Association between glucagon-like peptide-1 receptor agonists and biliary-related diseases in patients with type 2 diabetes: A nationwide cohort study

Yaa Hui Dong*, Jo Hsuan Wu, Chia Hsuin Chang, Jou Wei Lin, Li Chiu Wu, Sengwee Toh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Pages (from-to)483-494
Number of pages12
JournalPharmacotherapy
Volume42
Issue number6
DOIs
StatePublished - Jun 2022

Keywords

  • acute cholangitis
  • acute cholecystitis
  • biliary-related diseases
  • cholecystectomy
  • choledocholithiasis
  • cohort study
  • glucagon-like peptide-1 receptor agonists
  • pharmacoepidemiology
  • sodium glucose cotransporter 2 inhibitors
  • type 2 diabetes

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