Metformin treatment in heart failure with preserved ejection fraction: A systematic review and meta-regression analysis
Open accessAbstract
BACKGROUND: Observational series suggest a mortality benefit from metformin in the heart failure (HF) population. However, the benefit of metformin in HF with preserved ejection fraction (HFpEF) has yet to be explored. We performed a systematic review and meta-analysis to identify whether variation in EF impacts mortality outcomes in HF patients treated with metformin. METHODS: MEDLINE and EMBASE were searched up to October 2019. Observational studies and randomised trials reporting mortality in HF patients and the proportion of patients with an EF > 50% at baseline were included. Other baseline variables were used to assess for heterogeneity in treatment outcomes between groups. Regression models were used to determine the interaction between metformin and subgroups on mortality. RESULTS: Four studies reported the proportion of patients with a preserved EF and were analysed. Metformin reduced mortality in both preserved or reduced EF after adjustment with HF therapies such as angiotensin converting enzyme inhibitors (ACEi) and beta-blockers (β = - 0.2 [95% CI - 0.3 to - 0.1], p = 0.02). Significantly greater protective effects were seen with EF > 50% (p = 0.003). Metformin treatment with insulin, ACEi and beta-blocker therapy were also shown to have a reduction in mortality (insulin p = 0.002; ACEi p < 0.001; beta-blocker p = 0.017), whereas female gender was associated with worse outcomes (p < 0.001). CONCLUSIONS: Metformin treatment is associated with a reduction in mortality in patients with HFpEF.
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Metformin treatment is associated with lower mortality in people with HFpEF and amelioration of cardiac functional parameters in patients with mild forms of HF, mainly HFpEF.
“These results might account for the lower mortality in metformin-treated people with HFpEF reported in a systematic review and meta-regression analysis, and for the amelioration of cardiac functional parameters possibly observed in patients with mild forms of HF, mainly HFpEF, no history of CV events, and after a long-time chronic treatment [159].”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [159]
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- Authors
- Halabi, A., Sen, J., Huynh, Q., & Marwick, T. H.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- Corresponding author
- Marwick, Thomas H.
- Venue
- Cardiovascular Diabetology
- Published
- 2020-08-05
- Volume
- 19
- Issue
- 1
- Pages
- 124-124
- ISSN
- 1475-2840 (ISSN-L)
- PMC
- PMC7409497
- OpenAlex
- W3047245556
- Cited by
- 93
- References
- 48
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 18 · 2023: 11 · 2022: 16 · 2021: 18 · 2020: 3
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cardiovascular Diabetology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UTAS Research Repository (acceptedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart rate and cardiovascular health
- Keywords
- metformin, heart failure with preserved ejection fraction, mortality, ejection fraction, insulin, ACE inhibitors, beta-blockers, sex differences, treatment interaction
- MeSH terms
- Aged, Blood Glucose, Diabetes Mellitus, Type 2, Female, Heart Failure, Humans, Hypoglycemic Agents, Male, Metformin, Risk Factors, Stroke Volume, Biomarkers, Randomized Controlled Trials as Topic, Ventricular Function, Left, Treatment Outcome, Risk Assessment, Observational Studies as Topic
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