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diabetes; either you could slow the degradation of endogenous GLP-1 using an inhibitor

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to that enzyme, an inhibitor to DPP-4, Saxagliptin is an example of this, or you could

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administer pharmacological GLP-1 that is resistant to DPP-4 degradation and therefore

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has a longer half-life. Liraglutide which we will be discussing tomorrow is an example

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of that mechanism. As I mentioned, Saxagliptin is a DPP-4 inhibitor. It’s administered

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orally; the applicant is proposing once daily dosing. The only other approved DPP-4

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inhibitor is Januvia or sitagliptin, which are also administered orally and also dosed once

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daily and there are other DPP-4 inhibitors under development.

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to meal but a preserved Insulin response to GLP-1 and this is the reason why GLP-1

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based therapies are thought to have utility in this condition. The problem is it would be

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very difficult to give endogenous GLP-1, or GLP-1 that’s identical to endogenous GLP-1,

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to patients except perhaps with a continuous infusion. That’s because GLP-1 has a very

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short half-life, on the order of less than two minutes. That’s because of rapid degradation

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by a ubiquitous enzyme known as dipeptidyl-peptidase 4 (DPP-4).

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Because it’s a protein-based therapy, it cannot be given orally so it’s administered

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subcutaneously, and the applicant is proposing once daily dosing. The only other FDA

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approved GLP-1 agonist is Byetta (exenatide), which is also administered subcutaneously

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Currently, there are two approaches to GLP-1 based therapies for type 2

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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,

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and because it needs glucose around to have its effect the risk of hypoglycemia is

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minimized when these types of agents are used by themselves. GLP-1 also slows gastric

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emptying and reduces inappropriate post-meal glucagon release.

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Interestingly, patients with type 2 diabetes have a reduced GLP-1 response

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