Metformin: Pharmacological Action and Nutritional Metabolism

Abstract

Metformin is a biguanide, a drug class of herbal origin that has been widely used to treat diabetes since the 1950s. Two other biguanides were withdrawn from clinical use because they caused lactic acidosis. Currently, metformin is the first-line medication for treatment of type 2 diabetes mellitus (T2DM) in most guidelines. Animal and human studies have shown that metformin acts in the liver, where it inhibits gluconeogenesis through multiple pathways. In addition, metformin has been shown to be an insulin sensitizer, likely acting in the gut lumen through multiple mechanisms. However, a full understanding of metformin's mechanism of action remains elusive, and the drug's effects are likely pleiotropic. In view of its efficacy and safety for T2DM, attention has been given to the repurposing of metformin as a component of adjunct therapy for cancer, age-related diseases, and inflammatory diseases. In this review, we outline the effectiveness, safety, and precautions in the clinical use of metformin, and discuss recent advances in our understanding of the mechanisms of its action.