Promising Results Reported for Once Monthly GLP-1 Agonist; Bydureon Inches Closer to Possible Approval
For type 2 patients, the use of GLP-1 agonists (such as Victoza and Byetta) can often lead to significant improvements in blood glucose control and weight loss with little risk for hypoglycemia. Animal studies have even suggested that these therapies possess a protective effect on beta cells (potentially slowing or halting beta cell death) and on the cardiovascular system (possibly reducing the risk for heart attacks, stroke, heart disease, etc.). Despite these benefits, the need to administer GLP-1 agonists by injection (twice daily injections with Byetta and once daily injections with Victoza) is sometimes a notable barrier to beginning the therapy and adhering to it. Fortunately, several companies have begun developing longer-acting GLP-1 agonists in an effort to reduce the number of injections.
Two such companies are Amylin and Eli Lilly, the makers of Byetta, which are again teaming up to develop once-weekly and once-monthly GLP-1 formulations. Bydureon, the once-weekly formulation, has already successfully finished phase 3 human studies, demonstrating an ability to provide greater blood glucose control (determined by A1c) and similar weight loss as Byetta but with reduced rates for nausea and vomiting (common side effects associated with GLP-1 agonists). The companies recently announced that a small trial (called a thorough QT study) that will examine Bydureon’s effect on the heart was initiated in February and will be completed by the end of this year. If all goes according to plan, Bydureon may be approved in the US by mid-2012 (for more information on Bydureon, please see the Learning Curve in diaTribe issue # 26).
Amylin and Eli Lilly have also recently reported positive results from a small phase 2 study that compared their once-monthly GLP-1 formulation (referred to as exenatide once-monthly) to Bydureon. Like Bydureon, exenatide once-monthly is composed of exenatide, the active ingredient found in Byetta, and microscopic spheres that slowly release the drug into the bloodstream. Unlike Bydureon, however, exenatide once-monthly does not require reconstitution (mixing the drug into solution) before administration, a feature that should improve ease of use. In the 20-week study, participants receiving exenatide once-monthly achieved similar improvements in blood glucose control (average A1c reductions between 1.3% and 1.5%) as those receiving Bydureon (average A1c reduction of 1.5%). Both drugs also appeared to be safe and tolerable with no minor or major hypoglycemic events reported and with headache and nausea (for exenatide once-monthly) and headache and diarrhea (Bydureon) listed as the most common adverse events associated the respective therapies. Although promising, these results will need to be confirmed in larger and longer phase 3 trials, meaning that exenatide once-monthly will not likely become available for at least three years. Yet the prospect of a once-monthly drug for type 2 diabetes is certainly exciting, and we look forward to keeping you updated as we hear more news in months and years to come. --BK