Author information
1
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
2
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
3
Department of Internal Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
4
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover, Germany.
5
Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany.
Abstract
BACKGROUND:
Hepatocellular carcinoma (HCC) is one of the most lethal cancers. Nutrition- and life style-associated risk factors are increasingly prevalent. Metformin, the mainstay of type 2 diabetes mellitus (T2DM)-treatment, reduces the risk of hepatocarcinogenesis. However, its influence on the prognosis of patients with HCC has not been investigated on a large scale, yet.
METHODS:
5,093 patients treated for HCC between 2000-2016 at three referral centers were included in this retrospective multi-center study. The aim of this study was to assess whether treatment with metformin for T2DM is associated with a prolonged overall survival (OS) in patients diagnosed with HCC.
RESULTS:
Among 5,093 patients with HCC, 1,917 patients (37.6%) were diagnosed with T2DM, of which 338 (17.6%) received treatment with metformin. Compared to diabetic patients not treated with metformin, patients on metformin had a significantly better hepatic function (Child-Pugh-Score A: 69.2%vs.47.4%, p<0.001) and underwent significantly more often tumor resection (22.1%vs.16.5%, p=0.024). Patients on metformin had a significantly longer median OS (mOS) compared to diabetic patients not treated with metformin (22vs.15months, p=0.019). The prolongation of survival was most significant in patients treated with surgery. Using a propensity score match (PSM), patients were adjusted for hepatic function and initial therapy. In the matched cohorts, mOS remained significantly longer in metformin-treated patients (22vs.16months, p=0.021). Co-treatment of metformin and sorafenib was associated with a survival disadvantage.
CONCLUSION:
Treatment with metformin was associated with an improved survival in patients with T2DM and HCC. This effect was most pronounced in patients at potentially curative tumor stages.