No pancreatic safety concern following glucagon-like peptide-1 receptor agonist therapies: A pooled analysis of cardiovascular outcome trials

Diabetes Metab Res Rev. 2018 Nov;34(8):e3061. doi: 10.1002/dmrr.3061. Epub 2018 Sep 14.

Abstract

Aims: Evidence on the pancreatic safety of glucagon-like peptide-1 receptor agonist therapy has been limited. The objective of the study was to investigate this issue by pooling data on the incidence of acute pancreatitis and pancreatic cancer from four large-scale cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists.

Materials and methods: Data were extracted from four published cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes, and pooled analysis was performed to evaluate the risk of acute pancreatitis and pancreatic cancer associated with glucagon-like peptide-1 receptor agonist treatment. Peto OR with 95% CI was used for risk evaluation.

Results: The four cardiovascular outcome trials enrolled a total of 33 457 patients with type 2 diabetes and reported 123 patients with acute pancreatitis and 70 patients with pancreatic cancer during the median follow-ups of 2.1 to 3.8 years. There was no increased risk of either acute pancreatitis (Peto OR 0.89 [95% CI 0.63, 1.27]) or pancreatic cancer (Peto OR 0.84 [95% CI 0.53, 1.35]) associated with glucagon-like peptide-1 receptor agonists compared with placebo when added to standard care.

Conclusions: Combined analysis of the four cardiovascular outcome trials showed that treatment with glucagon-like peptide-1 receptor agonists was not associated with an increased risk of either acute pancreatitis or pancreatic cancer in patients with type 2 diabetes. Our new analysis further supports the previously reported results.

Keywords: acute pancreatitis; glucagon-like peptide-1 receptor agonist; pancreatic cancer; type 2 diabetes.

Publication types

  • Meta-Analysis

MeSH terms

  • Acute Disease
  • Aged
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control
  • Cardiovascular System / drug effects
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetic Angiopathies / epidemiology*
  • Diabetic Angiopathies / prevention & control*
  • Female
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Incidence
  • Male
  • Middle Aged
  • Pancreas / drug effects*
  • Pancreas / pathology
  • Pancreatic Neoplasms / chemically induced
  • Pancreatic Neoplasms / epidemiology
  • Pancreatitis / chemically induced
  • Pancreatitis / epidemiology
  • Treatment Outcome

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents