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

Expert Opin Pharmacother. 2015;16(18):2719-25. doi: 10.1517/14656566.2015.1102887. Epub 2015 Oct 29.

Abstract

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.

Keywords: diabetes; hepatocellular carcinoma; insulin; metformin; sorafenib.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / drug therapy*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Resistance, Neoplasm
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Liver Neoplasms / complications
  • Liver Neoplasms / drug therapy*
  • Metformin / therapeutic use*
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*
  • Retrospective Studies
  • Sorafenib
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Hypoglycemic Agents
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Niacinamide
  • Metformin
  • Sorafenib