Endocrine Abstracts

Since 2007 GLP-1 receptor agonists (GLP-1 analogues or incretins) are used for the treatment of type 2 diabetes mellitus. The mechanism of action includes stimulation of insulin secretion from pancreatic β-cells, inhibition of glucagon secretion from α-cells, induction of important β-cell specific genes (e.g. proinsulin, glucokinase and GLUT-2), reduction of postprandial glucose excursions by inhibition of gastric emptying and lowering of overall energy intake via central nervous signaling. In clinical trials they improve glucose control und induce weight-loss in the majority of patients without an increased risk for hypoglycemia. Recently long-acting GLP-1 agonists with a prolonged half-life for once daily or once weekly injection have been developed in order to fully exploit the therapeutic potential of GLP-1 and improve clinical effects. Side effects are similar compared to short-acting GLP-1 receptor agonists, GI-symptoms (nausea and vomiting) seem to occur less frequently. Much interest is focusing on the differentiation of molecules based on the half-life into long-acting versus short-acting GLP-1 receptor agonists, since it is increasingly apparent that exclusively short-acting molecules regulate glucose-metabolism also by inhibition of gastric emptying while long-acting molecules preferentially act by regulation of islet hormone levels. Thus, the perspective to combine GLP-1 based therapies with basal insulin may be an approach to effectively control both fasting and postprandial glycemia. In long-standing type 2 diabetes basal insulin may be preferentially combined with short-acting GLP-1 receptor agonists, while in early stages of type 2 diabetes long-acting GLP-1 molecules may be used as well. These combination therapies also help to improve individualized diabetes treatment. In order to evaluate the effect of GLP-1 based therapies on clinical endpoints, the results of long-term intervention trials are eagerly awaited.