title: Metformin-associated lactic acidosis requiring hospitalization. A national 10 year survey and a systematic literature review.
abstract: BACKGROUND
  Metformin is known to be rarely associated with lactic acidosis, a serious condition with a poor prognosis.
  
  
  OBJECTIVE
  To review the National Pharmacovigilance Network of the Italian Medicines Agency reporting cases of metformin-associated lactic acidosis.
  
  
  METHODS
  The National Pharmacovigilance Network of the Italian Medicines Agency, was searched for cases of lactic acidosis that occurred in a 10 years period (from November 2001 to October 2011). Data were analyzed, to identify associated clinical features. A systematic literature research was performed to identify other large case series on metformin associated lactic acidosis.
  
  
  RESULTS
  Metformin was the antidiabetic drug most frequently associated with lactic acidosis in the assessed period. Metformin-associated lactic acidosis was the most frequent serious adverse reaction related to metformin reported to the national authority (18.2% of all 650 adverse drug reactions reported). There were 59 cases of metformin-associated lactic acidosis (mortality rate of 25.4%). In most patients (89.8%) there was at least one risk factor for the occurrence of lactic acidosis. The predictors of death were low arterial blood pH and absence of acute renal failure. The systematic research of the literature identified only six case-series with more than 30 patients.
  
  
  CONCLUSIONS
  This is the second largest case series ever reported on metformin-associated lactic acidosis. We confirmed that this rare complication of metformin is frequently fatal. Death can be predicted when the patient arrive in the hospital with low pH and, not intuitively, if the patient has no acute kidney injury. Risk minimisation measures taken at national level to prevent this serious complication are described.
authors: Italian Medicines Agency, Rome, Italy.
authors: F
authors: F
authors: Renda
authors: P
authors: P
authors: Mura
authors: G
authors: G
authors: Finco
authors: F
authors: F
authors: Ferrazin
authors: L
authors: L
authors: Pani
authors: G
authors: G
authors: Landoni
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D005260:Female; D006306:Health Surveys; D006760:Hospitalization; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008687:Metformin / Q000009:adverse effects*; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D013997:Time Factors
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin