title: Clinical Outcomes of Metformin Use in Populations With Chronic Kidney Disease, Congestive Heart Failure, or Chronic Liver Disease: A Systematic Review.
abstract: BACKGROUND
  Recent changes to the U.S. Food and Drug Administration boxed warning for metformin will increase its use in persons with historical contraindications or precautions. Prescribers must understand the clinical outcomes of metformin use in these populations.
  
  
  OBJECTIVE
  To synthesize data addressing outcomes of metformin use in populations with type 2 diabetes and moderate to severe chronic kidney disease (CKD), congestive heart failure (CHF), or chronic liver disease (CLD) with hepatic impairment.
  
  
  METHODS
  MEDLINE (via PubMed) from January 1994 to September 2016, and Cochrane Library, EMBASE, and International Pharmaceutical Abstracts from January 1994 to November 2015.
  
  
  METHODS
  English-language studies that: 1) examined adults with type 2 diabetes and CKD (with estimated glomerular filtration rate less than 60 mL/min/1.73 m2), CHF, or CLD with hepatic impairment; 2) compared diabetes regimens that included metformin with those that did not; and 3) reported all-cause mortality, major adverse cardiovascular events, and other outcomes of interest.
  
  
  METHODS
  2 reviewers abstracted data and independently rated study quality and strength of evidence.
  
  
  RESULTS
  On the basis of quantitative and qualitative syntheses involving 17 observational studies, metformin use is associated with reduced all-cause mortality in patients with CKD, CHF, or CLD with hepatic impairment, and with fewer heart failure readmissions in patients with CKD or CHF.
  
  
  CONCLUSIONS
  Strength of evidence was low, and data on multiple outcomes of interest were sparse. Available studies were observational and varied in follow-up duration.
  
  
  CONCLUSIONS
  Metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment is associated with improvements in key clinical outcomes. Our findings support the recent changes in metformin labeling.
  
  
  BACKGROUND
  U.S. Department of Veterans Affairs. (PROSPERO: CRD42016027708).
authors.affiliation: From Durham Veterans Affairs Medical Center and Duke University School of Medicine, Durham, North Carolina.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Crowley
authors.affiliation: From Durham Veterans Affairs Medical Center and Duke University School of Medicine, Durham, North Carolina.
authors.forename: Clarissa J
authors.initials: CJ
authors.lastname: Diamantidis
authors.affiliation: From Durham Veterans Affairs Medical Center and Duke University School of Medicine, Durham, North Carolina.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: McDuffie
authors.affiliation: From Durham Veterans Affairs Medical Center and Duke University School of Medicine, Durham, North Carolina.
authors.forename: C Blake
authors.initials: CB
authors.lastname: Cameron
authors.affiliation: From Durham Veterans Affairs Medical Center and Duke University School of Medicine, Durham, North Carolina.
authors.forename: John W
authors.initials: JW
authors.lastname: Stanifer
authors.affiliation: From Durham Veterans Affairs Medical Center and Duke University School of Medicine, Durham, North Carolina.
authors.forename: Clare K
authors.initials: CK
authors.lastname: Mock
authors.affiliation: From Durham Veterans Affairs Medical Center and Duke University School of Medicine, Durham, North Carolina.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Wang
authors.affiliation: From Durham Veterans Affairs Medical Center and Duke University School of Medicine, Durham, North Carolina.
authors.forename: Shuang
authors.initials: S
authors.lastname: Tang
authors.affiliation: From Durham Veterans Affairs Medical Center and Duke University School of Medicine, Durham, North Carolina.
authors.forename: Avishek
authors.initials: A
authors.lastname: Nagi
authors.affiliation: From Durham Veterans Affairs Medical Center and Duke University School of Medicine, Durham, North Carolina.
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Kosinski
authors.affiliation: From Durham Veterans Affairs Medical Center and Duke University School of Medicine, Durham, North Carolina.
authors.forename: John W
authors.initials: JW
authors.lastname: Williams
mesh_terms: D002423:Cause of Death; D002908:Chronic Disease; D000075202:Contraindications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy*; D006333:Heart Failure / Q000150:complications*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008107:Liver Diseases / Q000150:complications*; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin