diabetes; either you could slow the degradation of endogenous GLP-1 using an inhibitor
to that enzyme, an inhibitor to DPP-4, Saxagliptin is an example of this, or you could
administer pharmacological GLP-1 that is resistant to DPP-4 degradation and therefore
has a longer half-life. Liraglutide which we will be discussing tomorrow is an example
of that mechanism. As I mentioned, Saxagliptin is a DPP-4 inhibitor. It’s administered
orally; the applicant is proposing once daily dosing. The only other approved DPP-4
inhibitor is Januvia or sitagliptin, which are also administered orally and also dosed once
daily and there are other DPP-4 inhibitors under development.
to meal but a preserved Insulin response to GLP-1 and this is the reason why GLP-1
based therapies are thought to have utility in this condition. The problem is it would be
very difficult to give endogenous GLP-1, or GLP-1 that’s identical to endogenous GLP-1,
to patients except perhaps with a continuous infusion. That’s because GLP-1 has a very
short half-life, on the order of less than two minutes. That’s because of rapid degradation
by a ubiquitous enzyme known as dipeptidyl-peptidase 4 (DPP-4).
Because it’s a protein-based therapy, it cannot be given orally so it’s administered
subcutaneously, and the applicant is proposing once daily dosing. The only other FDA
approved GLP-1 agonist is Byetta (exenatide), which is also administered subcutaneously
Currently, there are two approaches to GLP-1 based therapies for type 2
Liraglutide, which we are discussing tomorrow, is a GLP-1 agonist.
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GLP-1 stimulates Insulin release from the pancreas in a glucose-dependent manner,
and because it needs glucose around to have its effect the risk of hypoglycemia is
minimized when these types of agents are used by themselves. GLP-1 also slows gastric
emptying and reduces inappropriate post-meal glucagon release.
Interestingly, patients with type 2 diabetes have a reduced GLP-1 response