Exenatide Twice Daily: A Review of Its Use in the Management of Patients with Type 2 Diabetes Mellitus

Exenatide, administered subcutaneously twice daily (Byetta(A (R))), is a synthetic version of the natural peptide exendin-4, which is a glucagon-like peptide-1 (GLP-1) receptor agonist (incretin mimetic). Exenatide binds to the GLP-1 receptor with the same affinity as GLP-1, but has a much longer half-life, since it is not degraded by the enzyme dipeptidyl peptidase-4. Exenatide twice daily enhances glucose-dependent insulin secretion, suppresses inappropriately elevated glucagon secretion, slows gastric emptying and reduces caloric intake. In well-designed clinical trials, adjunctive subcutaneous exenatide 5 or 10 mu g twice daily for 16-52 weeks significantly and dose-dependently improved glycaemic control and reduced mean body weight compared with placebo in patients with type 2 diabetes inadequately controlled with oral antihyperglycaemic drugs (OADs) and/or basal insulin. The improvements in glycaemic control and reductions in body weight were stably maintained during long-term therapy (up to 3.5 years). The efficacy of adjunctive exenatide twice daily was generally similar to that of basal, prandial or biphasic insulin, sulfonylureas, rosiglitazone and lixisenatide, and less than that of liraglutide, taspoglutide or exenatide once weekly with respect to reductions in glycated haemoglobin. Exenatide twice daily was generally well tolerated; mild to moderate nausea and vomiting, which decreased with time on therapy, were the most common adverse events. In patients not receiving concomitant sulfonylureas or insulin, the incidence of hypoglycaemia was low; when it did occur, it was generally mild in severity. Thus, adjunctive exenatide twice daily is a valuable option in the treatment of type 2 diabetes inadequately controlled with OADs and/or basal insulin.