Metformin, cancer and glucose metabolism

    1. Davide Maggi1,2
    1. 1Department of Internal Medicine (DIMI), University of Genova, Viale Benedetto XV/6, 16132 Genova, Italy
      2IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy
      3Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Alma Mater Studiorum, University of Bologna, Bologna, Italy
      4CNR Institute of Organic Synthesis and Photoreactivity (ISOF), 40129 Bologna, Italy
      5CNR Institute of Molecular Bioimaging and Physiology (IBFM), 16132 Genova, Italy
      6Department of Health Science (DISSAL), University of Genova, 16132 Genova, Italy
    1. Correspondence should be addressed to D Maggi; Email: davide.maggi{at}


    Metformin is the first-line treatment for type 2 diabetes. Results from several clinical studies have indicated that type 2 diabetic patients treated with metformin might have a lower cancer risk. One of the primary metabolic changes observed in malignant cell transformation is an increased catabolic glucose metabolism. In this context, once it has entered the cell through organic cation transporters, metformin decreases mitochondrial respiration chain activity and ATP production that, in turn, activates AMP-activated protein kinase, which regulates energy homeostasis. In addition, metformin reduces cellular energy availability and glucose entrapment by inhibiting hexokinase-II, which catalyses the glucose phosphorylation reaction. In this review, we discuss recent findings on molecular mechanisms that sustain the anticancer effect of metformin through regulation of glucose metabolism. In particular, we have focused on the emerging action of metformin on glycolysis in normal and cancer cells, with a drug discovery perspective.

    • Received 26 September 2014
    • Accepted 1 October 2014
    • Made available online as an Accepted Preprint 1 October 2014
    | Table of Contents

    This Article

    1. Endocr Relat Cancer 21 R461-R471
    1. Abstract
    2. Figures Only
    3. Supplementary Figure
    4. All Versions of this Article:
      1. ERC-14-0284v1
      2. 21/6/R461 most recent