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Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies

Michael Elashoff1, Aleksey V Matveyenko, Belinda Gier

  • 1Larry L. Hillblom Islet Research Center at David Geffen School of Medicine and Department of Biomathematics, University of California, Los Angeles, California 90095-7073, USA.

Gastroenterology
|February 22, 2011
PubMed
Abstract

Insights

Glucagon-like peptide-1 therapies like exenatide and sitagliptin were linked to a sixfold increased risk of pancreatitis and higher rates of pancreatic cancer. Further research is needed to understand the long-term effects of these type 2 diabetes drugs.

Area of Science:

  • Endocrinology
  • Pharmacology
  • Oncology

Background:

  • Glucagon-like peptide-1 (GLP-1) based therapies are increasingly used for type 2 diabetes management.
  • Concerns exist regarding potential risks, including pancreatitis and various cancers, associated with GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors.

Purpose of the Study:

  • To investigate the association between GLP-1 based therapies (sitagliptin, exenatide) and adverse events, specifically pancreatitis and pancreatic cancers.
  • To compare the rates of these adverse events with other medications using a large adverse event database.

Main Methods:

  • Analysis of the US Food and Drug Administration's adverse event reporting system database from 2004-2009.
  • Comparison of reported pancreatitis, pancreatic cancer, thyroid cancer, and all cancer rates for sitagliptin and exenatide against four control medications.

Main Results:

  • Sitagliptin and exenatide use was associated with a 6-fold increased odds ratio for reported pancreatitis compared to controls (P<2×10(-16)).
  • Pancreatic cancer reporting rates were significantly higher in patients using sitagliptin or exenatide versus controls (P<.008, P<9×10(-5)).
  • No significant difference in other cancer occurrences was observed between sitagliptin users and controls (P=.20).

Conclusions:

  • Findings support existing data suggesting an increased risk of pancreatitis with GLP-1 based therapies.
  • The results warrant caution regarding the potential long-term risk of pancreatic cancer associated with these diabetes medications.

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