Purpose: Insulin resistance plays a central role in the pathophysiology of metabolic syndrome (MS). Its cardiac deleterious effects are characterized by an increase in fibrous tissue that increases myocardial stiffness and contributes to subclinical left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction in patients with MS. In addition to lifestyle counseling (LC), metformin treatment may attenuate or even reverse diastolic dysfunction in these patients. This trial aims to evaluate if treating non-diabetic patients with MS and LVDD with metformin in addition to LC improves diastolic function and assess its impact in functional capacity and health-related quality of life (HRQoL).
Design: MET-DIME is a phase II prospective, randomized, open-label, blinded-endpoint trial with a scheduled follow-up of 24 months. Fifty-four patients (adults 40-65 years old with AHA/NHLBI criteria of MS and rest LVDD) will be randomized by minimization to LC only or LC plus metformin (target dose of 1,000 mg twice daily). The primary endpoint will be change in mean of early diastolic mitral annular velocity, an echocardiographic parameter highly correlated with myocardial fibrosis (serial measurements will be performed at 6, 12 and 24 months). The secondary endpoints will include change in diastolic parameters at rest; metabolic, inflammatory and remodeling biomarkers; functional capacity; adipose tissue volumes and HRQoL.
Conclusion: MET-DIME is a pragmatic trial designed to evaluate if adding metformin to the standard treatment of patients with MS improves diastolic dysfunction, assessing its impact in metabolic homeostasis, proinflammatory state, functional capacity and HRQoL.