Toxic Effects from Metformin Exposure

Abstract

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 ≤12 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.