Glucagon-like peptide-1 receptor agonist use is associated with a lower risk of major adverse liver-related outcomes: a meta-analysis of observational cohort studies

Feb 27, 2025Gut

Use of glucagon-like peptide-1 receptor activators is linked to lower risk of serious liver problems

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Abstract

GLP-1 receptor agonists (GLP-1RAs) are associated with a 71% lower risk of major adverse liver-related outcomes (MALOs) in individuals with type 2 diabetes.

Analysis included 11 cohort studies with data from 1,467,220 patients with type 2 diabetes.
GLP-1RA use is linked to a reduced risk of hepatic decompensation, with an incidence rate ratio (IRR) of 0.70.
There is a noted association with a reduced risk of hepatocellular carcinoma (HCC), although this was less definitive (IRR 0.82).
GLP-1RAs demonstrated greater effectiveness compared to other glucose-lowering medications in preventing MALOs and hepatic decompensation.
Compared to insulin therapy, GLP-1RAs showed a significantly lower risk of developing HCC (IRR 0.32).

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BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promising effects on liver histology in phase 2 trials enrolling patients with metabolic dysfunction-associated steatotic liver disease. However, the impact of GLP-1RAs on the long-term risk of major adverse liver-related outcomes (MALOs) remains uncertain.

OBJECTIVE: We performed a meta-analysis of observational cohort studies to quantify the magnitude and direction of the association between GLP-1RA use and MALOs in people with type 2 diabetes (T2D).

DESIGN: We systematically searched eligible cohort studies comparing GLP-1RA new users versus users of other glucose-lowering medications. The primary outcome was the cumulative incidence rates of MALOs. Secondary outcomes included hepatic decompensation events, hepatocellular carcinoma (HCC) and liver-related mortality. Random-effects models were used to calculate incidence rate ratios (IRRs).

RESULTS: 11 retrospective cohort studies with aggregate data on 1 467 220 patients with T2D (647 903 GLP-1RA new users, 819 317 non-users) were included. GLP-1RA use was significantly associated with a lower risk of MALOs (IRR 0.71, 95% CI 0.57 to 0.88) and hepatic decompensation (IRR 0.70, 95% CI 0.52 to 0.94). Association with reduced risk of HCC was also observed (IRR 0.82, 95% CI 0.61 to 1.11). Compared with other antidiabetic medications, GLP-1RAs showed superior effectiveness versus SGLT2 inhibitors in preventing MALOs (IRR 0.93, 95% CI 0.87 to 0.99), versus DPP-4 inhibitors in preventing hepatic decompensation (IRR 0.74, 95% CI 0.66 to 0.83) and versus insulin therapy in preventing HCC (IRR 0.32, 95% CI 0.13 to 0.80).

CONCLUSIONS: GLP-1RA use is associated with a lower risk of liver-related complications and hepatic decompensation in people with T2D. These findings suggest a role of GLP-1RAs in preventing liver-related complications beyond their beneficial cardiometabolic effects.

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Glucagon-like peptide-1 receptor agonist use is associated with a lower risk of major adverse liver-related outcomes: a meta-analysis of observational cohort studies

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