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Meta-Analysis
. 2024 Nov 18;24(1):246.
doi: 10.1186/s12902-024-01775-2.

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

Muhammed Shabil #  1   2 , Mahalaqua Nazli Khatib #  3 , Suhas Ballal  4 , Pooja Bansal  5 , Balvir S Tomar  6 , Ayash Ashraf  7 , M Ravi Kumar  8 , Aashna Sinha  9 , Pramod Rawat  10   11 , Abhay M Gaidhane  12 , Sanjit Sah  13   14 , Afukonyo Shidoiku Daniel  15 , Ambanna Yappalparvi  16 , Ganesh Bushi  17
Affiliations
Meta-Analysis

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

Muhammed Shabil et al. BMC Endocr Disord. .

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.

Keywords: Glucagon-like Peptide-1 receptor agonists; Hepatocellular carcinoma; Meta-analysis; Type 2 diabetes mellitus.

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Conflict of interest statement

Declarations Ethical approval Not required. Consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flowchart showing article screening and selection process
Fig. 2
Fig. 2
Forest plot showing pooled HRs for HCC risk with GLP-1 RA vs. no GLP-1 RA or insulin
Fig. 3
Fig. 3
Subgroup analysis showing pooled HRs for HCC risk with GLP-1 RA vs. no GLP-1 RA and insulin comparators
Fig. 4
Fig. 4
Sensitivity analysis showing pooled HRs for HCC risk, including only studies with participants without liver disease
Fig. 5
Fig. 5
Doi plot assessing publication bias
See this image and copyright information in PMC

References

    1. Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Reviews Gastroenterol Hepatol. 2021;18(4):223–38. - PMC - PubMed
    1. Crane H, Eslick GD, Gofton C, Shaikh A, Cholankeril G, Cheah M, et al. Global prevalence of metabolic dysfunction-associated fatty liver disease-related hepatocellular carcinoma: a systematic review and meta-analysis. Clin Mol Hepatol. 2024;30(3):436. - PMC - PubMed
    1. Ajmera V, Cepin S, Tesfai K, Hofflich H, Cadman K, Lopez S, et al. A prospective study on the prevalence of NAFLD, advanced fibrosis, cirrhosis and hepatocellular carcinoma in people with type 2 diabetes. J Hepatol. 2023;78(3):471–8. - PMC - PubMed
    1. Doycheva I, Zhang T, Amjad W, Thuluvath PJ. Diabetes and hepatocellular carcinoma: incidence trends and impact of liver disease etiology. J Clin Experimental Hepatol. 2020;10(4):296–303. - PMC - PubMed
    1. Morrison L, Gabison J, Oshman L. GLP-1 RAs and SGLT2-Is to lower glucose and reduce the risk of Cardiovascular and Diabetic kidney disease. J Am Board Family Med. 2024;37(3):372–82. - PubMed

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