title: Metformin accumulation without hyperlactataemia and metformin-induced hyperlactataemia without metformin accumulation.
abstract: OBJECTIVE
  These case reports demonstrate that, at the individual level, blood metformin concentrations and metformin effects on lactate do not always correlate.
  
  
  METHODS
  We report here on two unusual cases: metformin accumulation in the absence of hyperlactataemia; and metformin-induced hyperlactataemia with no metformin accumulation.
  
  
  RESULTS
  Patient #1 presented with severe kidney failure, severe acidosis (pH: 7.04), normal lactataemia (0.90 mmol/L) and marked metformin accumulation. Patient #2 presented with hyperlactataemia, even after dose reduction, during otherwise well-tolerated metformin treatment. Arterial lactate levels were 8.8, 8.2 and 4.7 mmol/L during metformin therapy with daily doses of 2550, 1700 and 850 mg, respectively. After withdrawal, metformin was reintroduced for 5-day periods at 500 mg/day up to 2000 mg/day with washout intervals. Lactate concentration, normal at baseline, rapidly exceeded 2 mmol/L after metformin administration.
  
  
  CONCLUSIONS
  These clinical data suggest a new concept for metformin therapy: there may be either resistance or, conversely, hypersensitivity to metformin effects on lactate generation according to the individual patient.
authors.affiliation: Service d'endocrinologie et de nutrition, hôpital Sud, centre hospitalier universitaire, 80054 Amiens cedex 1, France; Unité INSERM 1088, Université de Picardie-Jules-Verne, Amiens, France. Electronic address: lalau.jean-daniel@chu-amiens.fr.
authors.forename: J D
authors.initials: JD
authors.lastname: Lalau
authors.affiliation: Service d'endocrinologie et de nutrition, hôpital Sud, centre hospitalier universitaire, 80054 Amiens cedex 1, France.
authors.forename: M L
authors.initials: ML
authors.lastname: Azzoug
authors.affiliation: Service d'endocrinologie et de nutrition, hôpital Sud, centre hospitalier universitaire, 80054 Amiens cedex 1, France; Unité INSERM 1088, Université de Picardie-Jules-Verne, Amiens, France.
authors.forename: F
authors.initials: F
authors.lastname: Kajbaf
authors.affiliation: Service d'endocrinologie et de nutrition, centre hospitalier universitaire du Kremlin-Bicêtre, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Briet
authors.affiliation: Service d'endocrinologie et de nutrition, hôpital Sud, centre hospitalier universitaire, 80054 Amiens cedex 1, France; Unité INSERM 1088, Université de Picardie-Jules-Verne, Amiens, France.
authors.forename: R
authors.initials: R
authors.lastname: Desailloud
mesh_terms: D000140:Acidosis, Lactic / Q000097:blood / Q000139:chemically induced*; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity; D004351:Drug Resistance; D005260:Female; D006801:Humans; D065906:Hyperlactatemia / Q000097:blood / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D019344:Lactic Acid; D008687:Metformin
keywords: Hyperlactataemia; Lactate; Lactic acidosis; Metformin; Type 2 diabetes