[New hypoglycemic agents in type 2 diabetes].
Keywords
Abstract
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.