1 Cirius Therapeutics, Kalamazoo, MI, USA.
2 Cirius Therapeutics, San Diago, CA, USA.
Introduction: NASH and type 2 diabetes (T2D) are clinical definitions that overlap and result from metabolic dysfunction caused by over-nutrition relative to metabolic need. This volume details drug development programs aimed at specific NASH pathology with a focus on liver outcomes; this commentary suggests a metabolic approach that should not be overlooked based on a new understanding of insulin sensitizers.Areas covered: The overlap of NASHand T2D with respect to metabolic syndrome is discussed in the context of new understandings of insulin sensitizers. Adverse clinical outcomes in subjects with advanced NAFLD (e.g. NASH) and advanced metabolic dysfunction (e.g., T2D) are primarily due to cardiovascular issues. Clinical evidence suggests that insulin resistance and hyperinsulinemia predict adverse cardiovascular outcomes. NALFD/NASH significantly contributes to insulin resistance and hyperinsulinemia. A new insulin sensitizer that targets the newly identified mitochondrial pyruvate carrier could provide an approach.Expert opinion: A metabolic approach is needed for the treatment of NASH. Clinical studies are underway to determine whether a new insulin sensitizer that targets pyruvate metabolism can impact NASH, T2D, and cardiovascular disease. A broader view of metabolic disease may provide a more assessable way to track therapeutic benefit.