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Cited by 432Diabetes Treatment and ManagementChronic Kidney Disease and DiabetesDiabetes Management and Research

Use of Metformin in the Setting of Mild-to-Moderate Renal Insufficiency

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Lipska, Kasia J., Bailey, Clifford J., Inzucchi, Silvio E.·2011·Diabetes Care
DOI 10.2337/dc10-2361PMC PMC3114336
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Abstract

A common clinical conundrum faces all U.S. practitioners treating patients with type 2 diabetes. Today’s U.S. Food and Drug Administration prescribing guidelines for metformin contraindicate its use in men and women with serum creatinine concentrations ≥1.5 and ≥1.4 mg/dL (≥132 and ≥123 µmol/L), respectively. In a patient tolerating and controlled with this medication, should it automatically be discontinued as the creatinine rises beyond these cut points over time? Stopping metformin often results in poorly controlled glycemia and/or the need for other agents with their own adverse-effect profiles. Moreover, is the now widespread use of estimated glomerular filtration rate (eGFR) in lieu of serum creatinine levels creating even more confusion, especially in those with abnormalities in one but not the other indirect measure of renal function? Indeed, more than a decade and a half after metformin became available in the U.S., debate continues over the best approach in these settings (1–3). How many patients are unable to receive this medication on the basis of guidelines which, although well intentioned, are somewhat arbitrary and outdated based on modern assessments of renal status? There is some evidence that early treatment with metformin is associated with reduced cardiovascular morbidity and total mortality in newly diagnosed type 2 diabetic patients (4). However, the data come from a small subgroup of a much larger trial. In contrast, despite multiple trials of intensive glucose control using a variety of glucose-lowering strategies, there is a paucity of data to support specific advantages with other agents on cardiovascular outcomes (5–7). In the original UK Prospective Diabetes Study (UKPDS), 342 overweight patients with newly diagnosed diabetes were randomly assigned to metformin therapy (8). After a median period of 10 years, this subgroup experienced a 39% ( P = 0.010) risk reduction for myocardial infarction and a …

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  • Lactic acidosis with metformin primarily occurs when eGFR is <30 mL/min/1.73 m2.

    “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 [101]

    In Conclusions and Recommendations (page unavailable), the paper recommends stopping metformin at eGFR <30 mL/min/1.73 m² and cautions about lactic acidosis in more advanced CKD. It does not report that lactic acidosis primarily occurs below that threshold; the cutoff is a prescribing recommendation, not an observed distribution of cases. (LLM, conf=0.83)

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  • Despite early concerns, the evidence for an increase in the risk of lactic acidosis with metformin is minimal.

    “Despite early concerns, the evidence for an increase in the risk of lactic acidosis with metformin is minimal.”

    From Diabetes in Older Adults: A Consensus Report (2012) · cites this paper as [94]

  • Age-related changes may translate into increased risk for hypoglycemia, potential need for reduced doses of certain medications, and attention to renal function to minimize side effects.

    “These changes may translate into increased risk for hypoglycemia, potential need for reduced doses of certain medications, and attention to renal function to minimize side effects94, 95.”

    From Diabetes in Older Adults: A Consensus Report (2012) · cites this paper as [94]

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Authors
Lipska, K. J., Bailey, C. J., & Inzucchi, S. E.
Affiliations
  • Yale University (US)
  • Aston University (GB)
Corresponding author
Inzucchi, Silvio E.
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2011-05-20
Volume
34
Issue
6
Pages
1431-1437
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc10-2361
PMC
PMC3114336
OpenAlex
W2154719797
Cited by
432
References
58
Citations by year
2026: 10 · 2025: 16 · 2024: 15 · 2023: 8 · 2022: 11 · 2021: 17 · 2020: 17 · 2019: 26 · 2018: 34 · 2017: 28 · 2016: 45 · 2015: 50 · 2014: 65 · 2013: 42 · 2012: 42
FWCI
6.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Care (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Aston Publications Explorer (Aston University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
metformin, renal failure, type 2 diabetes, serum creatinine, estimated glomerular filtration rate, metformin discontinuation, cardiovascular outcomes, glycemic control, UK Prospective Diabetes Study
MeSH terms
Contraindications, Acidosis, Lactic, Creatinine, Diabetes Mellitus, Type 2, Female, Glomerular Filtration Rate, Humans, Hypoglycemic Agents, Insulin, Male, Metformin, Myocardial Infarction, Practice Guidelines as Topic, Renal Insufficiency

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