Bayliss and Starling identified the “hormone” by reference to a gut substance released into the blood stream and acting at a distance. The intestine was subsequently found to have a range of endocrine cells in its mucosa which release peptide hormones into the circulation. They are stimulated both by luminal nutriments and by their basal innervation from the submucous neural plexus. They have a variety of digestive functions, eg gastrin stimulates gastric acid secretion, motilin enhances gut contractility, cholecystokinin triggers gall bladder contraction and pancreatic enzyme secretion. Secretin stimulates neutralising alkaline juice flow from the pancreas. Secretin is a member of much larger peptide hormone family. Another gut hormone member is Glucagon-like peptide (GLP1) which enhances insulin release and has recently triggered a new class of therapeutics for diabetes. What took longer to identify was that several of these gut hormones had wider actions, for example affecting hedonistic brain circuits to regulate appetite.The only successful therapy for obesity is surgical. The roux en Y gastric bypass procedure, for example, results in life long weight reduction, improved life expectancy, halving of cancer rates and complete remission of diabetes, amongst several other beneficial effects. How does it work? Initially thought to produce malabsorption, it has now been shown to work mainly through reduction of appetite. How does it do this? Elevation of the satiety inducing gut hormones, oxyntomodulin, PYY and GLP1 are thought key. Could these hormones be administered therapeutically – a sort of medical bypass? The Imperial team thinks they could and has spent five years successfully developing hormone preparations that can be administered once a week and which result in long term appetite reduction.