SynthesisDrug safety2019
The Association between Metformin Therapy and Lactic Acidosis.
Synthesis in Drug safety, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Pooled it
- Continuous ultrafiltration during extracorporeal circulation and its effect on lactatemia: A randomized controlled trial.PloS one · 2020Trial
- Toxicological profile of anti-diabetic drugs and emerging measures to reduce the toxic burden.Toxicology reports · 2026Review
- Pseudo-Ischemic ECG Changes in a Patient With Profound Mixed Metabolic Acidosis Due to Metformin Use.JACC. Case reports · 2026Article
- Unraveling the Mystery: COVID-19 and Diabetic Complications - A Journey from Pathophysiology to Treatment.Current diabetes reviews · 2026Review
- The Shengmai San Exerts Therapeutic Effects on Type 2 Diabetes by Modulating the PI3K/AKT/GSK3B Signaling Pathway.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Integrating network pharmacology and experimental validation to decipher the pharmacological mechanism of DXXK in treating diabetic kidney injury.Scientific reports · 2024Article
- Deliberate Self-Poisoning: Real-Time Characterization of Suicidal Habits and Toxidromes in the Food and Drug Administration Adverse Event Reporting System.Drug safety · 2023Article
- Metformin doses to ensure efficacy and safety in patients with reduced kidney function.PloS one · 2021Article
- Can Metformin Exert as an Active Drug on Endothelial Dysfunction in Diabetic Subjects?Biomedicines · 2020Review
- Review
- The pharmacokinetics of metformin in patients receiving intermittent haemodialysis.British journal of clinical pharmacology · 2020Article
- Extracorporeal treatment of metforminassociated lactic acidosis in clinical practice: a retrospective cohort study.European journal of clinical pharmacology · 2020Article
- Endocrine Therapy-related Endocrinopathies-Biology, Prevalence and Implications for the Management of Breast Cancer.Oncology & hematology review · 2020Article
- Clinical characteristics and short term outcomes after recovery from COVID-19 in patients with and without diabetes in Bangladesh.Diabetes & metabolic syndromeArticle
- Metformin exposure and the incidence of lactic acidosis in critically ill patients with T2DM: A retrospective cohort study.Science progressArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
INTRODUCTION AND
objectivesThere is increasing evidence to suggest that therapeutic doses of metformin are unlikely to cause lactic acidosis. The aims of this research were (1) to formally evaluate the association between metformin therapy and lactic acidosis in published case reports using two causality scoring systems, (2) to determine the frequency of pre-existing independent risk factors in published metformin-associated lactic acidosis cases, (3) to investigate the association between risk factors and mortality in metformin-associated lactic acidosis cases, and (4) to explore the relationship between prescribed metformin doses, elevated metformin plasma concentrations and the development of lactic acidosis in cases with chronic renal impairment.
methodsA systematic review was conducted to identify metformin-associated lactic acidosis cases. Causality was assessed using the World Health Organisation-Uppsala Monitoring Centre system and the Naranjo adverse drug reaction probability scale. Compliance to dosing guidelines was investigated for cases with chronic renal impairment as well as the association between steady-state plasma metformin concentrations prior to admission.
resultsWe identified 559 metformin-associated lactic acidosis cases. Almost all cases reviewed (97%) presented with independent risk factors for lactic acidosis. The prescribed metformin dose exceeded published guidelines in 60% of cases in patients with impaired kidney function. Metformin steady-state plasma concentrations prior to admission were predicted to be below the proposed upper limit of the therapeutic range of 5 mg/L.
conclusionsAlmost all cases of metformin-associated lactic acidosis reviewed presented with independent risk factors for lactic acidosis, supporting the suggestion that metformin plays a contributory role. The prescribed metformin dose, on average, exceeded the dosing recommendations by 1000 mg/day in patients with varying degrees of renal impairment but the predicted pre-admission plasma concentrations did not exceed the therapeutic range.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.