Glucagon and the thyroid hormone T3 lower lipid levels and promote weight loss, making these hormones exceptional candidates for treating metabolic disease; however, as monotherapies, they also have deleterious effects that limit their therapeutic potential. Thyroid hormone T3 lowers serum cholesterol and lipoprotein levels and increases adipose tissue energy expenditure, but these beneficial attributes are accompanied by increased food intake, an elevated heart rate, cardiac hypertrophy, muscle wasting, and bone loss. Glucagon also displays productive activities, such as the lowering of triglycerides and promoting weight loss, but these are accompanied by increases in liver gluconeogenesis leading to detrimental hyperglycemia