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Metformin Appears Safe for Heart Failure, Other Diabetes Co-Morbidities

by U.S. Medicine

June 30, 2017

DURHAM, NC – While recent changes to the U.S. Food and Drug Administration boxed warning for metformin are likely to increase the common diabetes drug’s use in patients with historical contraindications or precautions, prescribers are cautioned to understand the clinical outcomes of metformin use in these populations, including patients with heart failure.

A review published in Annals of Internal Medicine discussed possible 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.1

To do that, Durham, NC, VAMC and Duke University researchers analyzed studies from MEDLINE (via PubMed) from January 1994 to September 2016, and Cochrane Library, EMBASE, and International Pharmaceutical Abstracts from January 1994 to November 2015. Included were 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.

Two reviewers abstracted data and independently rated study quality and strength of evidence, according to the report.

Results indicated that, based on 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.

Last year, the FDA announced it was requiring labeling changes regarding the recommendations for metformin-containing medicines for diabetes to expand the common drug’s usage in certain patients with reduced kidney function. The labeling previously had strong recommendations against use of metformin in some patients with renal issues.

Study authors of the VA-funded review cautioned that strength of evidence was low, and too little data was available on multiple outcomes of interest. In addition, available studies were observational and varied in follow-up duration.

“Metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment is associated with improvements in key clinical outcomes,” the researchers concluded. “Our findings support the recent changes in metformin labeling.”

  1. Crowley MJ, Diamantidis CJ, McDuffie JR, Cameron CB, Stanifer JW, Mock CK,

Wang X, Tang S, Nagi A, Kosinski AS, Williams JW Jr. Clinical Outcomes of Metformin Use in Populations With Chronic Kidney Disease, Congestive Heart Failure, or Chronic Liver Disease: A Systematic Review. Ann Intern Med. 2017 Feb 7;166(3):191-200. doi: 10.7326/M16-1901. Epub 2017 Jan 3. Review. PubMed PMID: 28055049; PubMed Central PMCID: PMC5293600.


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