title: Metformin in patients with type 2 diabetes and kidney disease: a systematic review.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, 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 1.73 m2). 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 of metformin 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
  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.
authors.affiliation: Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Silvio E
authors.initials: SE
authors.lastname: Inzucchi
authors.affiliation: Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Kasia J
authors.initials: KJ
authors.lastname: Lipska
authors.affiliation: Health Sciences Digital Library and Learning Center, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Helen
authors.initials: H
authors.lastname: Mayo
authors.affiliation: School of Life & Health Sciences, Aston University, Birmingham, United Kingdom.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Bailey
authors.affiliation: Division of Cardiology, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Darren K
authors.initials: DK
authors.lastname: McGuire
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced*; D000075202:Contraindications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005919:Glomerular Filtration Rate; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008687:Metformin / Q000009:adverse effects* / Q000627:therapeutic use; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D012306:Risk
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin