Once-weekly drug therapy for diabetes

With the well-known fact that blood glucose levels (BGL) fluctuate moment-to-moment, and certainly day-by-day, it might be a bit surprising to hear that a diabetes medication could be developed that only needs once-weekly administration. But it's true -- Amylin and Eli Lilly have developed a once-weekly formulation of Byetta (exenatide), their GLP-1 analog drug for type 2 diabetes that presently requires injection twice-daily. The long-acting version of Byetta, nicknamed Byetta LAR (Byetta Longer-Acting Release), has completed phase III trials, and is presently undergoing review by the FDA; it is anticipated that it could be on the US market as soon as mid-year 2010.

Some study results about Byetta LAR are published: examples include:

* Exenatide once weekly for the treatment of type 2 diabetes. Exenatide once-weekly significantly improved glycemic control, resulted in patient weight loss, and was well tolerated in patients with T2DM. In a head-to-head clinical trial, exenatide once-weekly caused greater improvements in glycemic control and was better tolerated than exenatide twice-daily. (This review was written by Lilly staff.)

* Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. This study showed that "exenatide once weekly resulted in significantly greater improvements in glycaemic control than exenatide given twice a day, with no increased risk of hypoglycaemia and similar reductions in bodyweight."

* Improved treatment satisfaction and weight-related quality of life with exenatide once weekly or twice daily. Patients showed greater satisfaction with continuing treatment in the once-weekly group compared with the twice-daily group, and patients who switched from exenatide twice-daily to exenatide once-weekly reported further improvements.

* Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes.This phase II study showed that A1C, blood glucose, and weight all decreased, particularly on high dose Exenatide LAR.

Byetta LAR is not the only once-weekly diabetes drug in development: Roche is developing another drug, taspoglutide, which is in the same class as Byetta, and also would be injected once-weekly. This past week, Roche announced the results of a phase III trial (T-emerge 2 (subcutaneous weekly taspoglutide versus subcutaneous twice-daily exenatide, as add-on to metformin, a thiazolidinedione, or metformin and a thiazolidinedione), with 1189 T2DM patients): after 24 weeks of treatment, patients receiving the Roche drug had a greater decline in their BGL than those who had been given Byetta; the most frequently reported side effects from both drugs were nausea and vomiting. Results from other phase III studies on the new Roche drug are expected to become available soon, allowing Roche to proceed to filing for approval to sell their drug in the second half of 2010; if they do, they might have their product on the US market in 2011.