Metformin Beyond Diabetes: New Life for an Old Drug

Abstract

Metformin is a widely used drug in the therapy of patients affected by diabetes mellitus. Although some caution is needed in the very old, advanced age per se does not represent a contraindication to metformin use. Despite the fact that its precise mechanism of action it is not completely elucidated, long-term treatment with this drug in monotherapy, improves glycaemic control and reduces cardiovascular mortality in overweight type 2 diabetic patients. Experimental evidence produced over the years suggests that metformin may be useful in some clinical conditions different from diabetes mellitus. In the present review we have examined currently available data about the possible use of metformin as an effective therapeutical agent in pathological conditions different from type 2 diabetes mellitus. On the basis of our investigation, the use of metformin can be suggested in overweigth patients affected by impaired glucose tolerance and/or fasting hyperglycaemia and in subjects affected by polycystic ovary syndrome, while further data are needed in order to prescribe such a drug in patients affected by non-alcoholic steato-hepatitis and in HIV patients on antiretroviral therapy.

Orphan Nuclear Receptor Small Heterodimer Partner Negatively Regulates Growth Hormone-mediated Induction of Hepatic Gluconeogenesis through Inhibition of Signal Transducer and Activator of Transcription 5 (STAT5) Transactivation

“…Metformin is an anti-diabetic agent that ameliorates hyperglycemia by decreasing hepatic glucose production (9,10). Liver kinase B1 is a downstream effector of metformin and activates AMP-activated protein kinase (AMPK) in the liver, thereby regulating glucose homeostasis (10,11).…”

Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state

“…Metformin is currently the drug of first choice for the treatment of type 2 diabetes, being prescribed to at least 120 million people worldwide. As demonstrated in large prospective controlled clinical trials, metformin improves glycemic control and reduces cardiovascular mortality in overweight type 2 diabetic patients (1) and is also used to prevent type 2 diabetes (2). However, the molecular mechanisms of metformin action are not well understood.…”

Individualizing Chemotherapy using the Anti-Diabetic Drug, Metformin, as an “Adjuvant”: An Exploratory Study

“…Around 2006, the potential for the usage of metformin in the control and management of cancer was recognized [18,19]. Indeed, numerous observational studies reported decreased cancer incidence and cancer-related mortality in adult diabetics receiving pharmacologically relevant standard doses of metformin (1500 to 2250 mg/day) [19].…”