[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 54.163.129.96. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Original Investigation
October 2016

Association of Bile Duct and Gallbladder Diseases With the Use of Incretin-Based Drugs in Patients With Type 2 Diabetes Mellitus

Author Affiliations
  • 1Laboratory of Biostatistics, Epidemiology, and Public Health (Equipe d’Acceuil 2415), Faculty of Medicine, University of Montpellier, Montpellier, France
  • 2Department of Medical Pharmacology and Toxicology, Montpellier University Hospital, Montpellier, France
  • 3Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
  • 4Division of Endocrinology, Jewish General Hospital, Montreal, Quebec, Canada
  • 5Institut National de la Santé et de la Récherche Médicale (INSERM), Unité 1058, Faculty of Medicine, University Montpellier 1, Montpellier, France
  • 6Division of Gastroenterology, McGill University Health Centre, Montreal, Quebec, Canada
  • 7Department of Oncology, McGill University, Montreal, Quebec, Canada
JAMA Intern Med. 2016;176(10):1474-1481. doi:10.1001/jamainternmed.2016.1531
Abstract

Importance  The use of dipeptidyl-peptidase–4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) analogues—a group of drugs used in the management of type 2 diabetes mellitus—may be associated with an increased risk of bile duct and gallbladder disease. To date, no observational study has assessed this possible association.

Objective  To determine whether the use of DPP-4 inhibitors and GLP-1 analogues is associated with an increased risk of incident bile duct and gallbladder disease in patients with type 2 diabetes.

Design, Setting, and Participants  A population-based cohort study linked the United Kingdom Clinical Practice Research Datalink with the Hospital Episodes Statistics database, yielding a cohort of 71 369 patients, 18 years or older, initiating an antidiabetic drug (including oral and injectable agents) between January 1, 2007, and March 31, 2014.

Exposures  Current use of DPP-4 inhibitors and GLP-1 analogues (alone or in combination therapy) compared with current use of at least 2 oral antidiabetic drugs.

Main Outcomes and Measures  Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs of incident bile duct or gallbladder events (cholelithiasis, cholecystitis, cholangitis) causing hospitalization, comparing current use of DPP-4 inhibitors and GLP-1 analogues with current use of at least 2 oral antidiabetic drugs.

Results  During 227 994 person-years of follow-up, 853 of the 71 369 patients were hospitalized for bile duct and gallbladder disease (incidence rate per 1000 person-years, 3.7; 95% CI, 3.5-4.0). Current use of DPP-4 inhibitors was not associated with an increased risk of bile duct and gallbladder disease compared with current use of at least 2 oral antidiabetic drugs (3.6 vs 3.3 per 1000 person-years; adjusted HR, 0.99; 95% CI, 0.75-1.32). In contrast, the use of GLP-1 analogues was associated with an increased risk of bile duct and gallbladder disease compared with current use of at least 2 oral antidiabetic drugs (6.1 vs 3.3 per 1000 person-years; adjusted HR, 1.79; 95% CI, 1.21-2.67). In a secondary analysis, GLP-1 analogues were also associated with an increased risk of cholecystectomy (adjusted HR, 2.08; 95% CI, 1.08-4.02).

Conclusions and Relevance  The use of GLP-1 analogues was associated with an increased risk of bile duct and gallbladder disease. Physicians should be aware of this potential adverse event when prescribing these drugs.

×