Metformin in prediabetes: key mechanisms for the prevention of diabetes and cardiometabolic risks

Abstract

Today, prediabetes is regarded by the world medical community as early diabetes mellitus. The accumulated research evidence shows that prediabetes is characterized by a spectrum of complications that are similar to those of diabetes mellitus, which means that the deterioration of cardiovascular prognosis starts already at the stage of prediabetes. In the current timeframe, metformin is actually the only drug that is widely prescribed for the treatment of prediabetes to prevent type 2 diabetes mellitus and cardiovascular diseases associated with insulin resistance and hyperinsulinemia. Meanwhile, metabolically unhealthy obesity characterized by hyperinsulinemia and insulin resistance is associated with a significantly unfavourable course of prediabetes, as well as the highest risk of developing both type 2 diabetes mellitus and cardiovascular diseases, development/ progression of chronic kidney disease. The theme of this review is the priority of metformin for the management of the most prognostically unfavourable phenotypes of prediabetes. The review is also devoted to the description of the most significant mechanisms that provide effects of metformin underlying the management of key disorders that determine the unfavourable prognosis of prediabetes. In particular, it sets forth the role of unhealthy nutrition, its effects on the development of imbalance of the composition of gut microbiota, which, in turn, entails a cascade of metabolic disorders underlying the development of metabolic ill health. The review sets forth the key role of metformin as a drug that protects against the development of these disorders. The information presented in this review will be useful to personalize the choice of both the scope and nature of interventions in patients with different phenotypic characteristics.

Keywords

• prediabetes
• microbiota
• metformin
• incretins
• lipopolysaccharides