[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.
Scheen
A J
AJ
Université de Liege, Service de Diabétologie, Nutrition et Maladies métaboliques et Unité de Pharmacologie clinique, CHU Liège, Belgique.
D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D001066:Appetite / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000077270:Exenatide; D005746:Gastric Emptying / Q000502:physiology; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000502:physiology / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D000069450:Liraglutide; D009570:Nitriles / Q000627:therapeutic use; D010455:Peptides / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D011759:Pyrrolidines / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use; D014688:Venoms / Q000627:therapeutic use; D000077597:Vildagliptin
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D009570:Nitriles; D010455:Peptides; D011719:Pyrazines; D011759:Pyrrolidines; D014230:Triazoles; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077270:Exenatide; D000077597:Vildagliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate