|
|
Post by edvarney on May 19, 2016 18:01:39 GMT -5
This conversation of Afrezza and explanation by authors gives a terrific explanation that can easily be understood by any diabetic or medical expert on diabetes.. This is where Mike C. needs to be sure his field staff understand Afrezza titration vs competion; before they get into the field this summer.. I wish someone who oversees the proboard would take these posts on this subject and submit them directly to Mike C. for the sake of the new MNKD sales organization. The timing is perfect now.. to get all these questions answered for Afrezza new sales push..
God Bless.
|
|
|
|
Post by capnbob on May 19, 2016 19:46:15 GMT -5
FDA trial data seemed to show that Afrezza was faster in both PK and PD graphs...at least in this trial:
Do you notice how similar the header is to one of the new publications planned for release at ADA-2016?
Thhe problem is that the graph shown in your illustration was taken from data collected from healthy, non-diabetic volunteers while the graph utlized in the afrezza insert used data collected from actual type 1 diabetics. |
|
|
|
Post by capnbob on May 19, 2016 19:53:21 GMT -5
FDA trial data seemed to show that Afrezza was faster in both PK and PD graphs...at least in this trial: ...
Do you notice how similar the header is to one of the new publications planned for release at ADA-2016? I did wonder if that was why they redid the PK/PD study. The graph I had came from the prescribing information which is the one the doctors will look at. The study may be in order to change the graph used in the prescribing information and I expect since they are presenting the results at ADA 2016 they got what they were after and it looks more like the graph you posted. The studies used in the insert only compared three different doses of afrezza to a single dose of lispro -- I believe it was 8 or 10U. In any case, the new study compares three different doses of afrezza to the same three doses of lispro. |
|
|
|
Post by sweedee79 on May 19, 2016 22:43:09 GMT -5
My dads numbers were no different while he was on Afrezza... in fact they may have been inferior, dose for dose compared with Novolog (he wasn't on the correct dose of Afrezza)... however.... when you dial it in, Afrezza is far superior becuz because you are able to take more of it when you need to, due to the lesser risk of hypo. The patient has to learn what is right for them with the support of a knowledgeable doc... My dad said he felt so much better on Afrezza... he is now back to being lethargic and feeling tired on Novolog.. This says it all for me.. He wants Afrezza back really bad.. however as Mike C. said, Medicare part D will not be covering it for the rest of the year.. so we are waiting.. I just hope that something doesn't happen to my dad in the mean time.. I was worried about him tonight. I don't care what anyone says.. I have seen first hand what Afrezza is .. The body responds to it in a very positive way and IMO that is because it more closely mimics the pancreas and natural function.
|
|
|
|
Post by peppy on May 19, 2016 23:24:50 GMT -5
My dads numbers were no different while he was on Afrezza... in fact they may have been inferior, dose for dose compared with Novolog (he wasn't on the correct dose of Afrezza)... however.... when you dial it in, Afrezza is far superior becuz because you are able to take more of it when you need to, due to the lesser risk of hypo. The patient has to learn what is right for them with the support of a knowledgeable doc... My dad said he felt so much better on Afrezza... he is now back to being lethargic and feeling tired on Novolog.. This says it all for me.. He wants Afrezza back really bad.. however as Mike C. said, Medicare part D will not be covering it for the rest of the year.. so we are waiting.. I just hope that something doesn't happen to my dad in the mean time.. I was worried about him tonight. I don't care what anyone says.. I have seen first hand what Afrezza is .. The body responds to it in a very positive way and IMO that is because it more closely mimics the pancreas and natural function. Afrezzauser, Sam says the same. Paraphrasing, "he feels well."
You mention the contrast is lethargy. Just thinking that through.
The demon in me: So far, The medical establishment is willing to have people on a cheaper drug that secondarily causes lethargy, versus a non inferior insulin that people report gives them a feeling of wellness. I get the read from the medical community, we are doing this for you, why change, too unknown, stay with what you know. Some say they are afraid of lung delivery of a hormone. Proteins. Instead subq delivery is ok. dailymed.nlm.nih.gov/dailymed/archives/image.cfm?archiveid=168838&name=lantus-01.jpg screencast.com/t/f4fmb2N5G2VB
As a way aside, Mannkind has the patent for the oral buffered technosphere insulin. We have heard a lot about development projects, oral insulin would be huge. My concern there is the large dose of insulin required for oral delivery what kind of titration is involved there. If Mannkind could make a safe oral technosphere insulin, wouldn't the analogs for type two be changed to start type twos on insulin sooner. A safe oral insulin could take over the world. Why no words about this the shareholders meeting.
|
|
ben
Newbie
Posts: 12 
|
Post by ben on May 20, 2016 10:21:03 GMT -5
I have been thinking about why titration is not that important when using Afrezza. Feedback or corrections from any doctors, chemists or informed investor on the board would be appreciated. The following is my understanding of the process of insulin’s life in the body.
Insulin is typically degraded, by liver cells, about 71 minutes after its initial release into circulation. Afrezza is quickly released into circulation because it is an insulin monomer and is inhaled into the lungs. Novolog and Humalog are taken subcutaneously as insulin hexamers, so they are slowly released into circulation. This is an important point: the insulin from Novolog and Humalog degrades at about the same rate as the insulin from Afrezza, but because Novolog and Humalog are absorbed slower, there is a much longer tail from Novolog and Humalog.
Now think about how insulin affects glucose absorption. A cell’s insulin receptors, when an insulin molecule binds to it, leads to an increase in the glucose transporter (Glut4) molecules that induce glucose uptake. Once insulin binds to an insulin receptor, additional insulin has no further effect on that receptor.
With Afrezza, insulin is bound to many insulin receptors for about 71 minutes after the insulin has been absorbed through the lungs and into circulation. Since absorption is quick, the final 71 minutes starts soon after inhaling Afrezza. With Humalog and Novolog, the final 71 minutes happens much later because new insulin molecules are continually being absorbed for a much longer period.
While a meal is being digested, there is a steady influx of glucose entering the bloodstream. It takes some time for that glucose to absorb, even if many cells have active insulin receptors. If the rate of glucose is entering circulation is as high as the rate of cellular uptake, then there is no drop in the level of serum glucose. Depending on the glycemic index of the food that was consumed with the meal, glucose will continue to enter circulation for a specific period of time. If the time that glucose is enter the circulation is similar to the time that Afrezza is also still in circulation, then glucose levels will not drop too low.
If the dose of Afrezza was larger than needed, the excess insulin degrades quickly, before the meal is fully digested, without causing a low. With Novolog and Humalog, the excess insulin does not degrade as quickly, the excess insulin is problematic because it is still in circulation after the meal is digested.
My conclusion is that, for these reasons, a higher dose of Afrezza can be taken without causing hypoglycemia. If you need 1-4 units of Novolog, you can take 4 units of Afrezza without a problem; the excess insulin is degraded before it causes a problem.
From Wikipedia: “Once an insulin molecule has docked onto the receptor and effected its action, it may be released back into the extracellular environment or it may be degraded by the cell. Degradation normally involves endocytosis of the insulin-receptor complex followed by the action of insulin degrading enzyme. Most insulin molecules are degraded by liver cells. It has been estimated that a typical insulin molecule is finally degraded about 71 minutes after its initial release into circulation.”
BobW
A lot of good information here.... But, the bold underlined part is why it is not a good mealtime insulin for a lot of diabetics. First, if too much insulin is inhaled/taken, a Type I will go low. It's not a question of how fast it's removed, it's a question of what it does while there. Afrezza is going to promote sugar going from the blood into the cells. (There are a plethora of cells for sugar to go: liver first, then muscle second, and if those have all the glucose they need, then glucose is going to be forced into fat cells.) If too much is there, too much sugar will leave the blood and enter the cells. Further, and often overlooked, if it is gone in 71 minutes and the meal hasn't fully digested, sugar will be released during digestion into the blood with no insulin to get it into the cells which will result in hyperglycemia. Of course, another dose of Afrezza can then be taken to counter this, but dosing twice instead of once is not ideal. And, it requires more work. Test blood glucose --> eat --> inhale Afrezza --> test blood glucose --> inhale Afrezza is more complicated than Test BG --> inject insulin --> eat. The former likely results in tighter trends, but the later is easier. Now if they could show that Afrezza didn't force glucose into fat cells, they'd be onto something, but that is not my understanding of how it works. |
|
|
|
Post by peppy on May 20, 2016 10:31:11 GMT -5
I have been thinking about why titration is not that important when using Afrezza. Feedback or corrections from any doctors, chemists or informed investor on the board would be appreciated. The following is my understanding of the process of insulin’s life in the body.
Insulin is typically degraded, by liver cells, about 71 minutes after its initial release into circulation. Afrezza is quickly released into circulation because it is an insulin monomer and is inhaled into the lungs. Novolog and Humalog are taken subcutaneously as insulin hexamers, so they are slowly released into circulation. This is an important point: the insulin from Novolog and Humalog degrades at about the same rate as the insulin from Afrezza, but because Novolog and Humalog are absorbed slower, there is a much longer tail from Novolog and Humalog.
Now think about how insulin affects glucose absorption. A cell’s insulin receptors, when an insulin molecule binds to it, leads to an increase in the glucose transporter (Glut4) molecules that induce glucose uptake. Once insulin binds to an insulin receptor, additional insulin has no further effect on that receptor.
With Afrezza, insulin is bound to many insulin receptors for about 71 minutes after the insulin has been absorbed through the lungs and into circulation. Since absorption is quick, the final 71 minutes starts soon after inhaling Afrezza. With Humalog and Novolog, the final 71 minutes happens much later because new insulin molecules are continually being absorbed for a much longer period.
While a meal is being digested, there is a steady influx of glucose entering the bloodstream. It takes some time for that glucose to absorb, even if many cells have active insulin receptors. If the rate of glucose is entering circulation is as high as the rate of cellular uptake, then there is no drop in the level of serum glucose. Depending on the glycemic index of the food that was consumed with the meal, glucose will continue to enter circulation for a specific period of time. If the time that glucose is enter the circulation is similar to the time that Afrezza is also still in circulation, then glucose levels will not drop too low.
If the dose of Afrezza was larger than needed, the excess insulin degrades quickly, before the meal is fully digested, without causing a low. With Novolog and Humalog, the excess insulin does not degrade as quickly, the excess insulin is problematic because it is still in circulation after the meal is digested.
My conclusion is that, for these reasons, a higher dose of Afrezza can be taken without causing hypoglycemia. If you need 1-4 units of Novolog, you can take 4 units of Afrezza without a problem; the excess insulin is degraded before it causes a problem.
From Wikipedia: “Once an insulin molecule has docked onto the receptor and effected its action, it may be released back into the extracellular environment or it may be degraded by the cell. Degradation normally involves endocytosis of the insulin-receptor complex followed by the action of insulin degrading enzyme. Most insulin molecules are degraded by liver cells. It has been estimated that a typical insulin molecule is finally degraded about 71 minutes after its initial release into circulation.”
BobW
A lot of good information here.... But, the bold underlined part is why it is not a good mealtime insulin for a lot of diabetics. First, if too much insulin is inhaled/taken, a Type I will go low. It's not a question of how fast it's removed, it's a question of what it does while there. Afrezza is going to promote sugar going from the blood into the cells. (There are a plethora of cells for sugar to go: liver first, then muscle second, and if those have all the glucose they need, then glucose is going to be forced into fat cells.) If too much is there, too much sugar will leave the blood and enter the cells. Further, and often overlooked, if it is gone in 71 minutes and the meal hasn't fully digested, sugar will be released during digestion into the blood with no insulin to get it into the cells which will result in hyperglycemia. Of course, another dose of Afrezza can then be taken to counter this, but dosing twice instead of once is not ideal. And, it requires more work. Test blood glucose --> eat --> inhale Afrezza --> test blood glucose --> inhale Afrezza is more complicated than Test BG --> inject insulin --> eat. The former likely results in tighter trends, but the later is easier. Now if they could show that Afrezza didn't force glucose into fat cells, they'd be onto something, but that is not my understanding of how it works. what are you eating ben, a cow? |
|
ben
Newbie
Posts: 12
|
Post by ben on May 20, 2016 11:05:45 GMT -5
Ha. A cow wouldn't require much if any insulin.  But, no, normal everday meals. |
|
|
|
Post by mnholdem on May 20, 2016 11:25:32 GMT -5
Your post is really confusing ben. I understand you focusing on what happens if a patient takes too much Afrezza, but the consequences of taking too much RAA are much the same. Also, you are assuming that Afrezza will be degraded/gone in 71 minutes because of something you read in Wikipedia? Besides, that is talking about degradation at the cellular level, not depletion of insulin from the blood. The PK/PD data indicates that Afrezza hangs around for up to 2 hours, with the typical RAA in the 4-6 hour range. So it would appear that you are making assumptions here based on some questionable data. If patients who bolus with RAA insulin were to use your numbers, they wouldn't have to worry about stacking or having to snack whenever that long RAA tail causes hypo excursions a few hours after eating...which Afrezza users don't have to deal with, of course.
Good fortune to you.
|
|
|
|
Post by peppy on May 20, 2016 11:47:01 GMT -5
it is really as simple as this, running too low, eat an orange. eat a hard candy with some water drink some juice.
not rocket science.
|
|
|
|
Post by sportsrancho on May 20, 2016 12:38:25 GMT -5
it is really as simple as this, running too low, eat an orange. eat a hard candy with some water drink some juice. not rocket science. Peppy, this is about as unscientific as you can get. But I was at my clients birthday party. ( the one with the kids on Afrezza) Drinking and talking to the other women there. Besides his kids, Tom has gotten two other people on Afrezza. They are both men and are T2's. One guy had a really hard time getting his insurance to cover it. And he asked his doc if any other patients were on it. Again the doctor says no, you are the only one who asked. Makes me think this is patient driven? ...Back to the story, both wives of the two men on Afrezza told me that Afrezza has really changed their lives. The husbands were lethargic before taking Afrezza. Now after 8 months they feel like they did before they became T2's. And they both no longer have to take their Viagra! I had to laugh because this is probably the best kept secret, the men sure aren't going to say anything:-) Any scientific reason for this? Or do you think it's psychological? |
|
|
|
Post by peppy on May 20, 2016 12:53:17 GMT -5
it is really as simple as this, running too low, eat an orange. eat a hard candy with some water drink some juice. not rocket science. Peppy, this is about as unscientific as you can get. But I was at my clients birthday party. ( the one with the kids on Afrezza) Drinking and talking to the other women there. Besides his kids, Tom has gotten two other people on Afrezza. They are both men and are T2's. One guy had a really hard time getting his insurance to cover it. And he asked his doc if any other patients were on it. Again the doctor says no, you are the only one who asked. Makes me think this is patient driven? ...Back to the story, both wives of the two men on Afrezza told me that Afrezza has really changed their lives. The husbands were lethargic before taking Afrezza. Now after 8 months they feel like they did before they became T2's. And they both no longer have to take their Viagra! I had to laugh because this is probably the best kept secret, the men sure aren't going to say anything:-) Any scientific reason for this? Or do you think it's psychological? Blood vessel repair? Less leaking?  They do feel better on Afrezza.
|
|
|
|
Post by agedhippie on May 20, 2016 13:55:31 GMT -5
it is really as simple as this, running too low, eat an orange. eat a hard candy with some water drink some juice. not rocket science. And they both no longer have to take their Viagra! I had to laugh because this is probably the best kept secret, the men sure aren't going to say anything:-) Any scientific reason for this? Or do you think it's psychological? ED is a known diabetic complication. My endo uses it as an incentive with some of his more difficult patients... |
|
|
|
Post by mydogskip on May 20, 2016 17:53:46 GMT -5
And they both no longer have to take their Viagra! I had to laugh because this is probably the best kept secret, the men sure aren't going to say anything:-) Any scientific reason for this? Or do you think it's psychological? ED is a known diabetic complication. My endo uses it as an incentive with some of his more difficult patients... MNKD stock can't get it up either. |
|
|
|
Post by peppy on May 20, 2016 18:32:23 GMT -5
Peppy, this is about as unscientific as you can get. But I was at my clients birthday party. ( the one with the kids on Afrezza) Drinking and talking to the other women there. Besides his kids, Tom has gotten two other people on Afrezza. They are both men and are T2's. One guy had a really hard time getting his insurance to cover it. And he asked his doc if any other patients were on it. Again the doctor says no, you are the only one who asked. Makes me think this is patient driven? ...Back to the story, both wives of the two men on Afrezza told me that Afrezza has really changed their lives. The husbands were lethargic before taking Afrezza. Now after 8 months they feel like they did before they became T2's. And they both no longer have to take their Viagra! I had to laugh because this is probably the best kept secret, the men sure aren't going to say anything:-) Any scientific reason for this? Or do you think it's psychological? Blood vessel repair? Less leaking? They do feel better on Afrezza.
Better Nitric oxide supply and or transfer? Less cGMP degradation? I do not think it is psychology. 
Viagra stops the enzyme that PDE5, I think.
|
|
But, no, normal everday meals. 
