title: Metformin-associated lactic acidosis: a rare or very rare clinical entity?
abstract: OBJECTIVE
  Lactic acidosis is a well recognized complication of biguanide therapy which is potentially serious. Although the prevalence of metformin-associated lactic acidosis (MALA) is much lower than that associated with phenformin, it is still being reported sporadically which raises concerns for the practising clinicians. We review the currently available world-wide data of the prevalence of MALA, the risk factors for its development and the current practical guidelines on the use of metformin to minimize the risk of this potential hazard.
  
  
  METHODS
  An extensive literature search was conducted from both Medline and Ovid (1965-98) using the following keywords: 'Type 2 diabetes mellitus', 'oral hypoglycaemic drugs', 'biguanides', 'metformin-associated lactic acidosis' and 'renal impairment'.
  
  
  RESULTS
  MALA was found to be a very rare clinical entity, being 20 times less common than phenformin-associated lactic acidosis. Amongst all the risk factors, renal impairment appears to be the major precipitating factor for the development of MALA in metformin-treated patients. We also found cases of MALA where no precipitating factors were identified and the underlying mechanism in these cases remains unclear. Practical recommendations of metformin use to minimize the risk of MALA have been listed based on previous reports.
  
  
  CONCLUSIONS
  The low prevalence of MALA is comparable to the prevalence of sulphonylurea-induced hypoglycaemia. Metformin has many beneficial metabolic effects in the management of Type 2 diabetes mellitus. Provided that the recommended guidelines for metformin use are strictly adhered to, its widespread use would be safe and the incidence of MALA will be further reduced.
authors.affiliation: Diabetes Unit, Medicine Directorate, Imperial College School of Medicine, Chelsea & Westminster Hospital, London. NN KA Chan@aol.com
authors.forename: N N
authors.initials: NN
authors.lastname: Chan
authors.forename: H P
authors.initials: HP
authors.lastname: Brain
authors.forename: M D
authors.initials: MD
authors.lastname: Feher
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced* / Q000453:epidemiology; D000284:Administration, Oral; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004739:England / Q000453:epidemiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008687:Metformin / Q000009:adverse effects*; D015995:Prevalence; D012307:Risk Factors
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin