Hepatocellular carcinoma (HCC) recurrence following hepatic resection (HR) and liver transplantation (LT) remains a great concern. We assessed the antitumor effects of metformin in patients treated with sorafenib for HCC recurrence after HR or LT.

The two clinical retrospective studies involved metformin therapy of 304 HR patients and 74 LT recipients who were treated with sorafenib.

In the study involving patients who had undergone HR, death occurred in 245 of the 304 patients (80.6%) during a median follow-up of 10.2 months after sorafenib administration. The metformin HR group (group 1; n=40) showed no prognostic difference in progression-free and overall survival rates compared with the all-HR control group (group 3; n=241) and propensity score-matched HR control group (group 4; n=80). In the clinical study of recipients exposed to LT, death occurred in 62 of the 74 patients (83.8%) during a median follow-up of 13.6 months (range: 3–76 months) after sorafenib administration. The metformin LT group (group 5; n=14) showed no prognostic difference in progression-free and overall survival rates compared with the all-LT control group (group 7; n=43) and propensity score-matched LT control group (group 8; n=28).

Our clinical studies demonstrated absence of synergistic antitumor effects of metformin. Further high-volume studies are necessary to assess the role of metformin in patients treated with sorafenib for advanced HCC.