Metformin effects on cardiac parameters in non-diabetic Iraqi patients with heart failure and mid-range ejection fraction - a comparative two-arm parallel clinical study

Abstract

Heart failure (HF) remains a difficult challenge to the healthcare system, necessitating promoting interventions and multidrug management. Metformin, typically used to manage diabetes, has emerged as a promising intervention in the treatment of HF. This study aimed to assess the effect of adding metformin to the standard treatment of HF on cardiac parameters. This clinical study comprised 60 newly diagnosed HF patients randomly assigned to two groups: Group C received standard HF treatment, while Group M received standard HF treatment in addition to daily metformin (500 mg). After 3 months of treatment, group M showed a significantly higher ejection fraction (EF) compared to Group C (6.1% and 3.2%, respectively; p-value=0.023) and a reduction in the left ventricular end-diastolic pressure (LVEDD) (0.28, and 0.21 mm respectively; p-value=0.029). No significant differences were observed in the interventricular septal thickness (IVST) or left ventricular end-systolic pressure (LVESD). For cardiac markers, N-Terminal pro-BNP (NT-proBNP) showed the highest reduction in Group M compared to Group C (719.9 pg/ml and 271.9 pg/ml respectively; p-value=0.009). No significant changes were reported for soluble ST2. Metformin demonstrated cardiac protective effects by increasing EF and reducing NT-proBNP. Given its affordability and accessibility, metformin offers a valuable addition to the current HF treatment options. This positive effect may be attributed to mechanisms that enhance the impact of conventional HF treatments or vice versa.

Keywords: ACEI: Angiotensin-converting enzyme (ACE) inhibitor; AMPK: Adenosine Monophosphate-Activated Protein Kinase; ARNI: Angiotensin receptor/Neprilysin inhibitor; BMI: Body Mass Index; EF: Ejection Fraction; Echocardiography; HF: Heart Failure; HFmrEF: Heart Failure with mid-range Ejection Fraction; HbA1C: Glycated Hemoglobin A1C; Heart failure; IVST: Interventricular Septal Thickness; LV: Left Ventricle; LVEDD: Left Ventricular End Diastolic Diameter; LVESD: Left Ventricular End Systolic Diameter; Metformin; N-terminal proBNP; NT-proBNP: N Terminal pro-brain natriuretic peptide; ST2: soluble suppression of tumorigenicity 2; T2DM: Type 2 Diabetes mellitus.