Risk of Hepatocellular Carcinoma with Glucagon-like Peptide-1 receptor agonist treatment in patients: a systematic review and meta-analysis

Nov 17, 2024BMC endocrine disorders

Risk of Liver Cancer with Glucagon-like Peptide-1 Receptor Agonist Treatment in Patients: A Systematic Review and Meta-Analysis

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Abstract

GLP-1 receptor agonist treatment was associated with a significant reduction in hepatocellular carcinoma risk (pooled HR = 0.41) compared to insulin or no GLP-1 RA treatment.

Eight studies were included in the analysis, focusing on T2DM patients treated with GLP-1 receptor agonists.
GLP-1 RAs demonstrated a significant reduction in HCC risk when compared to insulin or no treatment.
No significant differences in HCC risk were observed when comparing GLP-1 RAs to metformin or DPP-4 inhibitors.
A reduced risk of HCC was noted when comparing GLP-1 RAs to sulfonylureas.
Considerable heterogeneity was present in the results, indicating variability among the included studies.

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BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide, with increased prevalence in individuals with chronic liver conditions and type 2 diabetes mellitus (T2DM). Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) have shown promise in diabetes management and may influence liver disease progression. This systematic review and meta-analysis aimed to assess the efficacy of GLP-1 RAs in reducing the risk of HCC in patients with T2DM.

METHODS: We conducted a literature search of PubMed, EMBASE, and Web of Science up to August 1, 2024. Studies that evaluated the incidence of HCC in T2DM patients treated with GLP-1 RAs compared to other therapies were included. Meta-analyses were performed using a random-effects model to compute pooled hazard ratios (HRs) and 95% confidence intervals (CIs), and heterogeneity was assessed using the I² statistic. All statistical analyses were performed in R software version 4.3.

RESULTS: Eight studies met the inclusion criteria. The pooled analysis demonstrated that GLP-1 RA treatment was associated with a significant reduction in HCC risk compared to insulin or no GLP-1 RA treatment (pooled HR = 0.41, 95% CI: 0.28 to 0.55), with considerable heterogeneity (I² = 74%). Compared to metformin and DPP-4 inhibitors, GLP-1 RAs did not significantly alter HCC risk (HR = 0.99, 95% CI: 0.79 to 1.27 for metformin; HR = 1.05, 95% CI: 0.80 to 1.39 for DPP-4 inhibitors). However, GLP-1 RAs were associated with a reduced risk compared to sulfonylureas (HR = 0.78, 95% CI: 0.65 to 0.93).

CONCLUSION: GLP-1 RAs may offer protective benefits against HCC in T2DM patients compared to insulin or no GLP-1 RAs, but not significantly over other antidiabetic medications. This review indicates the need for further randomized controlled trials to clarify the role of GLP-1 RAs in HCC risk mitigation and to explore their mechanistic pathways in liver disease management.

Key numbers

0.41

for Risk Reduction

Pooled from 8 studies comparing treatment to insulin or no .

0.99

Comparing GLP-1 RAs to Metformin

from studies comparing GLP-1 RAs to metformin treatment.

0.78

Comparing GLP-1 RAs to Sulfonylureas

from studies comparing GLP-1 RAs to sulfonylureas.

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Risk of Hepatocellular Carcinoma with Glucagon-like Peptide-1 receptor agonist treatment in patients: a systematic review and meta-analysis

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