Metformin treatment in heart failure with preserved ejection fraction: a systematic review and meta-regression analysis

Abstract

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.

Effects of Metformin in Heart Failure: From Pathophysiological Rationale to Clinical Evidence

“…In HFpEF patients, metformin reduced long-term mortality following admission for acute HF and all-cause mortality in subjects with poor glycemic control [ 193 , 194 ]. A recent systematic review and meta-regression analysis confirmed a significant reduction of mortality in HFpEF by metformin, even after adjustment for HF therapies including β-blockers and angiotensin II inhibitor ACE-Is [ 195 ].…”

Role of Diabetes Mellitus in Heart Failure With Preserved Ejection Fraction: A Review Article

“…Several trials and meta-analyses have established that metformin, the only publicly available biguanide, is safe, efficacious, and is associated with improved cardiovascular outcomes in heart failure patients, making metformin first-line therapy for the treatment of DM in HFpEF patients [35][36][37][38]. A recent systematic review and meta-regression analysis suggest that the use of metformin in patients with HFpEF is associated with reduced mortality in HFpEF and HFrEF after adjustment for heart failure therapies such as angiotensin converting enzymes inhibitors (ACEI) and beta-blockers (BB).…”

Sodium-glucose cotransporter type 2 inhibitors: successful running after two hares

“…Лишь при применении метформина в лечении пациентов с сочетанием СД и ХСН (в т.ч. и с сохраненной ФВ ЛЖ) отмечалось снижение риска смерти [20,21]. У некоторых антидиабетических препаратов было выявлено даже негативное влияние на сердечно-сосудистые исходы.…”