Liraglutide, a once-daily human GLP-1 analogue

Abstract

Glucagon-like peptide-1 (GLP-1) is an incretin hormone physiologically playing a role in glucose homeostasis, together with the partner incretin, glucose dependent insulinotropic peptide (GIP). Active concentrations of this hormone are not maintained for long because of its very rapid degradation and elimination. The effects of the hormone are of potential therapeutic value in type 2 diabetes; therefore, analogues of GLP-1 have been developed that are characterised by a prolonged circulating half-life relative to the naturally occurring hormone. One such long-acting analogue is liraglutide. The effects of liraglutide are maintained over 24 h, allowing once-daily dosing. Liraglutide provides all of the beneficial actions of endogenous GLP-1: glucose-dependent stimulation of insulin secretion, glucagon suppression, deceleration of gastric emptying, appetite suppression/weight loss and, in animal models, inhibition of β-cell apoptosis and promotion of β-cell regeneration. Because liraglutide stimulates insulin secretion and suppresses glucagon secretion only when blood glucose levels are elevated, the risk of treatment-associated hypoglycaemia is low. In clinical studies, liraglutide substantially lowered fasting and postprandial glucose concentrations, with an overall reduction in haemoglobin A1c of up to 1-2%. In some studies, liraglutide has decreased several biomarkers of cardiovascular risk and lowered triglyceride levels significantly. Side effects most commonly are gastrointestinal symptoms; they are usually mild to moderate and resolve over time. Long-term clinical trials are needed to assess whether the effects of liraglutide on the β cell translate into a durable improvement in β-cell function and mass in patients with type 2 diabetes and, if so, whether this will slow or halt disease progression and help prevent complications.Br J Diabetes Vasc Dis, 2008; 8 (Suppl 2): S26—S33