For decades, extensive research has aimed to clarify the role of pancreas and gut-derived peptide hormones in the regulation of glucose homeostasis and feeding behavior. Among these are the beta-cell hormone amylin and the intestinal L cell hormone glucagon-like peptide-1 (GLP-1). They exhibit distinct and yet several similar physiological actions including suppression of food intake, postprandial glucagon secretion, and gastric emptying-altogether lowering plasma glucose and body weight. These actions have been clinically exploited by the development of amylin and GLP-1 hormone analogs now used for treatment of diabetes and obesity. This review will outline the physiology and pharmacological potential of amylin and GLP-1, respectively, and focus on innovative peptide drug development leading to drugs acting on two or more distinct receptors, such as an amylin and GLP-1 peptide hybrid, potentially producing a more effective treatment strategy to combat the rapidly increasing global obesity.