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

Dec 12, 2023Hepatology (Baltimore, Md.)

Glucagon-like peptide-1 drugs linked to serious liver problems in people with type 2 diabetes: A Scandinavian study

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Abstract

Users of GLP-1 receptor agonists experienced 608 serious liver events compared to 1770 events among users of DPP-4 inhibitors.

The adjusted incidence rate of serious liver events was 16.9 events per 10,000 person-years for GLP-1 receptor agonist users.
In contrast, the incidence rate for DPP-4 inhibitor users was 19.2 events per 10,000 person-years.
The adjusted hazard ratio for serious liver events in GLP-1 receptor agonist users was 0.85, indicating a potential reduction in risk.
The rate difference for serious liver events between the two groups was -2.1 events per 10,000 person-years.
For compensated and decompensated cirrhosis, the adjusted hazard ratio was 0.85, suggesting a lower risk with GLP-1 receptor agonists.
The hazard ratio for hepatocellular carcinoma (HCC) was 1.05, indicating no significant difference in risk.

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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 end points is unknown. We assessed the association between the use of GLP-1 receptor agonists and the 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 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 HCC. Secondary outcomes were the individual components of the primary outcome. Cox regression was used to estimate 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 dipeptidyl peptidase-4 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 HCC.

CONCLUSIONS: The 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.

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

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