Metformin treatment is associated with improved outcome in patients with diabetes and advanced heart failure (HFrEF)

Abstract

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. 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. 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 more stable HF marked by lower BNP level (400 vs. 642 ng/l), better LV and RV function, lower mitral and tricuspid regurgitation severity, were using smaller doses of diuretics (all p < 0.05). Further, they had higher eGFR (69.23 vs. 63.34 ml/min/1.73 m²) and 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). MET treatment in patients with advanced HFrEF and DM is associated with improved outcome by mechanisms beyond the improvement of blood glucose control.

Figure 1

Metabolic profile. For Glucose and Hb1Ac, data are shown as mean ± SD, for HOMA-IR, Glucagon, GDF-15 and 3-hydroxybutyrate as median ± IQRs. For HOMA-IR, only patients without insulin treatment were evaluated (n = 196 DM MET-free, n = 61 DM MET-treated).

Figure 2

Event-free survival DM patients according DM treatment; MET-treated DM patients had significantly better survival, no significant difference in survival was observed among patients treated with other glucose-lowering agents.

Figure 3

Survival of MET-treated patients, propensity-score matched analysis. BMI body mass index, eGFR estimated glomerular filtration rate, LVEF left ventricle ejection fraction, RV right ventricle, BNP B-type natriuretic peptide, RAAi renin-angiotensin system inhibitors, ICD implantable cardioverter/defibrillator, CRT cardiac resynchronization, therapy, PAD peroral antidiabetics.