Metformin in patientswith type 2 diabetes and kidney disease a systematic review

Silvio E. Inzucchi, Kasia J. Lipska, Helen Mayo, Clifford J. Bailey, Darren K. McGuire

Research output: Contribution to journalArticle

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Abstract

IMPORTANCE: Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis.

OBJECTIVE: To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function.

EVIDENCE ACQUISITION: In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining tometformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014.We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial.

RESULTS: Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety ofmetformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus-use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use.

CONCLUSIONS AND RELEVANCE: Available evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function.

Original languageEnglish (US)
Pages (from-to)2668-2675
Number of pages8
JournalJAMA - Journal of the American Medical Association
Volume312
Issue number24
DOIs
StatePublished - Dec 24 2014

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Metformin
Kidney Diseases
Lactic Acidosis
Type 2 Diabetes Mellitus
Kidney
Chronic Renal Insufficiency
Glomerular Filtration Rate
Manuscripts
MEDLINE
Pharmaceutical Preparations
Population
Observational Studies
Meta-Analysis
Lactic Acid
Language
Randomized Controlled Trials
Retrospective Studies
Pharmacokinetics
Clinical Trials
Databases

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Metformin in patientswith type 2 diabetes and kidney disease a systematic review. / Inzucchi, Silvio E.; Lipska, Kasia J.; Mayo, Helen; Bailey, Clifford J.; McGuire, Darren K.

In: JAMA - Journal of the American Medical Association, Vol. 312, No. 24, 24.12.2014, p. 2668-2675.

Research output: Contribution to journalArticle

Inzucchi, Silvio E. ; Lipska, Kasia J. ; Mayo, Helen ; Bailey, Clifford J. ; McGuire, Darren K. / Metformin in patientswith type 2 diabetes and kidney disease a systematic review. In: JAMA - Journal of the American Medical Association. 2014 ; Vol. 312, No. 24. pp. 2668-2675.
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N2 - IMPORTANCE: Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis.OBJECTIVE: To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function.EVIDENCE ACQUISITION: In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining tometformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014.We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial.RESULTS: Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety ofmetformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus-use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use.CONCLUSIONS AND RELEVANCE: Available evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function.

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