Medscape: Effects of Exenatide (Byetta) on the Beta Cell

[warsurplus]

The presentation slides will not post here, so go to the link below to view the graphics:

http://www.medscape.com/viewarticle/544820_18

==================================================

Medscape CME:

Clinical Impact of Therapies Directed at Beta-cell Preservation

Robert R. Henry, MD

Preserving and Regenerating Beta Cells


Slide 23. GLP-1 Stimulates Beta-cell Regeneration and Mass
Going on to the preservation or regeneration of beta cells, you heard from Dr. Drucker about the potential of the GLP-1 analogs and the DPP-4 inhibitors to have beneficial effects on the beta cell by enhancing beta-cell neogenesis/proliferation, beta-cell hypertrophy, and the ability to inhibit apoptosis. So the GLP-1 analogs and the DPP-4 inhibitors have significant potential to not only maintain beta-cell function, but in fact, to possibly increase beta-cell secretion in people prone to developing diabetes, or those who have diabetes with loss of beta-cell function.


Slide 24. Effects of Exenatide on the Beta Cell
You heard earlier from Dr. Drucker about in vitro preclinical data on exenatide. Exenatide in cell cultures and in animals increases the expression of key beta-cell genes. It increases insulin synthesis and processing; it also increases beta-cell mass with increases in neogenesis and proliferation, and reductions in apoptosis. In humans to date, exenatide improves the insulin/proinsulin ratio consistent with improved insulin secretion. It restores first-phase insulin secretion (I will show you that in the next slide). It also augments insulin secretion at lower prevailing glucose concentrations.


Slide 25. Exenatide Restores First-Phase Insulin Secretion in Type 2 Diabetes
These are the effects of exenatide on first-phase insulin secretion; again, you saw preclinical data about this potential earlier. This is insulin secretion, shown on the vertical axis, to an IV bolus of glucose or an IV glucose tolerance test. There are 3 groups of subjects: healthy controls; untreated type 2 diabetics; and type 2 diabetics treated with exenatide. Following an IV bolus of glucose in nondiabetic subjects, there is normal first-phase insulin secretion, and then a second-phase tail appears. People with type 2 diabetes have lost their first-phase insulin secretion. However, following acute treatment with exenatide, you see a recovery of first-phase and second-phase insulin secretion -- a substantial improvement in the ability of the beta cell to respond to a standard IV glucose load.


Slide 26. Sustained A1C Reduction: Exenatide-Treated Patients
In the exenatide controlled trials -- the so-called Diabetes Management for Improving Glucose Outcomes (AMIGO) studies -- hemoglobin A1C was reduced by more than 1% over 26 weeks. As with glitazones, the open-label studies demonstrate sustained and durable glycemic control consistent with a persistent effect to sustaining insulin secretion, at least in these individuals with type 2 diabetes.


<snip>
...more...(on Liraglutide)
<snip>


Slide 28. Summary
To summarize, increased beta-cell function and mass will occur in response to increased beta-cell demand. There is a gradual decrease in beta-cell function and mass that may occur in individuals at high risk of developing type 2 diabetes. To prevent loss of beta-cell function and mass, beta-cell work must decrease and/or beta-cell stabilization or regeneration occurs.

Section 18 of 18

http://www.medscape.com/viewarticle/544820_18

Originally Posted by warsurplus

The presentation slides will not post here, so go to the link below to view the graphics:

http://www.medscape.com/viewarticle/544820_18

==================================================

Medscape CME:

Clinical Impact of Therapies Directed at Beta-cell Preservation

Robert R. Henry, MD

Preserving and Regenerating Beta Cells


Slide 23. GLP-1 Stimulates Beta-cell Regeneration and Mass
Going on to the preservation or regeneration of beta cells, you heard from Dr. Drucker about the potential of the GLP-1 analogs and the DPP-4 inhibitors to have beneficial effects on the beta cell by enhancing beta-cell neogenesis/proliferation, beta-cell hypertrophy, and the ability to inhibit apoptosis. So the GLP-1 analogs and the DPP-4 inhibitors have significant potential to not only maintain beta-cell function, but in fact, to possibly increase beta-cell secretion in people prone to developing diabetes, or those who have diabetes with loss of beta-cell function.


Slide 24. Effects of Exenatide on the Beta Cell
You heard earlier from Dr. Drucker about in vitro preclinical data on exenatide. Exenatide in cell cultures and in animals increases the expression of key beta-cell genes. It increases insulin synthesis and processing; it also increases beta-cell mass with increases in neogenesis and proliferation, and reductions in apoptosis. In humans to date, exenatide improves the insulin/proinsulin ratio consistent with improved insulin secretion. It restores first-phase insulin secretion (I will show you that in the next slide). It also augments insulin secretion at lower prevailing glucose concentrations.


Slide 25. Exenatide Restores First-Phase Insulin Secretion in Type 2 Diabetes
These are the effects of exenatide on first-phase insulin secretion; again, you saw preclinical data about this potential earlier. This is insulin secretion, shown on the vertical axis, to an IV bolus of glucose or an IV glucose tolerance test. There are 3 groups of subjects: healthy controls; untreated type 2 diabetics; and type 2 diabetics treated with exenatide. Following an IV bolus of glucose in nondiabetic subjects, there is normal first-phase insulin secretion, and then a second-phase tail appears. People with type 2 diabetes have lost their first-phase insulin secretion. However, following acute treatment with exenatide, you see a recovery of first-phase and second-phase insulin secretion -- a substantial improvement in the ability of the beta cell to respond to a standard IV glucose load.


Slide 26. Sustained A1C Reduction: Exenatide-Treated Patients
In the exenatide controlled trials -- the so-called Diabetes Management for Improving Glucose Outcomes (AMIGO) studies -- hemoglobin A1C was reduced by more than 1% over 26 weeks. As with glitazones, the open-label studies demonstrate sustained and durable glycemic control consistent with a persistent effect to sustaining insulin secretion, at least in these individuals with type 2 diabetes.


<snip>
...more...(on Liraglutide)
<snip>


Slide 28. Summary
To summarize, increased beta-cell function and mass will occur in response to increased beta-cell demand. There is a gradual decrease in beta-cell function and mass that may occur in individuals at high risk of developing type 2 diabetes. To prevent loss of beta-cell function and mass, beta-cell work must decrease and/or beta-cell stabilization or regeneration occurs.

Section 18 of 18

http://www.medscape.com/viewarticle/544820_18

Great for both Byetta and Dpp-4 inhibitors

Please tell me how this has anything to do with DPP-IV Inhibitors?

Originally Posted by Anonymous

Please tell me how this has anything to do with DPP-IV Inhibitors?

Read slide 23 dickhead...You dont think Merck has the same information? Its all coming sooner than you think.

Originally Posted by Anonymous

Read slide 23 dickhead...You dont think Merck has the same information? Its all coming sooner than you think.

it says "potential", dickhead!

do you know how to ascertain these results? you have to biopsy the pancreas of living subjects. the only way to do this is to remove it. or you can autopsy deceased patients.

in a nutshell, dickhead, there's never going to be any "real proof" with any of our current scientific methods.

go ahead and start telling your docs this because I will tear you down before you finish your sentence.

Originally Posted by Anonymous

it says "potential", dickhead!

do you know how to ascertain these results? you have to biopsy the pancreas of living subjects. the only way to do this is to remove it. or you can autopsy deceased patients.

in a nutshell, dickhead, there's never going to be any "real proof" with any of our current scientific methods.

go ahead and start telling your docs this because I will tear you down before you finish your sentence.

First its time to take your Zyprexa tough guy. Second when Merck releases "real proof" then i will speak to physicians about it. In case you lost track of time and didnt realize you were on your computer posting on Cafepharma, i was posting here not giving info in offices.

so when you're in your docs offices talking about your "weight neutral" effect, do you also mention that all the patients had diet and exercise counseling? do you mention that in the metformin arm of your clinical trials you had a small weight gain compared to placebo?

do give me your "real proof" crap. when it comes to beta cell function, there is NO WAY TO ASSESS IT! try having a high level scientific discussion with your endos about that.

then again I wouldn't want you to embarrass yourself and shit your pants because you can't say anything that's not been programmed into you by merck.