Incretin Effect
The observation that oral glucose produces a greater insulin response than the same amount of glucose given intravenously. This enhanced response is mediated by incretin hormones (GLP-1 and GIP) released from the gut. The incretin effect is diminished in type 2 diabetes, which is one rationale for GLP-1 receptor agonist therapy.
Technical Context
The incretin effect is quantified by comparing insulin secretion during oral versus intravenous glucose administration at matched glycaemic levels (isoglycaemic clamp). The difference represents incretin-mediated insulin release. In healthy individuals, 50-70% of insulin secreted after an oral glucose load is attributable to incretins. In type 2 diabetes, this proportion is reduced to approximately 20-30% (the impaired incretin effect). This impairment results from both reduced GLP-1 secretion and pancreatic beta cell resistance to GIP. GLP-1 receptor agonists bypass the impaired incretin effect by providing supraphysiological GLP-1R activation, achieving insulin secretory responses that native incretin release cannot.