| Summary: | Introduction: This study aimed to compare the therapeutic efficacy of metformin and other anti-hyperglycemic agents in hepatocellular carcinoma (HCC) patients with type 2 diabetes (T2D). Materials: A systematic electronic search on keywords including HCC and different anti-hyperglycemic agents was performed through electronic databases including Medline and EMBASE. The primary outcome was the overall survival (OS). The secondary outcomes were the recurrence-free survival (RFS) and progression-free survival (PFS). Results: Six retrospective cohort studies were included for analysis: Four studies with curative treatment for HCC (618 patients with metformin and 532 patients with other anti-hyperglycemic agents) and two studies with non-curative treatment for HCC (92 patients with metformin and 57 patients with other anti-hyperglycemic agents). Treatment with metformin was associated with significantly longer OS (OR1 yr = 2.62, 95%CI: 1.76–3.90; OR3 yr = 3.14, 95%CI: 2.33–4.24; OR5 yr = 3.31, 95%CI: 2.39–4.59, all P < 0.00001) and RFS (OR1 yr = 2.52, 95%CI: 1.84–3.44; OR3 yr = 2.87, 95%CI: 2.15–3.84; all P < 0.00001; and OR5 yr = 2.26, 95%CI: 0.94–5.45, P = 0.07) rates vs. those of other anti-hyperglycemic agents after curative therapies for HCC. However, both of the two studies reported that following non-curative HCC treatment, there were no significant differences in the OS and PFS rates between the metformin and non-metformin groups (I2 > 50%). Conclusions: Metformin significantly prolonged the survival of HCC patients with T2D after the curative treatment of HCC. However, the efficacy of metformin needs to be further determined after non-curative therapies for HCC patients with T2D.
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