Metformin and its clinical use: new insights for an old drug in clinical practice

Abstract

Metformin is generally recommended as first-line treatment in type 2 diabetes, especially in overweight patients, but in recent years new indications for its use have emerged. Metformin has been found to be safe and efficacious both as monotherapy and in combination with all oral antidiabetic agents and insulins. If metformin use during pregnancy and the lactation period is supported by few data, it could be indicated for women with polycystic ovary syndrome, since it could diminish circulating androgens and insulin resistance, thus ameliorating the ovulation rate. Metformin seems to reduce cancer risk, which appears to be increased in diabetics, and is a promising agent for oncoprevention and chemotherapy combinations. Moreover, metformin could find a place in the treatment of non-alcoholic fatty liver disease. Lactic acidosis could be decreased by avoiding metformin use in patients with hypovolemia, sepsis, renal impairment, hypoxic respiratory diseases and heart failure, in the preoperative period and before intravenous injection of contrast media.

Keywords: cancer; efficacy; metformin; safety; type 2 diabetes.

Figure 1

Metformin mechanism of action LKB1-AMPK – liver kinase B1-adenosine monophosphate activated protein kinase, PI3K – phosphoinositide 3-kinase inhibitor, IRS – insulin receptor substrate, mTOR – mammalian target of rapamycin, IGF-1 – insulin-like growth factor 1, PKA – protein kinase A, ERK – extracellular-signalregulated kinases, GLUT-4 – glucose transporter type 4, HMG-CoA – 3-hydroxy-3-methyl-glutaryl-CoA reductase, SREBP-1c – sterol regulatory element binding proteins