[From the discovery of incretin hormones to GIP / GLP-1 / glucagon double and triple agonists].

The concept of treating diabetes with gut hormones was proposed in the early days of endocrinology (1902), but was not put into practice until the early 2000s. The discovery of the incretin effect (potentiation of insulin secretion when glucose is taken orally compared to intravenously) led to the discovery of the two main gut hormones responsible for this effect: GIP and GLP-1. The reduction of the incretin effect is directly involved in the pathogenesis of type 2 diabetes, which has led to the development of a series of innovative therapies such as GLP-1 analogues, GLP-1 receptor agonists, GIP/GLP-1 co-agonists and GIP/GLP-1/glucagon tri-agonists. These therapies, with their potent hypoglycaemic and weight-lowering effects, promote optimal control of excess weight and hyperglycaemia, avoiding the escalation of treatment that was once considered inevitable.