[New hypoglycemic agents in type 2 diabetes].
New treatments of type 2 diabetes have been developed, especially with the use of the properties of incretins, gastrointestinal hormones involved in glucose homeostasis. GLP-1 is responsible for most incretin effect with a rate that increases within minutes after meal intake, suggesting that its secretion is initially triggered by the combination of endocrine and nervous signals. The effects of GLP-1 on insulin secretion and glucagon are observed only at high glucose levels (glucose-dependent effects). In the type 2 diabetes, the incretin effect is altered due to reduced plasma concentrations of GLP-1, but its activity is intact. There are two innovative therapeutic approaches aimed to restore the incretin effect in patients with type 2 diabetes: the agonists of GLP-1 receptors administered subcutaneously that replace the deficiency of GLP-1; and the DPP-4 inhibitors that can prolong the life of endogenous GLP-1 by reducing activity of the enzyme DPP-4 that degrades GLP-1, molecules offering the advantage of oral administration. Their effectiveness on the glucose metabolism is around 0.5 to 1.1% and 0.8 to 1.5% in reduction in HbAlc for DPP-4 inhibitors and agonists of GLP-1 receptors, respectively. Moreover these latter have extra pancreatic effects, particularly by reducing gastric emptying and control of satiety, resulting in a weight loss of 1.6 to 3.8 kg. Their tolerance is generally good especially for the DPP-4 inhibitors, whereas agonists in GLP-1 receptor often cause nausea or vomiting at the initiation of the therapy. However their effectiveness and long-term safety need to be evaluated.
Guerci
Bruno
B
Université de Nancy I et service de diabétologie, maladies métaboliques et maladies de la nutrition, hôpital Jeanne-d'Arc, CHU de Nancy, 54201 Toul BP 90303. b.guerci@chu-nancy.fr
Halter
Charles
C
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004151:Dipeptides / Q000494:pharmacology / Q000627:therapeutic use; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069450:Liraglutide; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use; D014688:Venoms / Q000494:pharmacology / Q000627:therapeutic use; D000077597:Vildagliptin
D004151:Dipeptides; D007004:Hypoglycemic Agents; D009570:Nitriles; D010455:Peptides; D011719:Pyrazines; D011759:Pyrrolidines; D014230:Triazoles; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; C502994:saxagliptin; D000077270:Exenatide; D000077597:Vildagliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate