Review: 50 years later: is metformin a vascular drug with antidiabetic properties?

Abstract

Since the clinical demonstration of a protective effect of metformin against chronic diabetic angiopathy in the United Kingdom Prospective Diabetes Study, many data have accumulated which confirm such effects in acute or chronic situations as diverse as ischaemia, non-diabetic insulin resistant states and diabetes. Recent years have provided several mechanisms of action and further documented some unique properties of this compound such as improvements in microcirculatory flow, glycation and oxidative stress. In particular, the latter effect could be shown in mitochondria, i.e. the most important sources of reactive oxygen species in diabetes. Specific, non-toxic actions of metformin at the level of the mitochondrial respiratory chain also prevent apoptosis, another mechanism to explain the long-term protection afforded by metformin. Noteworthy, most of these effects of metformin are unrelated to drug dosage and largely independent of its antihyperglycaemic effect (intrinsic properties). These new data open potential avenues for larger therapeutic utilisations of this drug, 50 years after its launch for the treatment of type 2 diabetes.