[Glucagon-like peptide-1 (GLP-1), new target for the treatment of type 2 diabetes]

Glucagon-like peptide-1 (GLP-1) is a gut hormone secreted in response to the ingestion of a meal. It exerts various favourable metabolic effects among which a glucose-dependent stimulation of insulin secretion, an inhibition of glucagon secretion, a slow down of gastric emptying, and a central anorectic effect. In rodents, a protective effect, or even a trophic effect, on B cell has also been reported. Interestingly, GLP-1 secretion is decreased in patients with type 2 diabetes. This observation stimulated the pharmaceutical research with the aim of restoring appropriate GLP-1 circulating levels able to exert the numerous positive effects of the hormone. One of the main objectives was to solve the problem due to the very short half-life of GLP-1. We here briefly describe the main two proposed approaches : ether to subcutaneously inject an incretinomimetic agent closed to GLP-1 (exenatide) or a long-acting GLP-1 analogue (liraglutide), both being partially resistant to the action of dipeptidylpeptidase-IV (DPP-IV), either to orally administer a selective DPP-IV inhibitor, an enzyme metabolising endogenous GLP-1 (sitagliptin, vildagliptin, .... These new drugs offer the advantage of improving blood glucose control of type 2 diabetic patients, without inducing severe hypoglycaemia and without promoting weight gain (instead a weight reduction is generally observed). These agents should occupy a key place in the overall pharmacological strategy of type 2 diabetes in a near future, especially if the additional favourable effects on B cells are confirmed in clinical practice.