Metformin has become a valuable first-line agent in treating type 2 diabetes. Two recent reports serve as reminders that there may be adverse effects with this drug.

• Researchers at the University of Pittsburgh evaluated prescribing practices to see whether doctors were following the contraindications and precautions associated with metformin. The primary adverse effect of metformin is lactic acidosis, which is seen in patients with renal insufficiency and those undergoing radiologic procedures using contrast dye. Thus those conditions are listed as a contraindication and precaution, respectively, for metformin use.

  The researchers found that more than one-quarter of the patients studied had been prescribed metformin even though they had at least one absolute contraindication to the drug. The most common contraindication was elevated serum creatinine concentration, indicative of kidney dysfunction; the risk here is of damaging the kidneys due to excessive accumulation of lactic acid in the bloodstream. Other contraindications to metformin use are liver disease, heart failure or recent heart attack, breathing difficulties, alcohol abuse and severe infection.

  In addition, 37 percent of the patients studied were taking metformin even though they had received contrast media.

• The second report describes vitamin B12 deficiency in patients with type 2 diabetes who take metformin. It is estimated that 10 to 30 percent of patients taking metformin develop vitamin B12 deficiency. In people taking metformin who have a reasonable dietary intake of the vitamin, the deficiency can take 10 to 15 years to develop. It is not known how metformin causes the deficiency, but it may be related to changes in absorption of the vitamin.

  This report urges doctors to look for signs and symptoms of B12 deficiency in their patients taking metformin. These include fatigue, weakness, nausea, constipation, flatulence, loss of appetite or weight loss. Neurolgic changes such as numbness and tingling in the hands and feet may also signal B12 deficiency.

Related information Treatment - Oral Medications

Sources:

• Calabrese AT, Coley KC, DaPos SV, et al. Evaluation of prescribing practices - risk of lactic acidosis with metformin therapy. Archives of Internal Medicine, Feb. 25, 2002;162(4):434-437. (Abs.)
• Gilligan MA. Metformin and vitamin B12 deficiency. Archives of Internal Medicine, Feb. 25, 2002;162(4).
• National Institutes of Health. Dietary supplements - vitamin B12. NIH Clinical Center Fact Sheet, August 2001.