leucine + metformin + sildenafil

The combination of leucine, metformin, and sildenafil (often referred to as NS-0200) is an investigational multi-component therapy studied primarily for the treatment of nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and obesity. Mechanistically, this combination targets key metabolic pathways involved in hepatic energy metabolism and inflammation. Leucine acts as an allosteric activator of sirtuin 1 (Sirt1), while metformin activates AMP-activated protein kinase (AMPK), and sildenafil enhances endothelial nitric oxide synthase (eNOS) activity via phosphodiesterase 5 inhibition. Together, these agents synergistically modulate the Sirt1–AMPK–eNOS pathway to increase hepatic fatty acid oxidation, reduce lipogenic gene expression, suppress inflammation, decrease fibrosis markers, and improve metabolic parameters such as body weight and triglyceride levels. Preclinical studies in mice demonstrated reversal of NAFLD/NASH features with this triple therapy; phase 2 clinical trials have shown dose-dependent reductions in body weight among obese subjects[1][3][4][5][7].

Brand names

Metformin Synergy Capsule

Other names

Sild-Met-LeuLeu-Met-Sil