Many well-controlled diabetes patients who have stage-3 chronic kidney disease (CKD) do very well with metformin, but lately I’ve noticed a trend to stop the metformin in such patients. Is there any evidence of increasing adverse effects in this population? Would it be appropriate to continue use?
—Jason Collins, MD, Canton, Ohio

Metformin is an attractive pharmacologic option in the treatment of diabetes mellitus, particularly in overweight or obese patients. In this ever-growing group, data suggest that metformin monotherapy may decrease rates of mortality and MI (Cochrane Database Syst Rev. 2005;[3]:CD002966). One of the main drawbacks to the use of biguanides has been the risk of lactic acidosis. Phenformin, for example, was pulled from the U.S. market in 1976 because of high rates of lactic acidosis. Metformin, on the other hand, is felt to be quite safe when used for the appropriate patient. A meta-analysis of 176 trials from the late 1950s up to 2000 showed no cases of lactic acidosis in more than 17,000 patients taking metformin (Cochrane Database Syst Rev. 2002;[2]:CD002967). However, clinically significant lactic acidosis may occur in patients with certain predisposing conditions, including renal insufficiency (creatinine >1.4 mg/dL in women or >1.5 in men), congestive heart failure, and history of lactic acidosis, as well as in those at risk of renal insufficiency from IV iodinated contrast material or those seriously ill with hemodynamic or respiratory compromise. Thus, in your patient with stage-3 CKD, metformin may be contraindicated.
—Christopher Ruser, MD (99-10)

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