title: Incretin-mimetic therapies and pancreatic disease: a review of observational data.
abstract: OBJECTIVE
  Signals from the FDA Adverse Event Reporting System (AERS) and pre-clinical and human pancreata obtained from organ donors have suggested that incretin-based therapies used to treat type 2 diabetes mellitus, such as glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, may increase the risk of acute pancreatitis (AP) and pancreatic cancer (PC). However, data from observational studies and randomized trials have been conflicting. We conducted a literature review to identify and summarize all observational data published assessing the pancreatic safety of incretins.
  
  
  METHODS
  Searches were conducted in MEDLINE via PubMed and Embase using the key terms for the time period of 1 January 2005, to 12 February 2014. A total of 180 articles were screened in abstract form and 49 were subsequently reviewed in full text for inclusion. Data from 12 articles are included in this report.
  
  
  RESULTS
  Data from the FDA AERS database suggest increased risk of AP and PC with GLP-1 receptor agonist and DPP-4 inhibitor use. These findings are not supported by population-based observational studies for either AP or PC; however, studies assessing the relationship between PC and incretin-based therapies are limited.
  
  
  CONCLUSIONS
  Current evidence is conflicting and inadequate to conclude whether use of incretin-based therapies increases the risk of AP and PC. Further studies, with the ability to provide long term follow-up, are needed.
authors.affiliation: Department of Epidemiology, New England Research Institutes Inc. , Watertown, MA , USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Suarez
authors.forename: Carol E
authors.initials: CE
authors.lastname: Koro
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Christian
authors.forename: Alicia D
authors.initials: AD
authors.lastname: Spector
authors.forename: Andre B
authors.initials: AB
authors.lastname: Araujo
authors.forename: Sybil
authors.initials: S
authors.lastname: Abraham
mesh_terms: D000208:Acute Disease; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D015994:Incidence; D054795:Incretins / Q000627:therapeutic use*; D064887:Observational Studies as Topic; D010190:Pancreatic Neoplasms / Q000453:epidemiology*; D010195:Pancreatitis / Q000453:epidemiology*; D018027:Receptors, Glucagon / Q000819:agonists* / Q000627:therapeutic use
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D054795:Incretins; D018027:Receptors, Glucagon
keywords: Acute pancreatitis; Incretin therapies; Pancreatic cancer; Type 2 diabetes