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^{1

2

3}, Jo-Hsuan Wu⁴, Chia-Hsuin Chang^{5

6

7}, Jou-Wei Lin^{5

8

9}, Li-Chiu Wu⁵, Sengwee Toh¹⁰

Affiliations

¹ Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
² Institute of Public Health, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
³ Institute of Hospital and Health Care Administration, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁴ Shiley Eye Institute and Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center, University of California, San Diego, California, USA.
⁵ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁶ Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁷ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
⁸ Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Douliou City, Taiwan.
⁹ Cardiovascular Center, National Taiwan University Hospital Yunlin Branch, Douliou City, Taiwan.
¹⁰ Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA.

PMID: 35508702
DOI: 10.1002/phar.2688

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 et al. Pharmacotherapy. 2022 Jun.

. 2022 Jun;42(6):483-494.

doi: 10.1002/phar.2688. Epub 2022 May 17.

Authors

Yaa-Hui Dong^{1

2

3}, Jo-Hsuan Wu⁴, Chia-Hsuin Chang^{5

6

7}, Jou-Wei Lin^{5

8

9}, Li-Chiu Wu⁵, Sengwee Toh¹⁰

Affiliations

¹ Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
² Institute of Public Health, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
³ Institute of Hospital and Health Care Administration, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁴ Shiley Eye Institute and Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center, University of California, San Diego, California, USA.
⁵ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁶ Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁷ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
⁸ Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Douliou City, Taiwan.
⁹ Cardiovascular Center, National Taiwan University Hospital Yunlin Branch, Douliou City, Taiwan.
¹⁰ Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA.

PMID: 35508702
DOI: 10.1002/phar.2688

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.

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

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

Authors

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Abstract

References

REFERENCES

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Full Text Sources

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Medical