Glucose homeostasis corresponds to the overall physiological, cellular, and molecular mechanisms which tightly maintain the glycaemia between ∼4.5 and ∼6 mM. The resulting blood glucose concentration is the consequence of a balance between the mechanisms that ensure the entry and the output of glucose in the blood. A dynamic balance needs hence to be perfectly achieved in order to maintain a physiological glycaemic concentration. Specialized cells from the intestine continuously detect changes in glucose concentration and send signals to peripheral tissues and the brain through the vagus nerve. The molecular mechanisms involved in glucose detection have not been perfectly defined but could resemble those from the insulin-secreting beta cells. The brain then integrates the enteric and circulating endocrine signals to generate a new signal towards peripheral tissues such as the pancreas, liver, muscles, and blood vessels. This metabolic reflex is called anticipatory since it allows the peripheral tissues to prepare for the adequate handling of nutrients. Diabetes is associated with an impaired anticipatory reflex, which hampers the proper detection of nutrients and leads to hyperglycaemic episodes. Recently, GLP-1-based therapies have demonstrated the improvement of glucose detection and their efficacy on glycaemic control. Although not yet fully demonstrated, GLP-1-based therapies regulate glucose sensors, which leads to the glycaemic improvement. Certainly other molecular targets could be identified to further generate new therapeutic strategies.