Selected topics: toxicologyMetformin-associated lactic acidosis
Introduction
In 1995, metformin (dimethylbiguanide) was introduced in the United States after approval by the U.S. Food and Drug Administration as an oral hypoglycemic agent for the treatment of diabetes mellitus 1, 2. Food and Drug Administration approval of its predecessor biguanide, phenformin, was revoked in the 1970s after reports of fatalities linked to lactic acidosis induced by the agent (3). Metformin associated with lactic acidosis has also been reported, but the incidence of this complication is substantially less, estimated to be approximately three cases per 100,000 patient years, compared to a 10- to 20-fold higher incidence for phenformin 4, 5, 6. The time course of the metabolic derangements characterizing metformin-associated lactic acidosis (MALA) has not been well described, undoubtedly because of its rarity. Some observers have doubted a causal relationship between metformin and lactic acidosis, instead attributing the acidosis to coincidentally occurring alternative explanations 7, 8.
Section snippets
Case presentation
A 76-year-old, 46-kg woman presented to the Emergency Department (ED) complaining of nausea, anorexia, vague abdominal pain, and malaise. Her past medical history included an 18-year history of noninsulin-dependent diabetes mellitus and a 3-year history of hypertension. She denied recent or past alcohol use. Two years prior to this admission she had undergone coronary artery bypass surgery after a myocardial infarction. She had been taking metformin, 850 mg twice daily, for the past 3 years;
Discussion
Numerous clinical studies, including randomized, double-blind, placebo-controlled trials, have demonstrated that metformin can substantially lower blood glucose and glycosylated hemoglobin levels in patients with diabetes mellitus 10, 11, 12, 13. Unlike sulfonylurea agents, the mechanism does not involve stimulation of insulin secretion by the endocrine pancreas, and hypoglycemia is not observed (14). Available information suggests that the antihyperglycemic effect of metformin is instead due
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