Association of glucagon-like peptide-1 receptor agonists with serious liver events among patients with type 2 diabetes: A scandinavian cohort study.

BACKGROUND AND AIMS: Clinical trials suggest that glucagon-like peptide-1 (GLP-1) receptor agonists may have beneficial effects on NAFLD but the impact on hard hepatic endpoints is unknown. We assessed the association between use of GLP-1 receptor agonists and risk of serious liver events in routine clinical practice.

APPROACH AND RESULTS: Cohort study using data from nationwide registers in Sweden, Denmark and Norway, 2007-2020, including 91 479 initiators of GLP-1 receptor agonists and 244 004 initiators of the active comparator, dipeptidyl peptidase-4 (DPP4) inhibitors, without a history of chronic liver disease other than NAFLD/NASH. The primary outcome was serious liver events: a composite of incident compensated and decompensated cirrhosis and hepatocellular carcinoma. Secondary outcomes were the individual components of the primary outcome. Cox regression was used to estimate hazard ratios (HRs), using propensity score weighting to control for confounding. Users of GLP-1 receptor agonists had 608 serious liver events (adjusted incidence rate 16.9 events per 10 000 person-years), compared with 1770 events among users of DPP4 inhibitors (19.2 events per 10 000 person-years). The adjusted HR was 0.85 (95% CI 0.75 to 0.97) and the rate difference was -2.1 (-4.4 to 0.1) events per 10 000 person-years. In secondary outcome analyses the adjusted HR was 0.85 (0.75 to 0.97) for compensated and decompensated cirrhosis and 1.05 (0.80 to 1.39) for hepatocellular carcinoma.

CONCLUSIONS: Use of GLP-1 receptor agonists was associated with a significantly reduced risk of serious liver events, driven by a reduction of compensated and decompensated cirrhosis.