The potential risks of pancreatitis and pancreatic cancer with GLP-1-based therapies are far outweighed by the proven and potential (cardiovascular) benefits

Diabet Med. 2013 Oct;30(10):1148-55. doi: 10.1111/dme.12301.

Abstract

Recent suggestions that glucagon-like peptide-1 (GLP-1)-based therapies could cause pancreatitis, and even pancreatic cancer, are based on:

Animal studies: The worrying histological changes are not reproduced in all studies and are unexpectedly variable with different GLP-1-based therapies.

An observational study: Singh's findings that pancreatitis is doubled with GLP-1-based therapies could relate to their use in obese patients who are prone to pancreatitis risk factors--gallstones and hypertriglyceridaemia. The other observational studies do not find an association between GLP-1-based therapies and pancreatitis.

Us food and drug administration adverse event reporting system: The increased reports of pancreatitis and pancreatic cancer are likely to be attributable to 'notoriety bias'.

A study of organ donor pancreases: Butler's findings for those on GLP-1-based therapies vs. those not, could have other explanations. Meanwhile: META ANALYSIS: Randomized control trials with GLP-1-based therapies do not find increased pancreatitis risk. Meta-analysis of 53 randomized controlled trials including 20 212 dipeptidyl peptidase-4 inhibitor-treated patients found a significantly reduced risk of major adverse cardiovascular events [odds ratio 0.689 (0.528-0.899), P = 0.006] for dipeptidyl peptidase-4 inhibitors compared with control subjects.

Cardiovascular risk: The evidence suggests that there is more than a possibility that some of the GLP-1 receptor agonists, and possibly also some dipeptidyl peptidase-4 inhibitors, may be associated with reduced cardiovascular events. Eight ongoing long-term cardiovascular randomized controlled trials will report from September 2013 onwards. These trials should resolve the issue of pancreatitis risk and substantiate the extent of benefit.

Conclusion: Whilst we should remain vigilant, currently the balance of evidence is strongly in support of GLP-1-based therapy, with benefits far outweighing potential risks.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Adverse Drug Reaction Reporting Systems
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetic Angiopathies / prevention & control
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Exenatide
  • Female
  • Glucagon-Like Peptide 1 / adverse effects
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / therapeutic use
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Incretins / adverse effects
  • Incretins / therapeutic use*
  • Liraglutide
  • Male
  • Pancreatic Neoplasms / chemically induced*
  • Pancreatic Neoplasms / pathology
  • Pancreatitis / chemically induced*
  • Pancreatitis / pathology
  • Patient Selection
  • Peptides / adverse effects
  • Peptides / therapeutic use
  • Randomized Controlled Trials as Topic
  • Receptors, Glucagon / agonists*
  • Risk Assessment
  • Risk Factors
  • Venoms / adverse effects
  • Venoms / therapeutic use

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Incretins
  • Peptides
  • Receptors, Glucagon
  • Venoms
  • lixisenatide
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Exenatide