Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus

Salpeter, Shelley R; Greyber, Elizabeth; Pasternak, Gary A; Salpeter (posthumous), Edwin E

doi:10.1002/14651858.cd002967.pub4

Cited by 893Diabetes Treatment and ManagementDiabetes Management and ResearchMetabolism, Diabetes, and Cancer

Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus

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Salpeter, Shelley R, Greyber, Elizabeth, Pasternak, Gary A, Salpeter (posthumous), Edwin E·2010·Cochrane Database of Systematic Reviews

DOI 10.1002/14651858.cd002967.pub4PMC PMC7138050

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Abstract

Background Metformin is an oral anti-hyperglycemic agent that has been shown to reduce total mortality compared to other anti-hyperglycemic agents, in the treatment of type 2 diabetes mellitus. Metformin, however, is thought to increase the risk of lactic acidosis, and has been considered to be contraindicated in many chronic hypoxemic conditions that may be associated with lactic acidosis, such as cardiovascular, renal, hepatic and pulmonary disease, and advancing age. Objectives To assess the incidence of fatal and nonfatal lactic acidosis, and to evaluate blood lactate levels, for those on metformin treatment compared to placebo or non-metformin therapies. Search strategy A comprehensive search was performed of electronic databases to identify studies of metformin treatment. The search was augmented by scanning references of identified articles, and by contacting principal investigators. Selection criteria Prospective trials and observational cohort studies in patients with type 2 diabetes of least one month duration were included if they evaluated metformin, alone or in combination with other treatments, compared to placebo or any other glucose-lowering therapy. Data collection and analysis The incidence of fatal and nonfatal lactic acidosis was recorded as cases per patient-years, for metformin treatment and for non-metformin treatments. The upper limit for the true incidence of cases was calculated using Poisson statistics. In a second analysis lactate levels were measu…

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The occurrence of lactic acidosis with metformin is very rare.
“However, the occurrence of this complication is very rare (100) and primarily occurs when the estimated glomerular filtration rate (eGFR) is <30 mL/ min/1.73 m 2 (101).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [100]

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Authors: Salpeter, S. R., Greyber, E., Pasternak, G. A., & Salpeter (posthumous), E. E.
Affiliations: Santa Clara Valley Medical Center (US)
Venue: Cochrane Database of Systematic Reviews
Publisher: John Wiley & Sons, Ltd
Published: 2010-01-20
Issue: 4
Pages: CD002967-CD002967
ISSN: 1361-6137 (ISSN-L)
DOI: 10.1002/14651858.cd002967.pub4
PMC: PMC7138050
OpenAlex: W1893959718
Cited by: 893
References: 23
Citations by year: 2026: 7 · 2025: 17 · 2024: 29 · 2023: 24 · 2022: 29 · 2021: 40 · 2020: 51 · 2019: 54 · 2018: 53 · 2017: 53 · 2016: 52 · 2015: 59 · 2014: 67 · 2013: 50 · 2012: 69
Type: reference entry
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Cochrane Database of Systematic Reviews (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: lactic acidosis, type 2 diabetes, drug safety, hypoxemia, anti-hyperglycemic agents, adverse drug reactions, fixed effects model, Poisson statistics
MeSH terms: Contraindications, Acidosis, Lactic, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Metformin, Prospective Studies, Risk, Cohort Studies, Incidence, Lactic Acid

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Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus

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