Clinical Outcomes of Metformin Use in Populations With Chronic Kidney Disease, Congestive Heart Failure, or Chronic Liver Disease: A Systematic Review
Open accessAbstract
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. PURPOSE: 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. DATA SOURCES: MEDLINE (via PubMed) from January 1994 to September 2016, and Cochrane Library, EMBASE, and International Pharmaceutical Abstracts from January 1994 to November 2015. STUDY SELECTION: 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. DATA EXTRACTION: 2 reviewers abstracted data and independently rated study quality and strength of evidence. DATA SYNTHESIS: 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. LIMITATIONS: Strength of evidence was low, and data on multiple outcomes of interest were sparse. Available studies were observational and varied in follow-up duration. CONCLUSION: 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. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs. (PROSPERO: CRD42016027708).
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Diabetic patients with liver, kidney and heart diseases who did not receive metformin could have benefited from its use with reduced hospitalization and mortality.
“Recently, it was evident that diabetic patients with liver, kidney and heart diseases, who did not receive metformin could have benefitted from its use with reduced hospitalization and mortality (Crowley et al. 2017).”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Crowley et al. 2017
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- Authors
- Crowley, M. J., Diamantidis, C. J., McDuffie, J. R., Cameron, C. B., Stanifer, J. W., Mock, C. K., Wang, X., Tang, S., Nagi, A., Kosinski, A. S., & Williams, J. W.
- Affiliations
- Duke University (US)
- From Durham Veterans Affairs Medical Center and Duke University School of Medicine, Durham, North Carolina.
- ORCID
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2017-02-07
- Volume
- 166
- Issue
- 3
- Pages
- 191-200
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- PMC
- PMC5293600
- OpenAlex
- W2570191103
- Cited by
- 287
- References
- 45
- Citations by year
- 2026: 10 · 2025: 22 · 2024: 25 · 2023: 23 · 2022: 31 · 2021: 40 · 2020: 48 · 2019: 35 · 2018: 28 · 2017: 24 · 2016: 1
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (ESP Project #09-009)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- metformin, chronic kidney disease, congestive heart failure, chronic liver disease, liver dysfunction, type 2 diabetes, all-cause mortality, major adverse cardiovascular events, heart failure readmission, FDA boxed warning, drug contraindications
- MeSH terms
- Contraindications, Cause of Death, Chronic Disease, Diabetes Mellitus, Type 2, Heart Failure, Humans, Hypoglycemia, Hypoglycemic Agents, Liver Diseases, Metformin, Treatment Outcome, Renal Insufficiency, Chronic
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