INS and metabolic disease: Administration of leptin with insulin, amylin, cholecystokinin and GLP-1 analog to enhance their effects on the animals with experimental metabolic disorders and in clinical trials [186–193]; administration of bromocryptine with insulin, metformin, glipizide and pioglitazone to synergize their effects in patients with T2DM and in experimental diabetes [219,222,225,228]; co-administration of MC4R agonists and GLP-1 analogs to improve insulin sensitivity and energy expenditure in experimental animals much more effectively than monotherapy [319]