Hypoglycaemia is a feared and common unwanted effect of diabetes mellitus treated with insulin or sulfonylureas; it is the main reason insulin-treated individuals often fail to achieve the levels of glycaemic control necessary to prevent diabetic complications. Normal brain function depends on a continuous supply of glucose. If blood glucose falls below normal, interruption of this supply leads to cerebral dysfunction and, if not corrected, confusion and coma. Hypoglycaemia results chiefly from the inability of current glucose-lowering therapies to reproduce pancreatic β-cell physiology, leading to inappropriately high insulin concentrations between meals and at night.