Toxic effects from metformin exposure

BACKGROUND: The major risk associated with metformin is lactic acidosis. The incidence of lactic acidosis is not clear. Hypoglycemia is not expected to be a major concern after metformin exposure. OBJECTIVE: This study assessed the demographics, toxic effects, and clinical syndromes of metformin exposures reported to poison centers nationally. METHODS: The Toxic Exposure Surveillance System (TESS) of the American Association of Poison Control Centers was searched for all metformin-only exposures occurring from January 1, 1996, through December 31, 2000. RESULTS: There were 10 958 526 total poisoning exposures reported to TESS during the study period. Of those, 4072 cases met the study criteria. Exposures occurred in 2421 (59%) women and were categorized in all patients as acute (3074; 75%), acute-on-chronic (767; 19%), chronic (200; 5%), and chronicity unknown (31; 1 %). Children less than or equal to12 years old experienced few adverse outcomes and no deaths. There were 20 moderate-effect outcomes (1.8%) and 2 major-effect outcomes (0.2%) in children <6 years old and 4 moderate-effect outcomes (2.3%) and no major-effect outcomes in children 6-12 years old. In the adult population, the adverse outcomes were distributed evenly across the age span, with a trend toward more serious outcomes in the elderly. There were 9 deaths (0.2%), 32 major-effect cases (0.8%), and 187 moderate-effect cases (4.6%). In all age groups, acidosis was rare (n = 68; 1.6%). Hypoglycemia is more common than previously reported (n = 112; 2.8%). Clinical effects associated with a major outcome or death were hyperglycemia, acidosis, elevated anion gap, elevated creatinine, hypotension, and coma. CONCLUSIONS: Severe adverse events after exposure to metformin are not common, occurring in approximately 1% of cases; this is in agreement with previous reports. The presence of hypotension, acidosis, elevated anion gap, hyperglycemia, and coma may be prognostic of severe or fatal outcome.