To check for renal insufficiency and ward off complications, such as lactic acidosis, I calculate the creatinine clearance of my diabetic patients taking metformin (Glucophage). At what creatinine clearance should I discontinue the medication? Does this value vary with gender or age?
—Ivanka Vassileva, MD, Lawton, Okla.

Clinicians are now being forced to navigate through often contradictory advice regarding the use of metformin. On a positive note, metformin monotherapy may decrease MI and death in overweight or obese diabetics (Cochrane Database Syst Rev. 2005;[3]:CD002966). And, in the appropriate patient, the risk of lactic acidosis may actually be quite low—in fact no worse than placebo (Cochrane Database Syst Rev. 2002;[2]:CD002967). The aforementioned salutary effects are often countered by literature suggesting that metformin continues to be “inappropriately” prescribed in many patients with absolute or relative contraindications (JAMA. 2002;19:2504-2505). These so-called inappropriate prescriptions took place in patients with congestive heart failure, renal insufficiency, or both.

The confusion results not just from metformin’s purported benefits vs. its feared complications and misuse, but also from the vagueness of published contraindications. Specifically, while most sources list clear serum creatinine cutoffs (>1.4 mg/dL in women and >1.5 in men), none lists creatinine clearance values below which the drug is contraindicated. Instead terms such as “renal disease,” “renal dysfunction,” or “abnormal creatinine clearance” are used (Metformin package insert, BMJ. 2003;326:4-5). This distinction may be particularly difficult in the elderly who at baseline may have higher rates of renal insufficiency and normal serum creatinine with abnormal creatinine clearances. In patients older than 80, for example, the package insert suggests that the drug should not be used unless the creatinine clearance is normal. It’s worth noting that in healthy subjects, the peak serum concentration of metformin rises precipitously as creatinine clearance falls below 60 mL/min.
—Christopher Ruser, MD (103-12)

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