Ask the Experts - Metformin in Patients with Cardiovascular Disease?
A 65-year-old woman with type 2 diabetes and a history of cardiovascular complications (congestive heart failure [New York Heart Association class III], post-coronary artery bypass graft with multiple myocardial scars after anterior wall/posterior wall myocardial infarctions, and significant peripheral arterial occlusive disease [mainly small vessel disease] with intermittent resting pain in the lower extremities) was being treated with 850 mg of metformin twice daily when she was referred to our cardiac rehabilitation clinic. I believe that the metformin therapy in this case might provoke tissue acidosis and worsen her condition. Her blood glucose is not well controlled with this regimen (150-250 mg/dL). Her renal function is good, with no other significant disease states. Would you use a different oral antidiabetic in this situation?

Michael McCabe, MD



Metformin, a biguanide, is widely used to treat diabetes and has an excellent overall safety record. Lactic acidosis was a serious and life-threatening complication with the older biguanide, phenformin, which was removed from the market. Lactic acidosis related to metformin is very rare. It results when the breakdown of sugars to energy in the mitochondria of the cells is impaired. Lactic acid accumulates as the partially metabolized breakdown product of glucose. Very rarely this can occur in individuals with a genetically unusual sensitivity to the drug. Otherwise, the problem occurs only in the presence of an unusual accumulation of the drug in the blood.

Since metformin is cleared from the body through the kidneys, caution should be used in administering metformin when kidney function is impaired or when the kidneys are at a high risk of becoming impaired. Metformin does not cause kidney damage, but the drug is avoided in patients with diabetes with significant kidney disease. Patients with very poor heart function or significant heart failure often do not perfuse their kidneys adequately. Kidney function in these individuals may change relatively rapidly and, as a result, metformin levels in the blood may increase unexpectedly to dangerous levels. Metformin is probably best avoided in that situation. Some other medical conditions, such as recurrent pancreatitis, cause lactic acidosis and have the potential to impair kidney function. Again, the drug should not be used in individuals at high risk for these problems. In patients with congestive heart failure, the clinician needs to determine if the degree of cardiac impairment is enough to place kidney function at risk. If it is, then metformin should be avoided. The so-called "glitazone" class of drugs should also be avoided in these situations because of the drugs' tendency to contribute to salt and fluid retention. Sulfonylureas and insulin remain the drugs of choice for such patients.