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Use of Metformin in the Setting of Mild-to-Moderate Renal Insufficiency
Open accessAbstract
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to receive this medication on the basis of guidelines which, although well intentioned, are somewhat arbitrary and outdated based on modern assessments of renal status?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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“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]
Experimental — accuracy not yet measuredIn the citing paper
“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]
In the citing paper
“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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- U.S. Food and Drug Administration, 2008, Guidance for Industry Diabetes Mellitus: Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes
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Metadata
- Authors
- Lipska, K. J., Bailey, C. J., & Inzucchi, S. E.
- Affiliations
- Yale University (US)
- Aston University (GB)
- Corresponding author
- Inzucchi, Silvio E.
- 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
- 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
- hybrid
- doi.org
- 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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