Meta-Analysis
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 15, 2023; 14(8): 1289-1300
Published online Aug 15, 2023. doi: 10.4239/wjd.v14.i8.1289
Prognostic role of metformin in diabetes mellitus type 2 patients with hepatocellular carcinoma: A systematic review and meta-analysis
Maja Cigrovski Berkovic, Francesco Giovanardi, Anna Mrzljak, Quirino Lai
Maja Cigrovski Berkovic, Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb, Zagreb 10000, Croatia
Francesco Giovanardi, Quirino Lai, General Surgery and Organ Transplantation Unit, Department of Surgery, Sapienza University of Rome, Rome 00018, Italy
Anna Mrzljak, Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb 10000, Croatia
Anna Mrzljak, Department of Medicine, School of Medicine, Zagreb 10000, Croatia
Author contributions: Lai Q and Mrzljak A contributed to the conception and design of the study; Giovanardi F and Lai Q contributed to the acquisition of data; Lai Q and Giovanardi F analyzed and interpreted the data; Mrzljak A and Cigovski Berkovic M drafted the article; Lai Q critically revised the manuscript; and all authors approved the final version.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Maja Cigrovski Berkovic, MD, PhD, Adjunct Associate Professor, Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb, Horvaćanski zavoj 15, Zagreb 10000, Croatia. maja.cigrovskiberkovic@gmail.com
Received: February 27, 2023
Peer-review started: February 27, 2023
First decision: April 11, 2023
Revised: April 24, 2023
Accepted: May 16, 2023
Article in press: May 16, 2023
Published online: August 15, 2023
ARTICLE HIGHLIGHTS
Research background

Hepatocellular carcinoma (HCC) is a common malignancy associated with significant cancer-related death. Therefore, it is important to identify chemopreventive potential to lower the risk of an HCC adverse course. Metformin has been associated with a lower risk of HCC development, but its role in prevention of death, tumor progression, and recurrence after any HCC treatment in type 2 diabetes mellitus (T2DM) patients is still inconclusive.

Research motivation

Metformin is a first-line therapeutic option for T2DM, with expanded re-purposing in the treatment of different cancer types. Whether it can improve long-term outcomes in the HCC setting is still unclear. Therefore, we performed a systematic review and meta-analysis to further explore its chemopreventive role in HCC patients.

Research objectives

We focused on the role of metformin in patients with T2DM and HCC in terms of outcomes (death, or progressive disease, or recurrence) receiving any tumor therapy. Moreover, we performed subgroup analyses (including different types of HCC treatment and different ethnicities).

Research methods

We performed a systematic review via a search of PubMed and Cochrane Central Register of Controlled Trials Databases of the published literature focused on the role of metformin in patients with T2DM and HCC receiving any tumor therapy.

Research results

We included 13 studies (n = 14886 patients) in this review. A decreased risk was reported in cases receiving metformin, although this value did not reach statistical significance [odds ratio (OR) = 0.89, P = 0.42]. When only patients treated with curative strategies were considered, a more marked correlation between metformin and favorable cases was reported (OR = 0.70, P = 0.068). In the case of a palliative treatment, there was no correlation between metformin and favorable cases (OR = 0.74, P = 0.66). With regard to the risk of progressive disease and recurrence, no obvious correlation between metformin use and reduced risk was reported. Moreover, there was a tendency for a decreased risk of death with metformin use in patients from Eastern countries (OR = 0.69, P = 0.17), but the same was not seen in patients from Western countries (OR = 1.19; P = 0.31).

Research conclusions

Metformin failed to have a relevant impact on preventing adverse effects after HCC treatment. A trend was reported in T2DM cases receiving curative therapies in relation to the risk of death.

Research perspectives

Further large studies are required to definitively clarify the real impact of metformin as a chemopreventive agent for HCC.