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

Gastroenterology. 2011 Jul;141(1):150-6. doi: 10.1053/j.gastro.2011.02.018. Epub 2011 Feb 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Webcast

MeSH terms

  • Adverse Drug Reaction Reporting Systems
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects*
  • Exenatide
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Odds Ratio
  • Pancreatic Neoplasms / chemically induced*
  • Pancreatic Neoplasms / epidemiology
  • Pancreatitis / chemically induced*
  • Pancreatitis / epidemiology
  • Peptides / adverse effects*
  • Pyrazines / adverse effects*
  • Receptors, Glucagon / agonists*
  • Risk Assessment
  • Risk Factors
  • Sitagliptin Phosphate
  • Thyroid Neoplasms / chemically induced*
  • Thyroid Neoplasms / epidemiology
  • Triazoles / adverse effects*
  • United States / epidemiology
  • United States Food and Drug Administration
  • Venoms / adverse effects*


  • Dipeptidyl-Peptidase IV Inhibitors
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Peptides
  • Pyrazines
  • Receptors, Glucagon
  • Triazoles
  • Venoms
  • Exenatide
  • Sitagliptin Phosphate