Metformin use improves survival of diabetic liver cancer patients: systematic review and meta-analysis

Shu-Juan Ma, Yi-Xiang Zheng, Peng-Cheng Zhou, Yan-Ni Xiao and Hong-Zhuan Tan _

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Oncotarget. 2016; 7:66202-66211. https://doi.org/10.18632/oncotarget.11033

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Shu-Juan Ma1, Yi-Xiang Zheng2, Peng-Cheng Zhou2, Yan-Ni Xiao1 and Hong-Zhuan Tan1

1 Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China

2 Department of Infectious Disease, Viral Hepatitis Key Laboratory of Hunan Province, Xiangya Hospital, Central South University, Changsha, China

Correspondence to:

Hong-Zhuan Tan, email:

Keywords: metformin, liver cancer, survival, diabetes mellitus, meta-analysis

Received: May 22, 2016 Accepted: July 19, 2016 Published: August 02, 2016


Metformin has garnered considerable interest as a chemo-preventive and chemo-therapeutic agent given the increased risk of liver cancer among diabetic patients. This work was performed to illustrate the association between metformin use and survival of diabetic liver cancer patients. We conducted a comprehensive literature search of PubMed, Web of Science, Embase, BIOSIS Previews, Cochrane Library from inception to 12 May 2016. Meta-analyses were performed using Stata (version 12.0), with hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) as effect measures. Eleven cohort studies involving 3452 liver cancer patients fulfilled the inclusion criteria. Meta-analyses showed that metformin use was associated with better survival (HR = 0.59; 95% CI, 0.42-0.83; p = 0.002) of liver cancer patients, and the beneficial effect persisted (HR = 0.64; 95% CI, 0.42-0.97; p = 0.035) when the population was restricted to diabetic liver cancer patients. After adjusting for age, etiology, index of tumor severity and treatment of liver cancer, the association between metformin use and better survival of liver cancer patients was stable, pooled HR ranged from 0.47 to 0.57. The results indicated that metformin use improved survival of diabetic liver cancer patients. However, the results should be interpreted with caution given the possibility of residual confounding. Further prospective studies are still needed to confirm the prognostic benefit of metformin use.

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