The present invention includes methods and materials for manipulating the sense of satiety developed from the gastrointestinal transit of a substance in a mammal, whether the substance be a food or drug compound. The method involves administering a therapeutically effective amount, by a direct delivery route, of a pharmaceutically acceptable formulation comprising nutrients and pharmacological agents to the mammal's gastrointestinal tract. The present system is designed to maximize satiety feedback from normal intestinal sensors by small amounts of nutrients or nutrient derivatives, in essence, to “fool” body sensors that are not usually in contact with nutrients unless very large amounts are ingested.