Effects of metformin on clinical outcome in diabetic patients with advanced HCC receiving sorafenib

Andrea Casadei Gardini, Giorgia Marisi, Emanuela Scarpi, Mario Scartozzi, Luca Faloppi, Nicola Silvestris, Gianluca Masi, Caterina Vivaldi, Oronzo Brunetti, Stefano Tamberi, Francesco Giuseppe Foschi, Emiliano Tamburini, Elena Tenti, Salvatore Ricca Rosellini, Paola Ulivi, Stefano Cascinu, Oriana Nanni, Giovanni Luca Frassineti

Research output: Contribution to journalArticlepeer-review


Background and objective: Several studies have reported an association between type 2 diabetes mellitus and hepatocellular carcinoma (HCC). Data from several retrospective studies and meta-analyses have highlighted a reduction of about 50% in the risk of developing HCC in cirrhotic patients treated with metformin for diabetes. The aim of this study was to evaluate the different outcomes of patients who received or did not receive metformin during treatment with sorafenib.Methods: We analyzed 93 patients consecutively treated with sorafenib. Forty-two (45.2%) patients were diabetic, of whom 31 were on metformin. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared with the log-rank test.Results: The concomitant use of sorafenib and metformin was associated with a median PFS of 2.6 months (95% CI 1.9-3.3) compared to 5.0 months (95% CI 2.5-8.2) for patients receiving sorafenib alone (p = 0.029). The median OS of patients treated with the combination was 10.4 months (95% CI 3.9-14.4) compared to 15.1 months (95% CI 11.7-17.8) for those who were not given metformin (p = 0.014).Conclusions: Our findings could be the result of increased tumor aggressiveness and resistance to sorafenib in metformin-treated patients.

Original languageEnglish
Pages (from-to)2719-2725
Number of pages7
JournalExpert Opinion on Pharmacotherapy
Issue number18
Publication statusPublished - Dec 12 2015


  • diabetes
  • hepatocellular carcinoma
  • insulin
  • metformin
  • sorafenib

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology


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