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Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

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1. Metformin use is associated with reduced all-cause mortality in patients with chronic kidney disease, congestive heart failure, or chronic liver disease with hepatic impairment.

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2. In this systemic review, fewer heart failure readmissions were observed in patients with CKD or CHF that were treated with metformin.

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Evidence Rating Level: 1 (Excellent)

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Metformin is currently the suggested initial treatment for type 2 diabetes mellitus in the United States. In the past, the U.S. Food and Drug Administration (FDA did not recommend metformin for patients with chronic kidney disease (CKD), congestive heart failure (CHF), and/or chronic liver disease (CLD) with hepatic impairment. However, these recommendations were removed in 2006 due to the notion that the precautions were too restrictive. The purpose of this study, therefore, was to promote fully informed prescribing by synthesizing data addressing outcomes of metformin in these populations with historical contraindications. The authors concluded that metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment is associated with improvements in key clinical outcomes. There were several limitations to this study. First, not all outcomes of potential interest were evaluated. Additionally, strength of evidence was low and studies varied in follow-up duration. Overall, the results of this study support changes in metformin labeling to permit metformin use in additional patients with certain types of CHF, CKD, and CLD with hepatic impairment.

In-Depth [systematic review]:

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In this systematic review, articles were retrieved from MEDLINE, EMBASE, and International Pharmaceutical Abstracts from 1994 to 2015/16. 4910 citations were screened and 532 full-text articles were assessed. From these articles, 2 reviewers abstracted data and independently rated study quality and strength of evidence from 17 observational studies included in the analysis. Based on the available evidence from these studies, metformin therapy was found to be associated with reduced all-cause mortality among patients with moderate CKD, CHF, or CLD with impaired hepatic function. Specifically, 11 studies examined all-cause mortality. On meta-analysis, the relative chance of dying during follow-up was 22% lower for patients receiving metformin than for those that did not receive it (HR 0.78; CI 0.71 to 0.87, p = 0.003).

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