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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.

Item Type:	Refereed Article
Keywords:	diabetes mellitus, metformin, heart failure, ejection fraction
Research Division:	Biomedical and Clinical Sciences
Research Group:	Cardiovascular medicine and haematology
Research Field:	Cardiology (incl. cardiovascular diseases)
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Marwick, TH (Professor Tom Marwick)
ID Code:	140456
Year Published:	2020
Web of Science® Times Cited:	26
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2020-08-19
Last Modified:	2022-08-25
Downloads:	17 View Download Statistics