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Pancreatitis, Pancreatic, and Thyroid Cancer With Glucagon-Like Peptide-1–Based Therapies

  • Michael Elashoff
    Affiliations
    Larry L. Hillblom Islet Research Center at David Geffen School of Medicine and Department of Biomathematics, University of California, Los Angeles, California
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  • Aleksey V. Matveyenko
    Affiliations
    Larry L. Hillblom Islet Research Center at David Geffen School of Medicine and Department of Biomathematics, University of California, Los Angeles, California
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  • Belinda Gier
    Affiliations
    Larry L. Hillblom Islet Research Center at David Geffen School of Medicine and Department of Biomathematics, University of California, Los Angeles, California
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  • Robert Elashoff
    Affiliations
    Larry L. Hillblom Islet Research Center at David Geffen School of Medicine and Department of Biomathematics, University of California, Los Angeles, California
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  • Peter C. Butler
    Correspondence
    Reprint requests Address requests for reprints to: Peter C. Butler MD, Larry L. Hillblom Islet Research Center, David Geffen School of Medicine at UCLA, 900 Veteran Avenue, 24-130 Warren Hall, Los Angeles, California 90095-7073. fax: (310) 206-5368
    Affiliations
    Larry L. Hillblom Islet Research Center at David Geffen School of Medicine and Department of Biomathematics, University of California, Los Angeles, California
    Search for articles by this author
Published:February 21, 2011DOI:https://doi.org/10.1053/j.gastro.2011.02.018

      Background & Aims

      Glucagon-like peptide-1−based therapy is gaining widespread use for type 2 diabetes, although there are concerns about risks for pancreatitis and pancreatic and thyroid cancers. There are also concerns that dipeptidyl peptidase-4 inhibitors could cause cancer, given their effects on immune function.

      Methods

      We examined the US Food and Drug Administration's database of reported adverse events for those associated with the dipeptidyl peptidase−4 inhibitor sitagliptin and the glucagon-like peptide-1 mimetic exenatide, from 2004−2009; data on adverse events associated with 4 other medications were compared as controls. The primary outcomes measures were rates of reported pancreatitis, pancreatic and thyroid cancer, and all cancers associated with sitagliptin or exenatide, compared with other therapies.

      Results

      Use of sitagliptin or exenatide increased the odds ratio for reported pancreatitis 6-fold as compared with other therapies (P < 2 × 10−16). Pancreatic cancer was more commonly reported among patients who took sitagliptin or exenatide as compared with other therapies (P < .008, P < 9 × 10−5). All other cancers occurred similarly among patients who took sitagliptin compared with other therapies (P =.20).

      Conclusions

      These data are consistent with case reports and animal studies indicating an increased risk for pancreatitis with glucagon-like peptide-1−based therapy. The findings also raise caution about the potential long-term actions of these drugs to promote pancreatic cancer.

      Keywords

      Abbreviations used in this paper:

      AERS (adverse event reporting system), CI (confidence interval), DPP-4 (dipeptidyl peptidase-4), FDA (Food and Drug Administration), GLP-1 (glucagon-like peptide-1), OR (odds ratio)
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      Linked Article

      • Pro- or Anti-inflammatory Properties of the Adipokine Dipeptidyl Peptidase-4?
        GastroenterologyVol. 141Issue 6
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          In the July 2011 issue of Gastroenterology, Elashoff et al1 reported an increased incidence of pancreatitis in diabetic subjects undergoing glucagon-like peptide (GLP)-1–based therapies. In light of the recently emerging and proliferating discussion about the clinical use and the associated risks of incretin-based therapies, we would like to comment on this article and contribute evidence supporting the role of adipose-derived dipeptidyl peptidase (DPP)-4 in the context of the metabolic syndrome.
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