Exenatide once weekly
Exenatide has been developed in a sustained-release formulation for once-weekly subcutaneous administration. The exenatide molecules are encapsulated in injectable microspheres, which consist of a biodegradable medical polymer also used in other extended-release pharmaceuticals. These microspheres allow gradual drug delivery at a controlled rate by diffusion and erosion of the microspheres.
The clinical effects of exenatide once-weekly have been examined in the Diabetes therapy Utilisation: Researching changes in HbA1c weight and other factors Through Intervention with exenatide Once-weekly (DURATION) 1-6 trials. In all DURATION trials exenatide once-weekly lowered HbA1c and body weight significantly. The HbA1c reduction by exenatide once-weekly was up to 1.6%, and in most cases this reduction was greater or similar to that of the comparator. Overall a reduction in body weight by exenatide once-weekly was seen in the range of 2.1 to 2.6 kg. The DURATION-6 study comparing exenatide once-weekly with liraglutide once-daily is a 26-week head-to-head, open label, study including approximately 900 patients with type 2 diabetes who were inadequately controlled with diet and exercise in conjunction with metformin, SU, metformin plus a SU or metformin plus a thiazolidinedione. The study revealed that patients receiving exenatide once-weekly experienced a reduction in HbA1c of 1.3% compared to 1.5% for liraglutide. The mean change in weight from baseline to post treatment assessment was –2.7 kg for exenatide and –3.6 kg for liraglutide, with a mean difference of 0.9 kg overall. Thus, exenatide once-weekly did therefore not meet the pre-specified primary endpoint of non-inferiority to liraglutide with regards to HbA1c and body weight reductions. However, exenatide once-weekly did appear to be slightly better tolerated than liraglutide with less gastrointestinal side-effects (such as nausea and vomiting). Injection site reactions were observed more frequently in patients treated with exenatide once-weekly versus comparator treated patients (16 % versus range of 2-7 %) during the 6 month controlled phase of studies. These injection site reactions were generally mild and usually did not lead to withdrawal from studies. Most individual nodules were asymptomatic, did not interfere with study participation and resolved over 4 to 8 weeks.