Exenatide

Exenatide is an incretin mimetic. It improves glycaemic control via various glucoregulatory mechanisms, including glucose-dependent insulinotropism, suppression of inappropriately high glucagon levels, delayed gastric emptying and reduction of food intake. In three large, well designed, phase III trials in adults with type 2 diabetes mellitus and suboptimal glycaemic control despite treatment with metformin and/or a sulfonylurea, mean changes from baseline in glycosylated haemoglobin (HbA(1c)) significantly favoured subcutaneous exenatide 5 or 10microg twice daily over placebo after 30 weeks' treatment (primary endpoint). Relative to placebo, reductions from baseline in bodyweight were significantly greater with twice-daily exenatide 5microg (in two studies) or 10microg (in all three studies). Post hoc completer analyses revealed that the beneficial effects of exenatide on HbA(1c) and bodyweight were maintained for up to 82 weeks. Adjunctive therapy with subcutaneous exenatide 10microg twice daily improved glycaemic control to a similar extent as insulin glargine in patients with type 2 diabetes suboptimally controlled with metformin plus a sulfonylurea in a large, well designed, 26-week, phase III trial. Subcutaneous exenatide was generally well tolerated in patients with type 2 diabetes. The incidence of hypoglycaemia in patients receiving exenatide plus metformin was similar to that seen in placebo plus metformin recipients; however, in patients receiving a sulfonylurea (with or without metformin), the incidence of hypoglycaemia was numerically higher with exenatide than with placebo.