Insulin resistance is a clinical condition shared by many diseases besides type 2 diabetes (T2DM) such as obesity, polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD). Experimental evidence, produced over the years, suggests that metformin has many benefits in the treatment of these diseases. Metformin is a first-line drug in the treatment of overweight and obese type 2 diabetic patients, offering a selective pathophysiological approach by its effect on insulin resistance. Moreover, a number of studies have established the favorable effect of metformin on body weight, not only when evaluating BMI, but also if body mass composition is considered, through the reduction of fat mass. In addition, it reduces insulin resistance, hyperinsulinemia, lipid parameters, arterial hypertension and endothelial dysfunction. In particular, a new formulation of metformin extended-release (ER) is now available with different formulation in different countries. Metformin ER delivers the active drug through hydrated polymers which expand safe uptake of fluid, prolonging gastric transit and delaying drug absorption in the upper gastrointestinal tract. In addition, Metformin ER causes a small, but statistically significant decrease in BMI, when added to a lifestyle intervention program in obese adolescents. Because of the suggested benefits for the treatment of insulin resistance in many clinical conditions, besides type 2 diabetes, the prospective exists that more indications for metformin treatment are becoming a reality.