Table I.

Summary of metformin molecular and metabolic actions

Anti-obesity effects: Decreased appetite Increased GLP-1 secretion

Anti-hyperglycemic effects: Decreased intestinal carbohydrate absorption (decreased postprandial hyperglycemia) Inhibition of hepatic gluconeogenesis: inhibition of the Krebs cycle and/or oxidative phosphorylation by activation of AMPK Enhancement of insulin-stimulated glucose transport in skeletal muscle: increased recruitment and activity of GLUT-4 and enhanced non-oxidative disposal into skeletal muscle

Anti-lipidemic effects: Increased free fatty acid esterification and inhibition of lipolysis in adipose tissue

Anti-diabetic protective effects: Protection of β-cells from glucose toxicity and lipotoxicity: protection of β-cell secretory capacity, prevention of acceleration to severe diabetes

Hepatoprotective effects: Decreased hepatic insulin resistance and improved lipemia levels

Anti-neoplastic effects: Indirect effect: via decreased insulin resistance and decreased IGF-1 levels Direct effect: via AMPK-related and AMPK-independentcellular pathways

Cardioprotective effects: Cumulative effects of decreased weight gain and better lipid profile provided by long-term use Undefined serologic or endothelial factors such as PAI-1

GLP-1 – glucagon-like peptide-1, AMPK – AMP-activated protein kinase, GLUT-4 – glucose transporter type 4, IGF-1 – insulin-like growth factor 1, PAI-1 – plasminogen activator inhibitor-1