METFORMIN: NON-GLYCEMIC EFFECTS AND POTENTIAL NOVEL INDICATIONS

Metformin is the most commonly prescribed drug for the treatment of type 2 diabetes because of its apparent robust effects in reducing cardiovascular risk. The United Kingdom Prospective Diabetes Study suggests that metformin reduces the risk of myocardial infarction, and more recent retrospective studies have shown an association between metformin and a reduction in stroke, atrial fibrillation and all-cause mortality. The mechanism(s) explaining these putative benefits are not clear but may involve decreased energy intake (with attendant weight loss), improvement in lipids, and lowering of blood pressure; a review of selected literature suggests that metformin lowers blood pressure when it is elevated, but not when it is normal. Metformin appears to be safe when given to patients with Stage 3 chronic kidney disease (CKD-3). In addition, there is evidence that individuals with CKD-3, who are at increased cardiovascular risk, stand to benefit from metformin therapy. Lactic acidosis is an extremely remote and probably avoidable risk; measurement of plasma metformin levels and more frequent monitoring of renal function may be useful in selected patients with CKD-3 who are treated with metformin. Finally, there is evidence that metformin is safe in patients with heart failure; metformin therapy is associated with a reduction in newly incident heart failure and in heart failure mortality.