Metformin doesn’t cause kidney dysfunction but it may cause lactic acidosis. In patients with advanced kidney disease, that’s rare, with an estimated prevalence of 2-5 cases per 100,000, but is associated with a high fatality rate of 50%. It’s unclear how metformin causes lactic acidosis — it isn’t necessarily related to the accumulation of metformin as was previously thought, but tissue hypoxia has been noted to bea trigger. So metformin should be discontinued when tissue hypoxia is suspected, regardless of renal function.

The manufacturer’s insert notes that metformin is contraindicated if the serum creatinine is above the normal range: 134 µmol/L in men or 126 µmol/L in women. The concentration of serum creatinine doesn’t truly reflect the patient’s renal function, especially in the elderly and in patients with poor muscle mass, and it’s recommended that GFR should be estimated using either the Cockcroft-Gault or Modification of Diet in Renal Disease Study (MDRD) equation. Metformin should be stopped when the GFR is less than 30 mL/min or when the patient has progressed to stage 4 chronic kidney disease. There’s still some controversy among experts when the GFR is between 30-60 mL/min (stage 3 chronic kidney disease) because of the proven cardiovascular benefits of metformin in the United Kingdom Prospective Diabetes Study (UKPDS). In this range, metformin should be used with caution and should be withdrawn immediately during periods of suspected tissue hypoxia — i.e. shock, sepsis, myocardial infarction, etc.

Jones et al (BMJ 2003; 326:4-5) suggested revised contraindications that are simple to follow:

• Stop metformin if serum creatinine is 150 µmol/L or higher, and especially if the renal dysfunction is progressive
• Most important is to stop metformin during episodes of hypoxia — shock, MI, sepsis
• Withhold for three days after contrast medium is used and resume after checking renal function
• Stop metformin two days before general anesthesia and resume when renal function is stable.

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