Metformin accumulation without hyperlactataemia and metformin-induced hyperlactataemia without metformin accumulation

Diabetes Metab. 2014 Jun;40(3):220-3. doi: 10.1016/j.diabet.2013.12.003. Epub 2014 Jan 10.

Abstract

Aim: 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.

Conclusion: 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.

Keywords: Hyperlactataemia; Lactate; Lactic acidosis; Metformin; Type 2 diabetes.

Publication types

  • Case Reports

MeSH terms

  • Acidosis, Lactic / blood
  • Acidosis, Lactic / chemically induced*
  • Aged
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Administration Schedule
  • Drug Hypersensitivity
  • Drug Resistance
  • Female
  • Humans
  • Hyperlactatemia / blood
  • Hyperlactatemia / chemically induced*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / metabolism
  • Lactic Acid / blood*
  • Male
  • Metformin / administration & dosage
  • Metformin / adverse effects*
  • Metformin / metabolism
  • Middle Aged
  • Treatment Outcome

Substances

  • Hypoglycemic Agents
  • Lactic Acid
  • Metformin