The Association Between Metformin Treatment and Outcomes in Type 2 Diabetes Mellitus Patients With Heart Failure With Preserved Ejection Fraction: A Retrospective Study.

Jianfang Wang,Yi Lu,Jia Wei,Tan Yuan,Xinjia Min,Zhejun Cai

doi:10.3389/fcvm.2021.648212

Abstract

Background: Metformin is the first-line antidiabetic medication for type 2 diabetes mellitus (T2DM). However, the association between metformin and outcomes in T2DM patients with heart failure with preserved ejection fraction (HFpEF) is still unknown. We aimed to explore the association between metformin and adverse outcome in T2DM patients with HFpEF.Methods: A total of 372 T2DM patients with HFpEF hospitalized from January 1, 2013, to December 31, 2017, were included in this retrospective cohort study. There were 113 and 259 subjects in metformin and non-metformin group, respectively. Subjects were followed up for all-cause mortality, cardiovascular death, all-cause hospitalization, and heart failure hospitalization.Results: The median follow-up period was 47 months. Eleven patients (2.49% per patient-year) in the metformin group and 56 patients (5.52% per patient-year) in the non-metformin group deceased during follow-up (P = 0.031). However, a multivariable Cox regression failed to show that metformin was an independent factor of all-cause mortality [HR (95% CI) = 0.682 (0.346–1.345); P = 0.269]. A subgroup analysis revealed a significant association between metformin and all-cause mortality in patients with a higher hemoglobin A1c (HbA1c) level (HbA1c ≥7%) [HR (95% CI) = 0.339 (0.117–0.997); P = 0.045]. The 4-year estimated number needed to treat (NNT) with metformin compared with non-metformin for all-cause mortality was 12 in all populations and 8 in the HbA1c ≥7% subgroup.Conclusions: Metformin was not independently associated with clinical outcomes in patients with T2DM and HFpEF, but was associated with lower all-cause mortality in the subgroup of patients with poor glycemic control. Prospective, randomized controlled trials are needed to further verify these findings.

Highlights

Heart failure with preserved ejection fraction (HFpEF) might be a heterogeneous syndrome of multiple discrete phenotypes and is prone to have multiple comorbidities, such as diabetes, hypertension, pulmonary disease, chronic kidney disease, and obesity [1], resulting in systemic and cardiac microvascular dysfunction [2, 3]
We performed a retrospective cohort study to investigate the association between metformin and this specific group of patients suffering from HFpEF with Type 2 diabetes mellitus (T2DM)
The median age was 71 years old, and 52.4% were male gender. 26.6% of the subjects were categorized as New York Heart Association (NYHA) class III-IV, and few patients have taken thiazolidinediones (TZD) or dipeptidyl peptidase-4 (DPP4) inhibitor

Summary

Introduction

Heart failure with preserved ejection fraction (HFpEF) might be a heterogeneous syndrome of multiple discrete phenotypes and is prone to have multiple comorbidities, such as diabetes, hypertension, pulmonary disease, chronic kidney disease, and obesity [1], resulting in systemic and cardiac microvascular dysfunction [2, 3]. Conventional therapies including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARB), beta-blockers, mineralocorticoid receptor antagonists (MRA) can improve the long-term outcomes of heart failure with reduced ejection fraction (HFrEF) [4]. These conventional medical therapies failed to reduce the risk of all-cause and cardiovascular death in HFpEF patients [5]. Metformin is the first-line antidiabetic medication for type 2 diabetes mellitus (T2DM). The association between metformin and outcomes in T2DM patients with heart failure with preserved ejection fraction (HFpEF) is still unknown. We aimed to explore the association between metformin and adverse outcome in T2DM patients with HFpEF

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