The DOI matches its Crossref record; 57 of the 58 references it cites were found in a registry or an index.
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to receive this medication on the basis of guidelines which, although well intentioned, are somewhat arbitrary and outdated based on modern assessments of renal status?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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Citations
Cites
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
(2002) · New England Journal of Medicine · doi:10.1056/nejmoa012512 · Cited by 19,011
Effects of Intensive Glucose Lowering in Type 2 Diabetes
(2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802743 · Cited by 7,888
10-year follow-up of intensive glucose control in type 2 diabetes
Holman, R. R., Paul, S. K., Bethel, M. A., Matthews, D. R., & Neil, H. A. W. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0806470 · Cited by 7,751
Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes
(2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802987 · Cited by 7,397
Glucose control and vascular complications in veterans with type 2 diabetes
Duckworth, W., Abraira, C., Moritz, T., Reda, D., Emanuele, N., Reaven, P. D., Zieve, F. J., Marks, J., Davis, S. N., Hayward, R., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808431 · Cited by 4,762
Nathan, D. M., Buse, J. B., Davidson, M. B., Ferrannini, E., Holman, R. R., Sherwin, R., & Zinman, B. (2009) · Diabetes Care · doi:10.2337/dc08-9025 · Cited by 3,834
Standards of medical care in diabetes 2010
American Diabetes Association (2010) · Diabetes Care · doi:10.2337/dc10-s011 · Cited by 3,470
Bailey, C. J., & Turner, R. C. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602293340906 · Cited by 1,726
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1 of the 58 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- National Institute for Health and Clinical Excellence, 2010, The Management of Type 2 Diabetes: 2010 NICE Guidelines [Internet]
- U.S. Food and Drug Administration, 2008, Guidance for Industry Diabetes Mellitus: Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes
Cited by
Sorted by citations
Inzucchi, S. E., Bergenstal, R. M., Buse, J. B., Diamant, M., Ferrannini, E., Nauck, M., Peters, A. L., Tsapas, A., Wender, R., & Matthews, D. R. (2012) · Diabetologia · doi:10.1007/s00125-012-2534-0 · Cited by 3,919
Self-citationManagement of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach
Inzucchi, S. E., Bergenstal, R. M., Buse, J. B., Diamant, M., Ferrannini, E., Nauck, M., Peters, A. L., Tsapas, A., Wender, R., & Matthews, D. R. (2012) · Diabetes Care · doi:10.2337/dc12-0413 · Cited by 3,207
Self-citationInzucchi, S. E., Bergenstal, R. M., Buse, J. B., Diamant, M., Ferrannini, E., Nauck, M., Peters, A. L., Tsapas, A., Wender, R., & Matthews, D. R. (2015) · Diabetes Care · doi:10.2337/dc14-2441 · Cited by 3,066
Self-citationInker, L. A., Astor, B. C., Fox, C. H., Isakova, T., Lash, J. P., Peralta, C. A., Tamura, M. K., & Feldman, H. I. (2014) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2014.01.416 · Cited by 1,828
KDOQI clinical practice guideline for diabetes and CKD: 2012 update
(2012) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2012.07.005 · Cited by 1,320
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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