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Open Access 01-12-2024 | Hepatocellular Carcinoma | Systematic Review

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

Authors: Muhammed Shabil, Mahalaqua Nazli Khatib, Suhas Ballal, Pooja Bansal, Balvir S. Tomar, Ayash Ashraf, M. Ravi Kumar, Aashna Sinha, Pramod Rawat, Abhay M. Gaidhane, Sanjit Sah, Afukonyo Shidoiku Daniel, Ambanna Yappalparvi, Ganesh Bushi

Published in: BMC Endocrine Disorders | Issue 1/2024

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Abstract

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.
Appendix
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Metadata
Title
Risk of Hepatocellular Carcinoma with Glucagon-like Peptide-1 receptor agonist treatment in patients: a systematic review and meta-analysis
Authors
Muhammed Shabil
Mahalaqua Nazli Khatib
Suhas Ballal
Pooja Bansal
Balvir S. Tomar
Ayash Ashraf
M. Ravi Kumar
Aashna Sinha
Pramod Rawat
Abhay M. Gaidhane
Sanjit Sah
Afukonyo Shidoiku Daniel
Ambanna Yappalparvi
Ganesh Bushi
Publication date
01-12-2024

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