title: Mortality rate in so-called "metformin-associated lactic acidosis": a review of the data since the 1960s.
abstract: OBJECTIVE
  The aim of this study is to study the mortality rate in so-called "metformin-associated lactic acidosis" (MALA) from the 1960s to date and to establish whether the rate has changed over time.
  
  
  METHODS
  We systematically searched two data sources for information on mortality in cases recorded as MALA: (i) series in the scientific literature containing over 20 case reports and (ii) a large pharmacovigilance database (containing 869 reports logged between 1995 and 2010).
  
  
  RESULTS
  We identified 12 series published between the 1960s and 2013 (mean ± SD [range] number of case reports per series: 51.4 ± 24.7) [23-110]) and 722 case reports with a specified outcome in the pharmacovigilance database. None of the sources specified all three criteria for determining MALA (i.e., the pH level, blood lactate concentration, and blood metformin concentration). The mortality rate in the literature series ranged from 3% to 61%. The value was 47% in the earliest series (1960-1993) and below 25% in the last series. The mean pH per literature series varied widely (from 6.89 to 7.20). The mortality rates in the pharmacovigilance database fell from around 50% to 25% over the study period, while the pH remained in a narrow range (6.94-7.07).
  
  
  CONCLUSIONS
  The overall mortality rate for MALA was around 50% during the period 1960-2000 but has since fallen to around 25%.
authors: Service d'Endocrinologie-Nutrition, Hôpital Sud, Amiens, France.
authors: Farshad
authors: F
authors: Kajbaf
authors: Jean-Daniel
authors: JD
authors: Lalau
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced* / Q000401:mortality*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008687:Metformin / Q000009:adverse effects* / Q000627:therapeutic use; D060735:Pharmacovigilance
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: lactate; lactic acidosis; metformin; pharmacoepidemiology; prognosis; type 2 diabetes