Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study

JAMA Intern Med. 2013 Apr 8;173(7):534-9. doi: 10.1001/jamainternmed.2013.2720.

Abstract

Importance: Acute pancreatitis has significant morbidity and mortality. Previous studies have raised the possibility that glucagonlike peptide 1 (GLP-1)-based therapies, including a GLP-1 mimetic (exenatide) and a dipeptidyl peptidase 4 inhibitor (sitagliptin phosphate), may increase the risk of acute pancreatitis.

Objective: To test whether GLP-1-based therapies such as exenatide and sitagliptin are associated with an increased risk of acute pancreatitis. We used conditional logistic regression to analyze the data.

Design: Population-based case-control study.

Setting: A large administrative database in the United States from February 1, 2005, through December 31, 2008.

Participants: Adults with type 2 diabetes mellitus aged 18 to 64 years. We identified 1269 hospitalized cases with acute pancreatitis using a validated algorithm and 1269 control subjects matched for age category, sex, enrollment pattern, and diabetes complications.

Main outcome measure: Hospitalization for acute pancreatitis.

Results: The mean age of included individuals was 52 years, and 57.45% were male. Cases were significantly more likely than controls to have hypertriglyceridemia (12.92% vs 8.35%), alcohol use (3.23% vs 0.24%), gallstones (9.06% vs 1.34), tobacco abuse (16.39% vs 5.52%), obesity (19.62% vs 9.77%), biliary and pancreatic cancer (2.84% vs 0%), cystic fibrosis (0.79% vs 0%), and any neoplasm (29.94% vs 18.05%). After adjusting for available confounders and metformin hydrochloride use, current use of GLP-1-based therapies within 30 days (adjusted odds ratio, 2.24 [95% CI, 1.36-3.68]) and recent use past 30 days and less than 2 years (2.01 [1.37-3.18]) were associated with significantly increased odds of acute pancreatitis relative to the odds in nonusers.

Conclusions and relevance: In this administrative database study of US adults with type 2 diabetes mellitus, treatment with the GLP-1-based therapies sitagliptin and exenatide was associated with increased odds of hospitalization for acute pancreatitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Exenatide
  • Female
  • Glucagon-Like Peptide 1 / adverse effects*
  • Hospitalization*
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Pancreatitis / chemically induced*
  • Pancreatitis / therapy
  • Peptides / adverse effects
  • Pyrazines / adverse effects
  • Risk Factors
  • Sitagliptin Phosphate
  • Triazoles / adverse effects
  • Venoms / adverse effects

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Peptides
  • Pyrazines
  • Triazoles
  • Venoms
  • Glucagon-Like Peptide 1
  • Exenatide
  • Sitagliptin Phosphate