Metformin: Nonglycemic Effects and Potential Novel Indications |
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| Institution: | 1. From the University of Kansas School of Medicine, Division of Endocrinology, Metabolism and Genetics, Kansas City, Kansas.;1. Division of Cardiology, St Michael''s Hospital, Toronto, Ontario, Canada;2. University of Toronto, Toronto, Ontario, Canada;3. Canadian Heart Research Centre, Toronto, Ontario, Canada;4. Division of Endocrinology and Metabolism, St Michael''s Hospital, Toronto, Ontario, Canada;5. Brigham and Women''s Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts, United States;6. The Credit Valley Hospital and St Michael''s Hospital, Toronto, Ontario, Canada;7. Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia, Canada |
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| 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 monophosphateBP = blood pressureCKD = chronic kidney diseaseCKD-3 = Stage 3 CKDeGFR = estimated glomerular filtration rateHDL = high-density lipoproteinHF = heart failureMAP = mean arterial pressuremVO2 = myocardial oxygen consumptionT2DM = type 2 diabetes mellitusUKPDS = United Kingdom Prospective Diabetes Study |
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