Exenatide extended-release; clinical trials, patient preference, and economic considerations

Type 2 diabetes remains an escalating problem worldwide, despite a range of treatments being available. The revelation that insulin secretion is under the control of a gut hormone, glucagon-like peptide 1, has led to a new paradigm in the management of type 2 diabetes, ie, use of medicines that directly stimulate or prolong the actions of endogenous glucagon-like peptide 1 at its receptors. Exenatide is an agonist at the glucagon-like peptide 1 receptor, and was initially developed as a subcutaneous medication twice daily (ExBID). Clinical trials with ExBID established a role for exenatide in the treatment of type 2 diabetes. Subsequently, exenatide once weekly (ExQW) was shown to have advantages over ExBID, and there is now more emphasis on the development of ExQW. ExQW alone reduces glycosylated hemoglobin (HbA(1c)) and body weight, and is well tolerated. ExQW has been compared with sitagliptin, pioglitazone, and metformin, and been shown to have a greater ability to reduce HbA(1c) than these other medicines. The only preparation of insulin with which ExQW has been compared is insulin glargine, and ExQW had some favorable properties in this comparison, notably causing weight loss compared with the weight gain on insulin glargine. ExQW has been compared with another glucagon-like peptide 1 receptor agonist, liraglutide, and was noninferior to liraglutide in reducing HbA(1c). The small amount of evidence available shows that subjects with type 2 diabetes prefer ExQW to ExBID, and that adherence is high in the clinical trial setting. Health care and economic modeling suggests that ExQW will reduce diabetic complications and be cost-effective, compared with other medications, in long-term use. Little is known about whether subjects with type 2 diabetes prefer ExQW to other medicines, and whether adherence is good with ExQW in practice. These important topics require further study.