Association between glucagon‐like peptide‐1 receptor agonists and biliary‐related diseases in patients with type 2 diabetes: A nationwide cohort study
Abstract
Study Objective: Clinical trials have suggested that glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) may be associated with a higher risk of biliary‐related diseases in patients with type 2 diabetes. Limited real‐world studies have examined the comparative biliary safety of GLP‐1RAs versus other antihyperglycemic drugs. We aimed to estimate the comparative risk of biliary‐related diseases between GLP‐1RAs and sodium glucose cotransporter 2 inhibitors (SGLT2is), which are indicated for patients with similar diabetes severity in Taiwan. Design: Retrospective cohort study. Data Source: Taiwan National Health Insurance Database during 2011 to 2018. Patients: Patients with type 2 diabetes who initiated GLP‐1RAs or SGLT2is. Intervention: GLP‐1RAs versus SGLT2is. Measurements and Main Results: We used an on‐treatment approach to examine the effect of continuous use and an intention‐to‐treat approach to assess the effect of initiation of GLP‐1RAs versus SGLT2is. We used Coxregression models to estimate the hazard ratios (HRs) and 95% confidenceintervals (CIs) for the composite hospitalized biliary‐related diseases, including acute cholecystitis or cholecystectomy, choledocholithiasis, and acute cholangitis, after matching each GLP‐1RA initiator to up to 10 SGLT2iinitiators using propensity scores (PSs). Among 78,253 PS‐matched patients, GLP‐1RA use was associated with a numerically higher risk of biliary‐related diseases versus SGLT2i use in the on‐treatment analysis, with an HR of 1.20 (95% CI, 0.93–1.56) for the composite outcome, an HR of 1.22 (95% CI, 0.92–1.62) for acute cholecystitis or cholecystectomy, an HR of 1.20 (95% CI, 0.69–2.07) for choledocholithiasis, and an HR of 1.14 (95% CI,0.82–2.42) for acute cholangitis. The HRs were more pronounced in theintention‐to‐treat analysis (1.27 [95% CI, 1.05–1.53] for the composite outcome, 1.29 [95% CI, 1.04–1.58] foracute cholecystitis or cholecystectomy, 1.74 [95% CI, 1.23–2.46] for choledocholithiasis, and 1.31 [95% CI, 0.89–1.94] for acute cholangitis). The increased risk of the composite outcome associated with GLP‐1RAs was more evident in patients aged 〉60 years, women, and 120 days after treatment initiation. Liraglutide, but not dulaglutide, was associated with an elevated risk. Conclusions: GLP‐1RAs might be associated with an elevated risk of biliary‐related diseases compared to SGLT2is in Asian patients with type 2 diabetes.
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In the Taiwan study, liraglutide (HR 1.33; 95% CI 1.00 to 1.77) exhibited a significantly elevated risk of biliary-related diseases, whereas dulaglutide did not.
“In that study, liraglutide (HR, 1.33; 95% CI, 1.00 to 1.77) exhibited a significantly elevated risk, whereas dulaglutide did not.”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [36]
Real-world data from the Taiwan National Health Insurance Database documented an elevated risk of biliary-related diseases linked to GLP-1 RAs compared with SGLT-2 inhibitors.
“Extending the findings from the UK cohort study, additional real-world data derived from the Taiwan National Health Insurance Database—which encompasses Asian populations characterized by lower gallstone prevalence, low-fat and high-fiber dietary patterns, and lower body mass index—also documented an elevated risk of biliary-related diseases linked to GLP-1 RAs compared with SGLT-2 inhibitors [36]”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [36]
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- Authors
- Dong, Y., Wu, J., Chang, C., Lin, J., Wu, L., & Toh, S.
- Affiliations
- National Yang Ming Chiao Tung University (TW)
- University of California San Diego (US)
- National Taiwan University (TW)
- National Taiwan University Hospital (TW)
- Harvard University (US)
- Corresponding author
- Dong, Yaa‐Hui
- Chang, Chia‐Hsuin
- Venue
- Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
- Publisher
- Wiley
- Published
- 2022-05-17
- Volume
- 42
- Issue
- 6
- Pages
- 483-494
- ISSN
- 0277-0008 (ISSN-L)
- 1875-9114
- OpenAlex
- W4229012390
- Cited by
- 16
- References
- 37
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 2 · 2022: 1
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology, Taiwan (MOST 109‐2314‐B‐002‐153‐MY2)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gallbladder and Bile Duct Disorders
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- GLP-1 receptor agonists, SGLT2 inhibitors, type 2 diabetes, acute cholecystitis, cholecystectomy, choledocholithiasis, acute cholangitis, drug safety, comparative risk, propensity score matching, Taiwan National Health Insurance Research Database, antidiabetic drugs
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, Cholangitis, Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Retrospective Studies, Cohort Studies, Cholecystitis, Acute, Choledocholithiasis
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