Exenatide

Abstract

▴ 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 10μg 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 5 μg (in two studies) or 10μg (in all three studies). ▴ Post hoc completer analyses revealed that the beneficial effects of exenatide on HbA_1c and body-weight were maintained for up to 82 weeks. ▴ Adjunctive therapy with subcutaneous exenatide 10μg 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.