Metformin in the management of patients with diabetes and advanced heart failure (HFrEF): a propensity score-matched analysis

Abstract

Background: The role of metformin (MET) in the treatment of patients with advanced HFrEF and type 2 diabetes mellitus (DM) is not firmly established. We studied the impact of MET on metabolic profile, quality of life (QoL) and survival in these patients. Methods: A total of 847 stable patients with advanced HFrEF (57.4± 11.3 years, 67.7% NYHA III/IV, LVEF 23.6± 5.8%) underwent clinical and laboratory evaluation and were prospectively followed for a median of 1126 (IQRs 410; 1781) days for occurrence of death, urgent heart transplantation or mechanical circulatory support implantation. Results: A subgroup of 380 patients (44.9%) had DM, 87 of DM patients (22.9%) were treated with MET. Despite worse insulin sensitivity and more severe DM (higher BMI, HbA1c, worse insulin resistance), MET-treated patients exhibited lower BNP, higher eGFR, better LV and RV function, less mitral and tricuspid regurgitation, were using smaller doses of diuretics (all p< 0.05) and had better QoL (MLHFQ: 36 vs. 48 points, p= 0.002). Compared to diabetics treated with other glucose-lowering agents, MET-treated patients had better event-free survival even after adjustment for BNP, BMI and eGFR (p= 0.035). Propensity score-matched analysis with 17 covariates yielded 81 pairs of patients and showed a significantly better survival for MET-treated subgroup (p= 0.01).Conclusion: MET treatment in patients with advanced HFrEF and DM is associated with better quality of life and improved outcome, by mechanisms beyond the improvement of blood glucose control. MET should stay among frontline drugs for treatment of DM in patients with HFrEF.

Anti-Diabetic Therapy, Heart Failure and Oxidative Stress: An Update

“…Moreover, whereas metformin was not independently associated with clinical outcomes in patients with type 2 DM and heart failure with preserved ejection fraction (HFpEF), it was associated with lower all-cause mortality in the subgroup of patients with poor glycemic control [ 80 ]. In a recent report dealing with diabetic patients with advanced heart failure with reduced ejection fraction (HFrEF), patients treated with metformin demonstrated better quality of life and improved outcomes compared with the patients not receiving metformin [ 81 ]. The authors concluded that metformin should stay among frontline drugs for treatment of HFrEF patients with DM [ 81 ].…”

“…In a recent report dealing with diabetic patients with advanced heart failure with reduced ejection fraction (HFrEF), patients treated with metformin demonstrated better quality of life and improved outcomes compared with the patients not receiving metformin [ 81 ]. The authors concluded that metformin should stay among frontline drugs for treatment of HFrEF patients with DM [ 81 ].…”

Biomarkers of RV dysfunction in HFrEF identified by direct tissue proteomics: extracellular proteins fibromodulin and fibulin-5

“…Right ventricular dysfunction (RVD) is a major complicating condition of heart failure (HF) with both preserved and reduced EF and is associated with poor prognosis (1)(2)(3). Although no specific RV dysfunction-targeted therapy is currently available, RV dysfunction is commonly present in advanced HF, and may herald clinical worsening with the need of intensification or therapy or timely indication to heart transplantation.…”