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Exenatide and liraglutide: different approaches to develop GLP-1 receptor agonists (incretin mimetics) – preclinical and clinical results

2009; Elsevier BV; Volume: 23; Issue: 4 Linguagem: Inglês

10.1016/j.beem.2009.03.008

1532-1908

Sten Madsbad,

Pancreatic function and diabetes

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.