Published online Aug 15, 2023. doi: 10.4239/wjd.v14.i8.1289
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
Processing time: 164 Days and 15.3 Hours
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.
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.
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).
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.
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).
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.
Further large studies are required to definitively clarify the real impact of metformin as a chemopreventive agent for HCC.