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Cited by 120Pancreatic and Hepatic Oncology ResearchDiabetes Treatment and ManagementMetabolism, Diabetes, and Cancer

Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study

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Azoulay, Laurent, Filion, Kristian B, Platt, Robert W, Dahl, Matthew, Dormuth, Colin R, Clemens, Kristin K, Durand, Madeleine, Juurlink, David N +4 more·2016·BMJ
DOI 10.1136/bmj.i581PMC PMC4772785
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Abstract

OBJECTIVE: To determine whether the use of incretin based drugs compared with sulfonylureas is associated with an increased risk of incident pancreatic cancer in people with type 2 diabetes. DESIGN: Population based cohort. SETTING: Large, international, multicentre study combining the health records from six participating sites in Canada, the United States, and the United Kingdom. PARTICIPANTS: A cohort of 972,384 patients initiating antidiabetic drugs between 1 January 2007 and 30 June 2013, with follow-up until 30 June 2014. MAIN OUTCOME MEASURES: Within each cohort we conducted nested case-control analyses, where incident cases of pancreatic cancer were matched with up to 20 controls on sex, age, cohort entry date, duration of treated diabetes, and duration of follow-up. Hazard ratios and 95% confidence intervals for incident pancreatic cancer were estimated, comparing use of incretin based drugs with use of sulfonylureas, with drug use lagged by one year for latency purposes. Secondary analyses assessed whether the risk varied by class (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) or by duration of use (cumulative duration of use and time since treatment initiation). Site specific hazard ratios were pooled using random effects models. RESULTS: During 2,024,441 person years of follow-up (median follow-up ranging from 1.3 to 2.8 years; maximum 8 years), 1221 patients were newly diagnosed as having pancreatic cancer (incidence rate 0.60 per 1000 person years). Compared with sulfonylureas, incretin based drugs were not associated with an increased risk of pancreatic cancer (pooled adjusted hazard ratio 1.02, 95% confidence interval 0.84 to 1.23). Similarly, the risk did not vary by class and evidence of a duration-response relation was lacking. CONCLUSIONS: In this large, population based study the use of incretin based drugs was not associated with an increased risk of pancreatic cancer compared with sulfonylureas. Although this potential adverse drug reaction will need to be monitored long term owing to the latency of the cancer, these findings provide some reassurance on the safety of incretin based drugs.

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  • Despite limitations of real-world observational studies, researchers offer confidence regarding the pancreatic safety profiles of GLP-1 RAs.

    “Despite the limitations of real-world observational studies—including the absence of randomization, control for confounding variables, and inability to establish causality—researches offer confidence regarding the pancreatic safety profiles of GLP-1 RAs [55,61].”

    From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [55]

    The Discussion’s Conclusions and implications section says the findings provide “some reassurance” about pancreatic cancer risk, including results consistent by drug class. The Results section reports an imprecise GLP-1 receptor agonist estimate, and the paper calls for continued surveillance. It does not establish a broad pancreatic safety profile; moreover, the Strengths and limitations section says the study adjusted for measured confounders, although residual confounding remained possible. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Initial concerns regarding a possible link between GLP-1 RAs and the development of pancreatitis or pancreatic cancer have not been supported by the results of RCTs or real-world data.

    “Initial concerns regarding the possible link between the use of GLP-1 RAs and the development of pancreatitis or pancreatic cancer have not been supported by the results of RCTs [53,54], or real-world data [29,55,56].”

    From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [55]

    The Results report no increased pancreatic cancer risk for GLP-1 receptor agonists compared with sulfonylureas (adjusted hazard ratio 1.13, 95% CI 0.38 to 3.38), supporting the real-world-data part of the claim. This study assessed pancreatic cancer, not whether GLP-1 receptor agonists cause pancreatitis. The Discussion also cautions that longer-term monitoring of cancer risk is needed. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Investigators from CNODES concluded that incretin-based medications did not correlate with an increased risk of acute pancreatitis or pancreatic cancer compared to other oral anti-diabetic agents, consistent across drug classification and duration of use.

    “Nonetheless, investigators from the Canadian Network for Observational Drug Effect Studies (CNODES) reported contradictory results. They concluded that incretin-based medications did not correlate with an increased risk of acute pancreatitis or pancreatic cancer compared to other oral anti-diabetic agents, which remained consistent across drug classification and duration of use [29,55].”

    From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [55]

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Authors
Azoulay, L., Filion, K. B., Platt, R. W., Dahl, M., Dormuth, C. R., Clemens, K. K., Durand, M., Juurlink, D. N., Targownik, L. E., Turin, T. C., Paterson, J. M., & Ernst, P.
Affiliations
  • Jewish General Hospital (CA)
  • McGill University Health Centre (CA)
  • University of Manitoba (CA)
  • University of British Columbia (CA)
  • Western University (CA)
  • Institute for Clinical Evaluative Sciences (CA)
  • University of Calgary (CA)
  • University of Toronto (CA)
Corresponding author
Azoulay, Laurent
ORCID
Venue
BMJ
Publisher
BMJ
Published
2016-02-17
Volume
352
Pages
i581
ISSN
1756-1833 (ISSN-L)
DOI
10.1136/bmj.i581
PMC
PMC4772785
OpenAlex
W2277579395
Cited by
120
References
5
Citations by year
2026: 9 · 2025: 10 · 2024: 8 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 15 · 2018: 25 · 2017: 15 · 2016: 14 · 2013: 1
FWCI
12.41
Type
journal article
Language
en
Open access
Licence
Locations
  • BMJ (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • eScholarship@McGill (McGill) (submittedVersion, cc-by-nc)
  • HighWire Press Open Archive (submittedVersion)
Funders
Canadian Institutes of Health Research (111845_1)
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • 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
incretin-based drugs, pancreatic cancer, type 2 diabetes, sulfonylureas, DPP-4 inhibitors, GLP-1 receptor agonists, drug safety, cancer risk, antidiabetic drugs
MeSH terms
Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Adult, Aged, Canada, Diabetes Mellitus, Type 2, Female, United Kingdom, Humans, Hypoglycemic Agents, Male, Middle Aged, Pancreatic Neoplasms, Retrospective Studies, Sulfonylurea Compounds, United States, Proportional Hazards Models, Case-Control Studies, Incretins, Dipeptidyl-Peptidase IV Inhibitors, Young Adult

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