Metformin use among individuals at risk for type 2 diabetes.

Excess total and cardiovascular morbidity and mortality remain very high among those with type 2 diabetes versus those without diabetes. Clinical trials to lower blood glucose have been disappointing probably because the participants were too late in the natural history of diabetes and already had extensive vascular disease. Insulin resistance measured simply by elevated fasting blood insulin is an early marker of β-cell stress and peripheral insulin resistance. Metformin will prevent development of diabetes among patients with impaired fasting glucose but only for the short term. Metformin reduces risk of coronary heart disease. The drug is safe, low cost, and may also prevent cancer. The combination of diet and exercise followed by metformin in the early phase of "insulin resistance" may reduce or delay both atherosclerosis and arteriosclerosis complications associated with diabetes. Preventive therapy must begin much earlier than before clinical diagnosis of diabetes and aim to initially lower blood insulin levels or insulin resistance.