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

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

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

BMC Endocr Disord. 2024 Nov 18;24(1):246. doi: 10.1186/s12902-024-01775-2.

Authors

Muhammed Shabil^#^{1

2}, Mahalaqua Nazli Khatib^#³, Suhas Ballal⁴, Pooja Bansal⁵, Balvir S Tomar⁶, Ayash Ashraf⁷, M Ravi Kumar⁸, Aashna Sinha⁹, Pramod Rawat^{10

11}, Abhay M Gaidhane¹², Sanjit Sah^{13

14}, Afukonyo Shidoiku Daniel¹⁵, Ambanna Yappalparvi¹⁶, Ganesh Bushi¹⁷

Affiliations

¹ University Center for Research and Development, Chandigarh University, Mohali, Punjab, India.
² Medical Laboratories Techniques Department, AL-Mustaqbal University, Hillah, Babil, 51001, Iraq.
³ Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, City: Wardha, India.
⁴ Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India.
⁵ Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan, 303012, India.
⁶ Institute of Pediatric Gastroenterology and Hepatology, NIMS University, Jaipur, India.
⁷ Chandigarh Pharmacy College, Chandigarh Group of College, City: Jhanjeri, Mohali, 140307, Punjab, India.
⁸ Department of Chemistry, Raghu Engineering College, Visakhapatnam, 531162, Andhra Pradesh, India.
⁹ School of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, India.
¹⁰ Department of Biotechnology, Graphic Era (Deemed to be University, Dehradun, 248002, India.
¹¹ Department of Allied Sciences, Graphic Era Hill University Clement Town, City: Dehradun, 248002, India.
¹² Global Health Academy, School of Epidemiology and Public Health, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education, City: Wardha, India. abhay.psm@dmiher.edu.in.
¹³ Department of Paediatrics, Hospital and Research Centre, Dr. D. Y. Patil Medical College, Dr. D. Y. Patil Vidyapeeth, Pune, 411018, Maharashtra, India.
¹⁴ Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth, Pune, 411018, Maharashtra, India.
¹⁵ Global Health and Infectious Diseases Control Institute, Nasarawa State University, Keffi, Nigeria. afukonyoshidoiku@tsuniversity.edu.ng.
¹⁶ School of Pharmaceutical Sciences, 16 Lovely Professional University, Phagwara, India.
¹⁷ Center for Global Health Research, Saveetha Institute of Medical and Technical Sciences, Saveetha Medical College and Hospital, Saveetha University, Chennai, India.

^# Contributed equally.

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.

Publication types

Systematic Review
Meta-Analysis

MeSH terms

Carcinoma, Hepatocellular*
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / drug therapy
Glucagon-Like Peptide-1 Receptor* / agonists
Humans
Hypoglycemic Agents* / therapeutic use
Liver Neoplasms* / epidemiology

Substances

Glucagon-Like Peptide-1 Receptor
Hypoglycemic Agents