–2018, to conduct two cohort studies, one for DPP4 inhibitors and one for GLP-1-receptor agonists, to investigate the risk of incident cholangiocarcinoma compared with an active-comparator drug class (sulfonylureas). The cohorts included patients initiating treatment episodes with DPP4 inhibitors vs sulfonylureas, and GLP-1-receptor agonists vs sulfonylureas. We used Cox regression models, adjusted for potential confounders, to estimate hazard ratios from day 366 after treatment initiation to account for cancer latency. Results: The main analyses of DPP4 inhibitors included 1,414,144 person-years of follow-up from 222,577 patients receiving DPP4 inhibitors (median [IQR] follow-up time, 4.5 [2.6–7.0] years) and 123,908 patients receiving sulfonylureas (median [IQR] follow-up time, 5.1 [2.9–7.8] years) during which 350 cholangiocarcinoma events occurred. Use of DPP4 inhibitors, compared with sulfonylureas, was not associated with a statistically significant increase in risk of cholangiocarcinoma (incidence rate 26 vs 23 per 100,000 person-years; adjusted HR, 1.15 [95% CI 0.90, 1.46]; absolute rate difference 3 [95% CI -3, 10] events per 100,000 person-years). The main analyses of GLP-1-receptor agonists included 1,036,587 person-years of follow-up from 96,813 patients receiving GLP-1-receptor agonists (median [IQR] follow-up time, 4.4 [2.4–6.9] years) and 142,578 patients receiving sulfonylureas (median [IQR] follow-up time, 5.5 [3.2–8.1] years) during which 249 cholangiocarcinoma events occurred. Use of GLP-1-receptor agonists was not associated with a statistically significant increase in risk of cholangiocarcinoma (incidence rate 26 vs 23 per 100,000 person-years; adjusted HR, 1.25 [95% CI 0.89, 1.76]; absolute rate difference 3 [95% CI -5, 13] events per 100,000 patient-years). Conclusions/interpretation: In this analysis using nationwide data from three countries, use of DPP4 inhibitors and GLP-1-receptor agonists, compared with sulfonylureas, was not associated with a significantly increased risk of cholangiocarcinoma. Graphical abstract:
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Recent investigations have highlighted the association between various neoplasms, such as thyroid, breast, and cholangiocarcinoma, and GLP-1 RAs.
“Recent investigations have highlighted the association between various neoplasms, such as thyroid, breast, and cholangiocarcinoma, and GLP-1 RAs [105-107].”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [106]
The Introduction discusses a potential association between GLP-1 receptor agonists and cholangiocarcinoma, so this paper supports the cholangiocarcinoma part of the multi-citation sentence. Its Results and Discussion report no statistically significant increased risk, however, so it does not establish a positive association. This citation does not address the sentence’s thyroid or breast cancer examples. (LLM, conf=0.84)
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Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning
Kim, J. A., & Yoo, H. J. (2025) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2025.0242 · Cited by 71 · see citing works
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- Authors
- Ueda, P., Wintzell, V., Melbye, M., Eliasson, B., Svensson, A.-M., Franzén, S., Gudbjörnsdottir, S., Hveem, K., Jonasson, C., Svanström, H., & Pasternak, B.
- Affiliations
- Karolinska Institutet (SE)
- Statens Serum Institut (DK)
- University of Gothenburg (SE)
- Region Västra Götaland (SE)
- Norwegian University of Science and Technology (NO)
- Norwegian Institute of Public Health (NO)
- Corresponding author
- Ueda, Peter
- ORCID
- Venue
- Diabetologia
- Published
- 2021-07-13
- Volume
- 64
- Issue
- 10
- Pages
- 2204-2214
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC8423638
- OpenAlex
- W3178955427
- Cited by
- 31
- References
- 5
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 7 · 2023: 1 · 2022: 7
- FWCI
- 3.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Diabetologia (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- Funders
- Hjärt-Lungfonden
- Nordic cancer union
- Cancerfonden
- Karolinska Institutet
- Svenska Sällskapet för Medicinsk Forskning
- Topics
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- cholangiocarcinoma, incretin-based drugs, DPP-4 inhibitors, GLP-1 receptor agonists, sulfonylureas, drug safety, cancer risk, type 2 diabetes
- MeSH terms
- Glucagon-Like Peptide-1 Receptor Agonists, Aged, Aged, 80 and over, Bile Duct Neoplasms, Diabetes Mellitus, Type 2, Pharmaceutical Preparations, Female, Follow-Up Studies, Humans, Hypoglycemic Agents, Male, Middle Aged, Registries, Risk Factors, Scandinavian and Nordic Countries, Sulfonylurea Compounds, Incidence, Proportional Hazards Models, Cholangiocarcinoma, Incretins, Dipeptidyl-Peptidase IV Inhibitors
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