Once-a-Month Dosing for Type 2s?

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By: Russell Phillips

A new glucagon-like peptide-1 (GLP-1) analog for type 2s that might require dosing only once a month is now in pre-clinical (animal) studies.  GLP-1, which increases insulin secretion from the pancreas, is a mighty helpful molecule, but with a sadly brief lifespan. It’s broken down in the body within minutes by the enzyme DPP-4.  That’s why drugs like Merck’s Januvia, a DPP-4 inhibitor, is effective: blocking DPP-4 subsequently increases the amount of GLP-1 in the system.  

Another way to tackle the problem of GLP-1’s vulnerability to DPP-4 is to make a GLP-1 analog: a molecule that works like GLP-1, but can hide from or resist DPP-4.  Byetta (exenatide), for example, is a GLP-1 analog that has been tweaked enough to stay in the system for awhile, but it still needs to be injected twice a day before meals.

The new GLP-1 analog (VRS-859), created by Versartis, is a recombinant fusion protein. That is, it’s made up of exenatide attached to XTEN. XTEN is a water-loving amino acid sequence that “covers” exenatide, hiding it from DPP-4 and protecting it from breakdown. This will, it is hoped, let the GLP-1 carry out its good works for a longer time, allowing for less frequent dosing and fewer side effects.

Sources:

biospace.com/

versartis.com

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