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Effect of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on colorectal cancer incidence and its precursors

  • Pharmacoepidemiology and Prescription
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Abstract

Aims

Incretin-based antihyperglycemic therapies increase intestinal mucosal expansion and polyp growth in mouse models. We aimed to evaluate the effect of dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1ra) initiation on colorectal cancer incidence.

Methods

We conducted a cohort study on US Medicare beneficiaries over age 66 from 2007 to 2013 without prevalent cancer. We identified three active-comparator and new-user cohorts: DPP-4i versus thiazolidinediones (TZD), DPP-4i versus sulphonylureas (SU), and GLP-1ra versus long acting insulin (LAI). Follow-up started from 6 months post-second prescription and ended 6 months after stopping (primary as-treated analysis). We estimated hazard ratios (HR) and 95 % confidence intervals (CI) for incident colorectal cancer adjusting for measured confounders using propensity score weighting.

Results

The median duration of treatment ranged 0.7–0.9 years among DPP-4i cohorts. Based on 104 events among 39,334 DPP-4i and 63 events among 25,786 TZD initiators, there was no association between DPP-4i initiation and colorectal cancer (adjusted HR = 1.17 (CI 0.88, 1.71)). There were 73 events among 27,047 DPP-4i and 266 events among 76,012 SU initiators with the adjusted HR 0.98 (CI 0.74, 1.30). We identified 5600 GLP-1ra and 54,767 LAI initiators and the median duration of treatment was 0.8 and 1.2 years, respectively. The adjusted HR was 0.82 (CI 0.42, 1.58) based on <11 events among GLP-1ra versus 276 events among LAI initiators.

Conclusion

Although limited by the short duration of treatment, our analyses based on real-world drug utilization patterns provide evidence of no short-term effect of incretin-based agents on colorectal cancer.

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Authors and Affiliations

  1. Department of Epidemiology, University of North Carolina at Chapel Hill, Gillings School of Global Public Health, Campus Box 7435, 2101 McGavran-Greenberg Hall, Chapel Hill, NC, USA

    Phyo T. Htoo, Mugdha Gokhale, Virginia Pate & Til Stürmer

  2. Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA

    John B. Buse

  3. Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    M. Alison Marquis

Authors
  1. Phyo T. Htoo
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Corresponding author

Correspondence to Til Stürmer.

Ethics declarations

This retrospective large database study was approved by the University of North Carolina at Chapel Hill Institutional Review Board. For this type of study, formal consent is not required.

Funding

This study was not funded. The database infrastructure used for this project was funded by the Pharmacoepidemiology Gillings Innovation Lab (PEGIL) for the Population-Based Evaluation of Drug Benefits and Harms in Older US Adults (GIL200811.0010), the Center for Pharmacoepidemiology, Department of Epidemiology, UNC Gillings School of Global Public Health, the CER Strategic Initiative of UNC’s Clinical Translational Science Award (UL1TR001111), the Cecil G. Sheps Center for Health Services Research, UNC, and the UNC School of Medicine.

Conflict of interest

TS receives investigator-initiated research funding and support as Principal Investigator (R01 AG023178) from the National Institute on Aging (NIA), and as Co-Investigator (R01 CA174453; R01 HL118255, R21-HD080214), National Institutes of Health (NIH). He also receives salary support as Director of the Comparative Effectiveness Research (CER) Strategic Initiative, NC Translational and Clinical Sciences (TraCS) Institute, UNC Clinical and Translational Science Award (UL1TR001111) and as Director of the Center for Pharmacoepidemiology (current members: GlaxoSmithKline, UCB BioSciences, Merck) and research support from pharmaceutical companies (Amgen, AstraZeneca) to the Department of Epidemiology, University of North Carolina at Chapel Hill. Dr. Stürmer does not accept personal compensation of any kind from any pharmaceutical company. He owns stock in Novartis, Roche, BASF, AstraZeneca, Johnson & Johnson, and Novo Nordisk.

M. M. has received salary support from research grants from Pfizer, Sanofi, and Medtronic and receives salary support from the Comparative Effectiveness Research (CER) Strategic Initiative, NC TraCS Institute, UNC Clinical and Translational Science Award (UL1TR001111).

V.P. receives salary support from investigator-initiated grants from Merck and Amgen and from the Comparative Effectiveness Research (CER) Strategic Initiative, NC TraCS Institute, UNC Clinical and Translational Science Award (UL1TR001111).

J.B. is supported by the NIH (UL1TR000083 and R01HL110380). He is an investigator and/or consultant without any direct financial benefit to him under contracts between his employer and the following companies: Amylin Pharmaceuticals, Inc., Andromeda, Astellas, AstraZeneca, Boehringer Ingelheim GmbH & Co. KG, Bristol-Myers Squibb Company, Dance Biopharm, Elcelyx Therapeutics, Inc., Eli Lilly and Company, GI Dynamics, GlaxoSmithKline, Halozyme Therapeutics, F. Hoffmann-La Roche, Ltd., Intarcia Therapeutics, Johnson & Johnson, Lexicon, LipoScience, Macrogenics, Medtronic, Merck, Metavention, Novo Nordisk, Orexigen Therapeutics, Inc., Osiris Therapeutics, Inc., Pfizer, Inc., PhaseBio Pharmaceuticals Inc., Quest Diagnostics, Sanofi, Scion neuroStim, Takeda, ToleRx, vTv Pharmaceuticals. He has stock options and has received payments from PhaseBio.

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Htoo, P.T., Buse, J.B., Gokhale, M. et al. Effect of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on colorectal cancer incidence and its precursors. Eur J Clin Pharmacol 72, 1013–1023 (2016). https://doi.org/10.1007/s00228-016-2068-3

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