Effect of metformin on hepatocellular carcinoma patients with type II diabetes receiving transarterial chemoembolization: a multicenter retrospective cohort study.

ABSTRACT

BACKGROUND: Diabetes is prevalent among patients with hepatocellular carcinoma (HCC) and is associated with a poor prognosis. Although the hypoglycemic drug metformin has shown anti-tumor effects, its potential positive effect on patients with HCC and diabetes undergoing transarterial chemoembolization (TACE) remains unclear. Therefore, this study aimed to investigate the efficacy and safety of metformin in patients with HCC and type II diabetes who are receiving TACE. MATERIALS AND METHODS: This retrospective study involved 372 consecutive patients with HCC and type II diabetes across three medical centers between January 2014 and June 2021. All patients underwent TACE. Propensity score matching (PSM) was used to reduce selection bias. Cox proportional hazards regression was employed to compare all-cause death between the metformin and non-metformin groups, while competing risk regression was performed to assess cancer-specific death. RESULTS: Among 372 patients included in the study, 208 patients (177 male patients and 31 female patients) with mean age 59.6 (10.3) years received metformin and 164 patients (139 male patients and 25 female patients) with mean age 60.3 (10.0) years did not. Before PSM, patients with metformin had significantly longer median overall survival (mOS) and median progression-free survival (mPFS) than those without metformin (mOS 34 months, 95% CI 25.6-42.4 vs. 20 months, 95% CI 15.3-24.7; P<0.001; mPFS 11 months, 95% CI 9.3-12.7 vs. 8 months, 95% CI 5.9-10.1; P<0.001). Similar results were observed after PSM. Multivariate regression analysis indicated that metformin was associated with a reduced risk of all-cause mortality (HR 0.589, 95% CI 0.454-0.763; P<0.001) and tumor progression (HR 0.667, 95% CI 0.526-0.845; P=0.001) before PSM. After excluding deaths related to other factors, metformin continued to demonstrate a reduction in cancer-specific mortality risk among the patients. Subgroup analysis further revealed that patients using metformin had lower all-cause mortality risk and tumor progression risk than those without metformin in most subgroups. Adverse event evaluation suggested that metformin could lead to elevated nausea incidence. CONCLUSION: Metformin may confer survival benefits to patients with HCC and type II diabetes undergoing TACE. Metformin may simultaneously address multiple aspects of treatment in these patients.