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Post by sweedee79 on Feb 15, 2016 17:44:51 GMT -5
mnholdem ... I don't understand the connection of how the clamp study would produce results relevant to risk of DKA. I was hoping someone with more physiology/medical background might be able to explain. no medical expertise here... but if they compared injectable to Afrezza dose for dose in the trial... they aren't exactly the same.. in our experience a higher dose of Afrezza was required... Thing about Afrezza is you CAN give a higher dose because there is less risk of hypo and possibly aquired insulin resistance and the weight gain you get with injectable.. If you are on the correct dose of Afrezza I don't believe there is a higher risk of DKA. If your blood sugar does get away from you it builds up in the tissue and it takes a bit to get it back down. |
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Post by jerrys on Feb 15, 2016 22:23:40 GMT -5
mnholdem ... I don't understand the connection of how the clamp study would produce results relevant to risk of DKA. I was hoping someone with more physiology/medical background might be able to explain. Sure. I posted why Afrezza got the DKA, and am also hoping somebody with the expertise can explain. I do remember a long time ago that somebody wrote that it was because Afrezza had not proven in the FDA to be dose proportionate when administered at higher units. From the FDA briefing document:
"In the original dataset, using exposure adjusted incidence rates, DKA occurred 4.8 times more frequently in Afrezza TI treated patients than comparator treated patients (2.4 per 100 patient-years versus 0.4 per 100 patient years for Afrezza TI versus comparator). Review of the narratives for these cases suggested that most identified episodes were triggered by infections. (Narratives of interest are presented in the Appendices [section 5.4])."
"Reviewer’s comment: The Resubmission does not change the overall review findings for DKA, in that a higher incidence of DKA was observed among Afrezza treated patients. DKA and glycemic control are linked, and in light of the observed worse efficacy of Afrezza TI compared with insulin aspart as a prandial insulin for glycemic control in T1DM patients, the possibility exists that Afrezza TI contributed to this observed imbalance."
Those are the only references in the document that attempt to attempt to source the increased incidence of DKA.
Document is here:
FDA document
The narratives begin around page 100 and provide further information about specific cases. |
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Post by centralcoastinvestor on Feb 16, 2016 0:52:02 GMT -5
Sure. I posted why Afrezza got the DKA, and am also hoping somebody with the expertise can explain. I do remember a long time ago that somebody wrote that it was because Afrezza had not proven in the FDA to be dose proportionate when administered at higher units. From the FDA briefing document:
"In the original dataset, using exposure adjusted incidence rates, DKA occurred 4.8 times more frequently in Afrezza TI treated patients than comparator treated patients (2.4 per 100 patient-years versus 0.4 per 100 patient years for Afrezza TI versus comparator). Review of the narratives for these cases suggested that most identified episodes were triggered by infections. (Narratives of interest are presented in the Appendices [section 5.4])."
"Reviewer’s comment: The Resubmission does not change the overall review findings for DKA, in that a higher incidence of DKA was observed among Afrezza treated patients. DKA and glycemic control are linked, and in light of the observed worse efficacy of Afrezza TI compared with insulin aspart as a prandial insulin for glycemic control in T1DM patients, the possibility exists that Afrezza TI contributed to this observed imbalance."
Those are the only references in the document that attempt to attempt to source the increased incidence of DKA.
Document is here:
FDA document
The narratives begin around page 100 and provide further information about specific cases. When I read the results above about how Afrezza "caused" a more adverse reaction for DKA than comparator treated patients, I think of what Afrezzauser posted in one of his early blog pieces. See below: "In the future, if ever there was a test between 10 experienced Current Insulin users vs 10 experienced Afrezza users and the protocol was to do your best in managing your diabetes (for 1,2,3,6 or however many months) and tell us about your life before and after —I know the Current Insulin team wouldn’t stand a chance of winning in head to head competition against Afrezza. And I do mean this very seriously. In the trial, our data counted from day 1 and we competed against longtime Insulin users who knew what they were doing having years of experience. On the other hand, Afrezza was brand new, and we had limited instructions as to how to best utilize this medication and how it would work. We were all told “at the beginning of the meal” and that connotation is subject to varying degrees of interpretation for everyone. How could you expect great results when the Afrezza team was just learning how to “dial it in” and having to take baby steps with not much feedback or others experience to help you? From my current process, I know that for me when I check my blood sugar and if I’m over 120, then I’ll take Afrezza once I begin eating, but if I’m under that number, then I’ll wait for 15 minutes or so before I take my first dose. " The FDA trials were very unfair to Afrezza in so many ways. I wonder if the DKA results would have been the way they were if Afrezza patients could have had any flexibility in adjusting the doses. But then the FDA appeared to have it in for Afrezza anyway. Just read the transcripts from the FDA Advisory Committee paying close attention to what FDA staff said about Afrezza. |
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Post by agedhippie on Feb 16, 2016 8:27:07 GMT -5
The FDA trials were very unfair to Afrezza in so many ways. I wonder if the DKA results would have been the way they were if Afrezza patients could have had any flexibility in adjusting the doses. But then the FDA appeared to have it in for Afrezza anyway. Just read the transcripts from the FDA Advisory Committee paying close attention to what FDA staff said about Afrezza. DKA doesn't work like that. The exact time you take your insulin does not matter as long as there is insulin. The problems come when something like illness happens that pushes up your levels and you need a lot more insulin to manage it. My guess is that Afrezza just has a harder time being properly inhaled or absorbed at that time. A similar problem can occur with pumps where insulin may go bad or an occlusion blocks the tubing which is why a lot of people on pumps carry a pen for emergency use. The answer is probably the same for Afrezza and use a pen on those occasions as Sweedee did. |
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Post by sweedee79 on Feb 16, 2016 12:40:22 GMT -5
The FDA trials were very unfair to Afrezza in so many ways. I wonder if the DKA results would have been the way they were if Afrezza patients could have had any flexibility in adjusting the doses. But then the FDA appeared to have it in for Afrezza anyway. Just read the transcripts from the FDA Advisory Committee paying close attention to what FDA staff said about Afrezza. DKA doesn't work like that. The exact time you take your insulin does not matter as long as there is insulin. The problems come when something like illness happens that pushes up your levels and you need a lot more insulin to manage it. My guess is that Afrezza just has a harder time being properly inhaled or absorbed at that time. A similar problem can occur with pumps where insulin may go bad or an occlusion blocks the tubing which is why a lot of people on pumps carry a pen for emergency use. The answer is probably the same for Afrezza and use a pen on those occasions as Sweedee did. In my dad's case he wasn't on a high enough dose of Afrezza to begin with (he is T1). In our experience Afrezza is not the same dose for dose as injectable. The docs put him on the exact same dose as he was when on injectable. He needed a higher dose of Afrezza. They don't work the same way and it takes time to "dial it in" as mentioned. Problem is the docs wouldn't cooperate with us and refused to raise his dose. They didn't understand Afrezza and honestly didn't want to deal with learning about it either. My dad loved Afrezza, he felt so much better while on it and lost 24lbs and his blood pressure was better too.. his numbers however were not better on Afrezza because of the dosing issues. I honestly think that had he been on the right dose to begin with he wouldn't have had the problem with DKA.
Some of the early adopters are saying they can eat what they want using Afrezza. That is because they have docs who understand Afrezza and aren't afraid to raise the dose. You can take much more Afrezza without problems because it clears the body so fast and the risk of hypo is much less. My dad took larger doses at times and had no problems with hypo in the 6 months he was on Afrezza.
This is so frustrating for me. We have this amazing drug that mimics the pancreas and is a natural monomer insulin and people just don't get it. Because of the issues we had with insurance removing Afrezza from its formulary and the problems with docs my dad is now back on Novolog. He says he feels tired and lethargic on it and is gaining back his weight. He hates it.
I'm not sure about this trial because if they are comparing Afrezza to injectable dose for dose it isn't an accurate representation. The two drugs do not act the same. I do know that in my dads case that once his blood glucose got away from him Afrezza alone didn't work. We didn't try using injectable to bring it down, so I don't know if that would have worked better. He should have went to the doc but was too stubborn and just toughed it out until it got better. Docs may have possibly increased his basal insulin and prandial to bring it back down.
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