Exenatide and liraglutide: different approaches to develop GLP-1 receptor agonists (incretin mimetics)--preclinical and clinical results.
The GLP-1 analogues exenatide and liraglutide stimulate insulin secretion and inhibit glucagon output in a glucose-dependent manner, slow gastric emptying and decrease appetite. The injectable glucagon-like peptide-1 (GLP-1) receptor agonist exenatide significantly improves glycaemic control, with average reductions in HbA1c of about 1.0% point, fasting plasma glucose of about 1.4 mmol l(-1), and causes a weight loss of approximately 2-3 kg after 30 weeks of treatment. The adverse effects are transient nausea and vomiting. The long-acting once-daily human GLP-1 receptor agonist liraglutide reduces HbA1c by about 1.0-2.0% point, weight by 1-3 kg and seems to have fewer gastrointestinal side effects than exenatide. The final place of the GLP-1 receptor agonists in the diabetes treatment algorithm will be clarified when we have long-term trials with cardiovascular end-points and data illustrating the effects on the progression of type 2 diabetes.
Madsbad
Sten
S
Department of Endocrinology, Hvidovre University Hospital, University of Copenhagen, Copenhagen N, Kettegaards Alle, Hvidovre, Denmark. sten.madsbad@hvh.regionh.dk
D019440:Anti-Obesity Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D017322:Clinical Trials, Phase II as Topic; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D000069450:Liraglutide; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D018027:Receptors, Glucagon / Q000819:agonists*; D014688:Venoms / Q000009:adverse effects / Q000627:therapeutic use*
D019440:Anti-Obesity Agents; D003692:Delayed-Action Preparations; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D000069450:Liraglutide; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C000593833:GLP1R protein, human; C517652:hemoglobin A1c protein, human