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Association of bile duct and gallbladder diseases with the use of incretin-based drugs in patients with type 2 diabetes mellitus.
Open accessAbstract
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.
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Metadata
- Authors
- Faillie, J.-L., Yu, O. H., Yin, H., Hillaire-Buys, D., Barkun, A., & Azoulay, L.
- Affiliations
- Université de Montpellier (FR)
- Jewish General Hospital (CA)
- Department of Medical Pharmacology and Toxicology, Montpellier University Hospital, Montpellier, France5Institut National de la Santé et de la Récherche Médicale (INSERM), Unité 1058, Faculty of Medicine, University Montpellier 1, Montpellier, France
- McGill University Health Centre (CA)
- Corresponding author
- Azoulay, Laurent
- Venue
- JAMA Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2016-10-01
- Volume
- 176
- Issue
- 10
- Pages
- 1474
- ISSN
- 2168-6106 (ISSN-L)
- OpenAlex
- W2485875310
- Cited by
- 134
- References
- 26
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 21 · 2023: 10 · 2022: 23 · 2021: 10 · 2020: 9 · 2019: 10 · 2018: 10 · 2017: 5 · 2016: 5
- FWCI
- 10.07
- Type
- journal article
- Language
- en
- Open access
- green
- hal.science
- Licence
- other-oa
- Locations
- JAMA Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Gastroenterology › Gallbladder and Bile Duct Disorders
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Keywords
- gallbladder disease, type 2 diabetes, DPP-4 inhibitors, GLP-1 receptor agonists, gallstones, cholecystitis, cholangitis, drug safety, antidiabetic drugs, hospitalization risk, oral antidiabetic drugs, drug-drug interactions, adverse drug reactions
- MeSH terms
- Adult, Bile Duct Diseases, Cholecystectomy, Diabetes Mellitus, Type 2, Female, Gallbladder Diseases, United Kingdom, Humans, Hypoglycemic Agents, Male, Cohort Studies, Incidence, Proportional Hazards Models, Glucagon-Like Peptide 1, Dipeptidyl-Peptidase IV Inhibitors
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