Incretin hormones are gut derived peptides that augment the insulin releasing action of hyperglycaemia. In his seminal review, based on the 1978 Claude Bernard lecture, delivered at the European Association for the Study of Diabetes Meeting, Werner Creutzfeldt defined the term incretin as “an endocrine transmitter produced by the gastrointestinal tract which is: (a) released by nutrients, especially carbohydrates and (b) stimulates insulin secretion in the presence of glucose if exogenously infused in amounts not exceeding blood levels achieved after food ingestion”.¹ At that time, the best characterised incretin candidate was glucose dependent insulinotropic polypeptide (GIP), although there was evidence that GIP was not the only incretin.^1,3 An incretin role for GIP was established, along the lines of Creutzfeldt’s definition,¹ by intravenous infusion in healthy subjects, both alone and in combination with glucose, and demonstrating that the insulinotropic property of GIP was dependent on a permissive rise in blood glucose.² Subsequent experiments, performed under more physiological conditions, with plasma GIP and glucose concentrations mimicking the postprandial state, confirmed these observations.⁴ That relatively uncomplicated infusion experiments had the capacity to predict the physiological role of GIP with regard to its effects on insulin secretion is testimony to the fact that, metabolically speaking, GIP is apparently devoid of additional actions which have the potential to confound such experiments.⁵

The situation with glucagon-like peptide 1 (GLP-1) is far less straightforward. The GLP-1/glucose infusion experiment results in effects similar to those observed with GIP,⁶ and GLP-1, accordingly, fulfils the definition of an incretin hormone, as put forward by Creutzfeldt.¹ However, studies …