METFORMIN: NONGLYCEMIC EFFECTS AND POTENTIAL NOVEL INDICATIONS

Abstract

Objective: Metformin is the most commonly prescribed drug for the treatment of type 2 diabetes because of its apparent robust effects in reducing cardiovascular risk. This review examines the current literature regarding the nonglycemic effects and potential novel indications for metformin.

Methods: Review of the literature, with a focus on metformin use in Stage 3 chronic kidney disease (CKD-3) and heart failure (HF).

Results: 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 use 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 literature review 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 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 HF; metformin therapy is associated with a reduction in newly incident HF and in HF mortality.

Conclusion: Metformin has a dominant position in the treatment of type 2 diabetes that is deserved due to its favorable and robust effects on cardiovascular risk.

Abbreviations: AMP = adenosine monophosphate BP = blood pressure CKD = chronic kidney disease CKD-3 = Stage 3 CKD eGFR = estimated glomerular filtration rate HDL = high-density lipoprotein HF = heart failure MAP = mean arterial pressure mVO2 = myocardial oxygen consumption T2DM = type 2 diabetes mellitus UKPDS = United Kingdom Prospective Diabetes Study.