Exenatide.

Exenatide is the first in a new class of compounds, which possess similar activity to the naturally-occurring hormone glucagon-like peptide-1 (GLP-1). It mirrors many of the effects of GLP-1, improving glycaemic control through a combination of mechanisms, which include glucose-dependent stimulation of insulin secretion, suppression of glucagon secretion, slowing of gastric emptying and reduced appetite. Phase III clinical trials showed exenatide therapy for 30 weeks significantly reduced glycated haemoglobin, and fasting and postprandial plasma glucose compared with baseline when added to metformin and sulfonylureas or a combination of the two, with an average weight loss of approximately 2 kg. Exenatide can also be used in combination with thiazolidinediones and may be an alternative to insulin in patients requiring additional therapy. In patients with established Type 2 diabetes, control of both glycaemia and body weight are important to minimise the risk of future diabetes complications. Open-label extensions from these pivotal trials demonstrate that patients treated with exenatide for < or = 3 years sustained the reductions in glycaemic control achieved at 30 weeks and had a progressive reduction in body weight. Exenatide is generally well tolerated; nausea is the most commonly reported side effect, but can be significantly reduced when a target dose of exenatide is achieved in patients with gradual dose titration. Hypoglycaemia has been encountered in clinical trials of exenatide, especially on initiation of therapy with sulfonylureas (not with metformin). Exenatide may enable patients with Type 2 diabetes to improve glycaemic control and reduce or eliminate the risk of hypoglycaemia and weight gain.