Meta-analysis: The efficacy of metformin and other anti-hyperglycemic agents in prolonging the survival of hepatocellular carcinoma patients with type 2 diabetes.

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 (OR=2.62, 95%CI: 1.76-3.90; OR=3.14, 95%CI: 2.33-4.24; OR=3.31, 95%CI: 2.39-4.59, all P<0.00001) and RFS (OR=2.52, 95%CI: 1.84-3.44; OR=2.87, 95%CI: 2.15-3.84; all P<0.00001; and OR=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 (I>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.