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The Association between Metformin Therapy and Lactic Acidosis.

Isabelle H S Kuan1, Ruth L Savage2,3, Stephen B Duffull1

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Metformin is unlikely to cause lactic acidosis alone; most cases involve pre-existing risk factors. High metformin doses were common in patients with kidney issues, but plasma levels remained therapeutic.

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Area of Science:

  • Pharmacology
  • Clinical Toxicology
  • Nephrology

Background:

  • Metformin is a widely used antidiabetic drug.
  • Lactic acidosis is a rare but serious adverse effect associated with metformin.
  • Evidence suggests metformin may only contribute to lactic acidosis in the presence of other risk factors.

Purpose of the Study:

  • To evaluate the association between metformin and lactic acidosis using causality scoring.
  • To determine the frequency of independent risk factors in metformin-associated lactic acidosis cases.
  • To investigate the relationship between metformin dosage, plasma concentrations, risk factors, and mortality.

Main Methods:

  • Systematic review of published metformin-associated lactic acidosis cases.
  • Causality assessment using WHO-Uppsala and Naranjo scales.
  • Analysis of dosing compliance and plasma metformin concentrations in renal impairment.

Main Results:

  • 559 metformin-associated lactic acidosis cases were identified.
  • 97% of cases had independent risk factors for lactic acidosis.
  • 60% of cases with renal impairment exceeded metformin dosing guidelines, yet plasma concentrations were therapeutic.

Conclusions:

  • Metformin-associated lactic acidosis is strongly linked to independent risk factors.
  • Exceeding metformin dosage recommendations is common in renal impairment.
  • Therapeutic plasma metformin concentrations do not appear to be a primary driver of lactic acidosis.