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Post by mango on Dec 15, 2021 13:19:19 GMT -5
Comparison of Pharmacokinetics and Pharmacodynamics of Inhaled Technosphere Insulin and Subcutaneous Insulin Lispro in the Treatment of Type 1 Diabetes MellitusClinical trial from 2015. Study just recently published by MannKind in November 2021. Lengthy paper, here’s just the abstract. Background This study was performed to satisfy a US Food and Drug Administration post-marketing requirement to compare the dose responses for Technosphere® Insulin (TI; MannKind Corporation, Westlake Village, CA, USA) and subcutaneous insulin lispro (LIS) across a wide range of doses. Objectives This single-center, open-label, randomized, cross-over study defined the pharmacokinetic/pharmacodynamic curves for inhaled TI vs subcutaneous LIS in persons with type 1 diabetes mellitus. Methods Each volunteer received six treatments while undergoing euglycemic clamps: three doses of TI (10, 30 and 120 U) and LIS (8, 30, and 90 U). Primary endpoint was area under the glucose infusion rate vs time curve from start of treatment administration to end of clamp. Key secondary endpoints included readouts of insulin exposure and timing of pharmacokinetic/pharmacodynamic profiles. Results Insulin exposure was more than dose proportional, increasing with dose1.08 for LIS and dose1.35 for TI. Time to reach 10% of the maximum glucose infusion rate was 7 to 15 min for TI vs 21 to 38 min for LIS. End of effect was dose dependent for both treatments, ranging from 2 to 6 h (TI) and 5 to 10 h (LIS). Glucose infusion rate exhibited saturation for both treatments. Technosphere Insulin produced a lesser total effect per unit insulin than LIS due to its faster absorption and correspondingly shorter duration of exposure. The difference was large enough to require significantly different doses to achieve the same total effect. Conclusions Technosphere Insulin has a considerably faster onset and shorter duration of action than LIS. Consequently, the overall effect of TI is smaller than that of LIS and unit-for-unit dose conversion is not appropriate. link.springer.com/article/10.1007%2Fs40262-021-01084-0
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Post by sportsrancho on Dec 15, 2021 13:41:04 GMT -5
Underdosed…. Underdosed….
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Post by sayhey24 on Dec 15, 2021 13:47:09 GMT -5
So this study was done in 2015 and has been available to Mannkind since then? When did Mike realize that the dosing on the label was not correct, this year? Of course if he read this board we have been saying this for years.
From the report "These data suggest that transitioning to TI from SC insulin on a unit-for-unit basis is not appropriate for the same reason that IV bolus insulin and SC insulin are not dosed on an equal-unit basis."
The biggest marketing mistake Al every made was calling the cartridges 4/8/12 units and not small, medium and large.
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Post by sportsrancho on Dec 15, 2021 14:22:17 GMT -5
Here in lays the most obvious problem, how are the doctors supposed to dose correctly if they don’t understand it. And it is not appropriate.
Same reason when Tom’s son got his first box of Afrezza and started to read the directions …Tom took it and threw it away. ( Being a Mannkind long of course he understood that the dosing instructions were far from correct. )
Same thing Bill’s been pounding the table about four years. That and getting people off Metformin!
So you have got this wonderful drug and it’s not being using it to its potential. Game changing, life changing potential.
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Post by olderteampt on Dec 15, 2021 15:47:08 GMT -5
It would almost make one think that Mike did not join MNKD to sell Afrezza but to stall it.
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Post by sportsrancho on Dec 15, 2021 16:52:04 GMT -5
From Bill~
“There’s something that has always been missing from this discussion: it always focuses on speed both onset and off. The implication is that Afrezza only effects while present in bloodstream. But there is a lingering effect from Afrezza that carries on well passed the point that the Afrezza has been metabolized away. Afrezza continues to control BG even many hours after out of system. How? We’re not sure, probably bc of effect on liver. The key point is that if one judges Afrezza only based upon Pk/PD profile one doesn’t get full story.”
This is just another fascinating aspect of the story
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Post by mango on Dec 15, 2021 17:14:35 GMT -5
From Bill~ “There’s something that has always been missing from this discussion: it always focuses on speed both onset and off. The implication is that Afrezza only effects while present in bloodstream. But there is a lingering effect from Afrezza that carries on well passed the point that the Afrezza has been metabolized away. Afrezza continues to control BG even many hours after out of system. How? We’re not sure, probably bc of effect on liver. The key point is that if one judges Afrezza only based upon Pk/PD profile one doesn’t get full story.” This is just another fascinating aspect of the story The affect on the liver is due to Afrezza restoring the first phase insulin response. |
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Post by sweedee79 on Dec 15, 2021 17:29:45 GMT -5
Yes, there is something really amazing about Afrezza.... My dad's blood pressure was better.. he had more energy... He felt better.. he lost weight.. it has to be that Afrezza is a more natural form of insulin and the body responds in a positive way..
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Post by Deleted on Dec 16, 2021 1:21:10 GMT -5
From Bill~ “There’s something that has always been missing from this discussion: it always focuses on speed both onset and off. The implication is that Afrezza only effects while present in bloodstream. But there is a lingering effect from Afrezza that carries on well passed the point that the Afrezza has been metabolized away. Afrezza continues to control BG even many hours after out of system. How? We’re not sure, probably bc of effect on liver. The key point is that if one judges Afrezza only based upon Pk/PD profile one doesn’t get full story.” This is just another fascinating aspect of the story This is probably why some Type 1's ONLY USE Afrezza and not a Basil Insulin. I have a couple of friends who have stopped using Lantus. They're having great control with Afrezza. |
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Post by mango on Dec 16, 2021 7:22:11 GMT -5
From Bill~ “There’s something that has always been missing from this discussion: it always focuses on speed both onset and off. The implication is that Afrezza only effects while present in bloodstream. But there is a lingering effect from Afrezza that carries on well passed the point that the Afrezza has been metabolized away. Afrezza continues to control BG even many hours after out of system. How? We’re not sure, probably bc of effect on liver. The key point is that if one judges Afrezza only based upon Pk/PD profile one doesn’t get full story.” This is just another fascinating aspect of the story This is probably why some Type 1's ONLY USE Afrezza and not a Basil Insulin. I have a couple of friends who have stopped using Lantus. They're having great control with Afrezza. That’s wild. I remember Sam Finta (T1D) talking about how he didn’t have his basal on a trip and only had Afrezza. Said he had great control the whole time with just Afrezza. You can do it because it works so fast and is out so quickly, there’s no stacking or long tail. It amazes me why any doctor would still be prescribing subq mealtime insulin. It’s an unsafe, antiquated, and barbaric treatment option now that we have Afrezza. |
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Post by mango on Dec 16, 2021 9:34:03 GMT -5
We have on our hands one of the greatest medical innovations of all time. Why has only 1% of people living with diabetes heard of Afrezza? Is CEO Mike Castagna reluctant to spread awareness due to the fact that they still have yet to get the dosing and timing correct and reflected on the label? People usually stop Afrezza because they don’t understand the dosing and timing. Without correct dosing and timing the Afrezza will not work properly. This is an enormous issue and hinderance to growth.
VDex has been preaching about this for years now.
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Post by oldfishtowner on Dec 16, 2021 12:17:45 GMT -5
This is probably why some Type 1's ONLY USE Afrezza and not a Basil Insulin. I have a couple of friends who have stopped using Lantus. They're having great control with Afrezza. That’s wild. I remember Sam Finta (T1D) talking about how he didn’t have his basal on a trip and only had Afrezza. Said he had great control the whole time with just Afrezza. You can do it because it works so fast and is out so quickly, there’s no stacking or long tail. It amazes me why any doctor would still be prescribing subq mealtime insulin. It’s an unsafe, antiquated, and barbaric treatment option now that we have Afrezza. As you well know, the issue here is that this is all anecdotal information and not based on data from formal clinical trials which is required in this age of "evidence based medicine."
While the pediatric trial may move some issues forward, like dosing, it is not going to establish Afrezza as a first line treatment for T2 or use for prediabetes/metabolic syndrome. That will require 1 or 2 more clinical trials, probably head-to-head against metformin, glp-1, etc. Nor will the pediatric trial eliminate the need for basil insulin for T1 as in Finta's example above.
And while the pediatric trial will be more aggressive with respect to dosing, as I interpret the protocol it does not provide for second doses. While there was a small study addressing this issue, it begs to be followed up by a larger trial.
And how about Afrezza's effects on vascular and heart health, liver, pancreas, blood pressure, cholesterol, triglycerides, glaucoma, amputations, etc.? We've heard some anecdotal evidence of some of this, but if the company is going to claim all the benefits of Afrezza that are possible, it has a lot of work ahead. Basically, after a decade we have hardly gotten off the block at the starting line.
I suppose the plan is that with the pediatric trial results in hand MNKD will be able to find another BP partner who will help move all this clinical work forward. I sure hope so, or that they find the money to do it themselves. And soon!
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Post by mango on Dec 16, 2021 12:37:30 GMT -5
That’s wild. I remember Sam Finta (T1D) talking about how he didn’t have his basal on a trip and only had Afrezza. Said he had great control the whole time with just Afrezza. You can do it because it works so fast and is out so quickly, there’s no stacking or long tail. It amazes me why any doctor would still be prescribing subq mealtime insulin. It’s an unsafe, antiquated, and barbaric treatment option now that we have Afrezza. As you well know, the issue here is that this is all anecdotal information and not based on data from formal clinical trials which is required in this age of "evidence based medicine."
While the pediatric trial may move some issues forward, like dosing, it is not going to establish Afrezza as a first line treatment for T2 or use for prediabetes/metabolic syndrome. That will require 1 or 2 more clinical trials, probably head-to-head against metformin, glp-1, etc. Nor will the pediatric trial eliminate the need for basil insulin for T1 as in Finta's example above.
And while the pediatric trial will be more aggressive with respect to dosing, as I interpret the protocol it does not provide for second doses. While there was a small study addressing this issue, it begs to be followed up by a larger trial.
And how about Afrezza's effects on vascular and heart health, liver, pancreas, blood pressure, cholesterol, triglycerides, glaucoma, amputations, etc.? We've heard some anecdotal evidence of some of this, but if the company is going to claim all the benefits of Afrezza that are possible, it has a lot of work ahead. Basically, after a decade we have hardly gotten off the block at the starting line.
I suppose the plan is that with the pediatric trial results in hand MNKD will be able to find another BP partner who will help move all this clinical work forward. I sure hope so, or that they find the money to do it themselves. And soon!
I was never suggested we try to replace basal insulin with Afrezza. Just commenting on the incredible versatility it holds and how safe it is. It’s pretty remarkable people with T1D are able to regulate their blood glucose with ease using only Afrezza. Why do we need more clinical trials to prove Afrezza has positive effects on other organs of the human body? We have very established scientific evidence and literature in great detail explaining the positive and negative benefits of tight control of blood glucose and dysregulation of blood glucose, the mechanisms of the first phase insulin response and the consequences of a diminished FPIR, and so on. We have numerous preclinical and clinical studies demonstrating Afrezza matches physiologic insulin and mimics the first phase, which in turn restores the homeostatic mechanisms involved, like signaling to the liver to shut off glucose production, and so on. We have clear evidence of this already. There is clear and abundant literature demonstrating the positive effects but short and long term of tight regulation of blood glucose and the consequences of it becoming dysregulated by a diminished or loss of the FPIR. To have numerous additional clinical trials demonstrating what we have already demonstrated and scientifically established would be redundant. Further, CGMs squash the “anecdotal” thing because it establishes itself as real world evidence. It’s repeatable and verifiable and thus considered evidence. |
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Post by sportsrancho on Dec 16, 2021 13:47:35 GMT -5
Mannkind does, Vdex doesn’t………
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Post by sayhey24 on Dec 16, 2021 18:11:17 GMT -5
That’s wild. I remember Sam Finta (T1D) talking about how he didn’t have his basal on a trip and only had Afrezza. Said he had great control the whole time with just Afrezza. You can do it because it works so fast and is out so quickly, there’s no stacking or long tail. It amazes me why any doctor would still be prescribing subq mealtime insulin. It’s an unsafe, antiquated, and barbaric treatment option now that we have Afrezza. As you well know, the issue here is that this is all anecdotal information and not based on data from formal clinical trials which is required in this age of "evidence based medicine."
While the pediatric trial may move some issues forward, like dosing, it is not going to establish Afrezza as a first line treatment for T2 or use for prediabetes/metabolic syndrome. That will require 1 or 2 more clinical trials, probably head-to-head against metformin, glp-1, etc. Nor will the pediatric trial eliminate the need for basil insulin for T1 as in Finta's example above.
And while the pediatric trial will be more aggressive with respect to dosing, as I interpret the protocol it does not provide for second doses. While there was a small study addressing this issue, it begs to be followed up by a larger trial.
And how about Afrezza's effects on vascular and heart health, liver, pancreas, blood pressure, cholesterol, triglycerides, glaucoma, amputations, etc.? We've heard some anecdotal evidence of some of this, but if the company is going to claim all the benefits of Afrezza that are possible, it has a lot of work ahead. Basically, after a decade we have hardly gotten off the block at the starting line.
I suppose the plan is that with the pediatric trial results in hand MNKD will be able to find another BP partner who will help move all this clinical work forward. I sure hope so, or that they find the money to do it themselves. And soon!
There are a zillion trials showing early use of insulin in T2s often stops and can even reverse diabetes progression. The big difference with afrezza and the other insulins used in these trials is the diabetic would have to try pretty hard to get a life threatening low. At some point someone will do another trial with afrezza which demonstrates this and in the conclusion of the study it will say we need another study. No matter what, you always need another study. Anyone who understands afrezza will not learn anything from such as study and who really thinks the ADA is going to change the SoC and make afrezza Step 1. Only an extremely well funded company with the correct technology and vision and who does not give a damn about the ADA or the current medical community can make this paradigm shift a reality. IMO, its going to happen but when it does its not going to be based on any study. VDex has been living this for years and seeing the results and as Mango said with CGMs we can see afrezza results in real time. The existing diabetes community is going to do everything possible the bury afrezza for as long as they can otherwise it will cost them B$$$'s both in diabetes treatments and other medical care when heart attacks dose dive and many fewer legs are cut off. Will the pediatric trials have an impact? Maybe. If afrezza really makes the lives of these little ones much better and safer and care of them easier, the Mama Bears are not going to give a damn about the ADA and will push change. Even still, its not going to impact the big market which is the T2s. |
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