Based on extensive studies which employed exogenous native FGF21 in both rodent and non-human primate disease models [1], [19], [21], [24], [29], [33]–[37] and these additional results obtained with LY2405319, there is a compelling rationale to evaluate the potential therapeutic utility of FGF21-based molecules in patients with cardio-metabolic disorders which include metabolic syndrome, obesity, Type 2 diabetes, hepatic steatosis, and atherosclerosis [38]. Here, FGF21 is linked to obesity due to melanocortin 4 receptor deficiency.