Metformin: Should it be the first therapeutic option in the patient with high-risk diabetes?

Abstract

Diabetes mellitus (DM) is classically defined as a metabolic disorder characterized by the presence of hyperglycemia secondary to defects in insulin secretion or action. Type 2 diabetes (DM2), the most prevalent entity, is frequently associated with other components of the metabolic syndrome and its etiopathogenesis shows different pathophysiological alterations, insulin resistance being one of the central mechanisms. Diabetes mellitus is undoubtedly one of the cardiovascular risk factors with greatest impact, and cardiovascular disease is the most frequent cause of death among patients with diabetes. Although the role of glycemic control on cardiovascular effect is controversial, there is a well known association between intensified control and the reduction of other complications with a high burden of morbidity and mortality, such as retinopathy, peripheral nephropathy and diabetic nephropathy. Metformin is one of the most widely used drugs as first-line treatment for the management of hyperglycemia in patients with DM2, due to its proven efficacy in lowering blood glucose (it reduces HbA1c between 1% and 2%, depending on its initial value), added to its adequate safety profile without risk of hypoglycemia and with few serious adverse events observed after more than 60 years of experience in its use. It has few relevant drug interactions in routine clinical practice and its low cost allows wide access as the first tool for metabolic control. Metformin reduces blood glucose by improving peripheral insulin sensitivity, mainly decreasing hepatic glucose production and increasing glucose uptake by the skeletal muscle. These effects are produced through the regulation of the energy balance and redox potential at the mitochondrial level. In addition, it exerts an important action on the gastrointestinal tract, modulating GLP-1, bile acid content and microbiota composition. On the other hand, it would modulate inflammation by direct and indirect effects on cells of the immune system in different organs such as the liver, muscle and digestive tract, all mechanisms