Related Experiment Video
Updated: Jan 21, 2026
08:56
Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes
Published on: October 10, 2025
647
The Association between Metformin Therapy and Lactic Acidosis
Isabelle H S Kuan1, Ruth L Savage2,3, Stephen B Duffull1
1School of Pharmacy, University of Otago, PO Box 56, Dunedin, New Zealand.
Drug Safety
|August 3, 2019
Summary
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.
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.
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