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Post by longliner on Jun 16, 2020 1:21:30 GMT -5
The only reason you've given for not using Afrezza that I could remember was this, from May 2016 - four years ago. Still waiting?
"All of this said - I would like to move to Afrezza but right now I am going to hold back and see if any lung issues materialize. I want someone else to be the guinea pig. There have been the trials and a years use, but I want bigger numbers of users for a couple of years before I move."
I thought the primary reason I gave was that I don't see it as necessary for me. My A1c is 6.3 with minimal hypos and that's good enough for me. If it ain't broke don't fix it. Also still waiting for the users to turn up rather than the numbers there are now... Silly me.........and I thought you were waiting for the vampire squid to issue its first upgrade.
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Post by agedhippie on Jun 16, 2020 8:00:22 GMT -5
I thought the primary reason I gave was that I don't see it as necessary for me. My A1c is 6.3 with minimal hypos and that's good enough for me. If it ain't broke don't fix it. Also still waiting for the users to turn up rather than the numbers there are now... 6.3 is highest endpoint for pre diabetic. Pre diabetes is 5.7 to 6.3. My latest A1C is 5.3 which equate to non diabetic after being on Afrezza for 4++ years. You lose the argument in perpetuity. I think we are having different arguments then. Mine is that I am perfectly happy with an A1c of 6.3 and as such see no reason to change. I think your argument is that I could do a lot better, but that ignores the fact that I don't believe it matters enough which means the whole argument goes nowhere. This is a general problem - if people think change is more effort than it's worth, whether they are right to wrong, then that change is not going to happen. This happens in all medicine, not just diabetes. If I was trying to sell Afrezza I wouldn't talk about how low the A1c can go, I would talk about moving from a 12 to a 9 because people can visualize that happening and it seems both possible and desirable. If you have an A1c of 12 I would think that an A1c of 5.7 seems impossible (I am not talking about what is medically possible, this is purely about perception).
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Post by agedhippie on Jun 16, 2020 8:05:02 GMT -5
... My Father in law was suffering from severe lows every time he took prandial insulin, since starting Afrezza, he hasn’t been low one time. The first night on Afrezza was miserable for him, because he kept waiting to go low, but it never happened. Stayed up all night for nothing. He was afraid to go to sleep at night because he lives alone, and didn’t feel confident enough to hook up his CGM. He was so afraid of going low, that he wasn’t injecting his RAA until after his meal, and his blood sugar was rising. His endos failed him, he didn’t understand why it was important to try and time the rise, and inject before he started his meal, which was compounding his lows. Now all he has to do is keep his BG from going high, and it makes more sense to him because he can take his insulin when he starts his meal, or even after like he was doing with the RAA’s. There is literally no comparison between the two insulin products, they are two completely different products, and Afrezza is beyond superior. I’ve got a brain, I saw it with my own eyes. ✌🏻😎 This is why I would hate to see Afrezza off the market, I want diabetics to have as many options as possible. RAA was obviously failing for your father-in-law and Afrezza fixed the problem. In his position I would do exactly the same as him.
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Post by agedhippie on Jun 16, 2020 9:03:17 GMT -5
I thought the primary reason I gave was that I don't see it as necessary for me. My A1c is 6.3 with minimal hypos and that's good enough for me. If it ain't broke don't fix it. Also still waiting for the users to turn up rather than the numbers there are now... Silly me.........and I thought you were waiting for the vampire squid to issue its first upgrade. Mmmm. Vampire calamari.
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Post by shawnonafrezza on Jun 16, 2020 9:13:41 GMT -5
With CGMs there is no need for an additional comparator arm. The comparator arm are the same PWDs. With CGMs you know exactly how they were performing prior to the introduction of the changed medication - in this case afrezza. In this study - prior to afrezza you had these PWDs on the CGM and RAA. In this study they took 25 people, measured their baseline with the RAA and CGM and then switched them to afrezza. If the previous Dexcom studies are correct these PWDs should have already seen some A1c benefit prior to afrezza since they were already using the CGM with the RAA. IMO, going forward this is the way to do studies as you don't have the variable of different people being compared. Instead you have the exact same person. The failure of this study was measuring TIR during sleeping hours. This needs to be factored out. This study included it which made it a flawed study. The big question is what do the AGPs look like which are not included in the abstract. Concerning the second dose with a T2 you and Shawn are wrong. In the case of a T2 there is a lot of leeway and its really up to the T2 how good they want their numbers to be. If a T2 like Joey wants great numbers looking at his CGM 1hr after eating and second dosing is no big deal. They want to do it. If they miss a second dose every once in a while - oh well. For the T2 who has high A1cs and is being put on a cocktail of poisons like SGLT2s, etc. one puff of afrezza during meal should significantly improve their numbers even if they don't second dose. Afrezza provides the T2 choice and should be used prior to TZDs, SGLT2 and GLP1s and of course metformin as its creates the greatest harm due to the lost time in addressing the problem. Per the abstract - Patients were titrated from pre-meal insulin plus basal insulin to inhaled insulin plus basal insulin over 2 weeks and followed for 14 weeks. At Week 14, mean (±SE) times spent above (>180 mg/dL; -1.7±3.2 mins; P=0.60), in (70 180 mg/dL; -1.2±2.6 mins; P=0.65), and below (<70 mg/dL; +2.9±2.5 mins; P=0.26) glycemic goal range were not significantly different from baseline. However, A1c significantly decreased from baseline at Week 14 (-0.76%±0.18; P=0.0002). At Week 14, Quality of Life (QoL) Total score did not significantly change from baseline (+0.19±0.13; P=0.15). However, Useful (+0.46±0.20; P=0.03), Freeing (+0.92±0.24; P=0.0008), and Difficult ( 0.68±0.28; P=0.02) QoL subdomains significantly improved from baseline at Week 14 Why would they include TIR during sleeping hours for a mealtime insulin product. I’m a fricken dumb old Bass Player and even I can see how that would water down the results of the trial. Dilution is the solution I guess. 🤓 That's actually kind of a nuanced answer and I can answer it with another question or two. How long does the meal digest for and how close did the patient eat before falling asleep? In an ideal world basal keeps sugars flat and any deviation from that is the responsibility of the bolus insulin. That's why I would include it. I wouldn't include it because most diabetics don't have a flat basal anyway.
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Post by rockstarrick on Jun 16, 2020 10:03:57 GMT -5
Why would they include TIR during sleeping hours for a mealtime insulin product. I’m a fricken dumb old Bass Player and even I can see how that would water down the results of the trial. Dilution is the solution I guess. 🤓 That's actually kind of a nuanced answer and I can answer it with another question or two. How long does the meal digest for and how close did the patient eat before falling asleep? In an ideal world basal keeps sugars flat and any deviation from that is the responsibility of the bolus insulin. That's why I would include it. I wouldn't include it because most diabetics don't have a flat basal anyway. This is why I say RAA’s and Afrezza are two completely different products. If Afrezza is out of the system in around 90 minutes, I’d say for most, it’s gone before sleep. RAA’s stay in the system for over 4 hours, so maybe it makes sense here. I just don’t believe that Afrezza is present and doing anything related to TIR after about 90 minutes, it’s the basal insulin that keeps a PWD in range overnight, if Afrezza was still doing anything PWD would go low at night like they do with RAA’s.
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Post by shawnonafrezza on Jun 16, 2020 10:10:36 GMT -5
That's actually kind of a nuanced answer and I can answer it with another question or two. How long does the meal digest for and how close did the patient eat before falling asleep? In an ideal world basal keeps sugars flat and any deviation from that is the responsibility of the bolus insulin. That's why I would include it. I wouldn't include it because most diabetics don't have a flat basal anyway. This is why I say RAA’s and Afrezza are two completely different products. If Afrezza is out of the system in around 90 minutes, I’d say for most, it’s gone before sleep. RAA’s stay in the system for over 4 hours, so maybe it makes sense here. I just don’t believe that Afrezza is present and doing anything related to TIR after about 90 minutes, it’s the basal insulin that keeps a PWD in range overnight, if Afrezza was still doing anything PWD would go low at night like they do with RAA’s. Correct, but a meal is not done digesting after 90 minutes so does Afrezza just get a pass? If you ran a trial like that the outcome could only prove better TIR for the 90 minutes post meal. That would also remove the tail from RAA. You'd have to prove basal was set right and then let the bolus do what it is. Unfortunately, unless the study somehow allows ad lib bolusing for highs Afrezza would struggle there. It'd have to be written in a way where if BGL is > X and last Afrezza dose was more than 90 minutes ago the pt boluses. That is what people who are successful do but not what any trial has done.
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Post by sayhey24 on Jun 16, 2020 10:35:00 GMT -5
This is why I say RAA’s and Afrezza are two completely different products. If Afrezza is out of the system in around 90 minutes, I’d say for most, it’s gone before sleep. RAA’s stay in the system for over 4 hours, so maybe it makes sense here. I just don’t believe that Afrezza is present and doing anything related to TIR after about 90 minutes, it’s the basal insulin that keeps a PWD in range overnight, if Afrezza was still doing anything PWD would go low at night like they do with RAA’s. Correct, but a meal is not done digesting after 90 minutes so does Afrezza just get a pass? If you ran a trial like that the outcome could only prove better TIR for the 90 minutes post meal. That would also remove the tail from RAA. You'd have to prove basal was set right and then let the bolus do what it is. Unfortunately, unless the study somehow allows ad lib bolusing for highs Afrezza would struggle there. It'd have to be written in a way where if BGL is > X and last Afrezza dose was more than 90 minutes ago the pt boluses. That is what people who are successful do but not what any trial has done. A TIR study for a prandial insulin should only include those hours the PWD is awake and can act to adjust their BG - for example 7am to 10pm. When the PWD is sleeping they are a victim of whats in their system be it the basal or the basal and RAA tail. The goal of the RAA is to mimic pancreatic release but because of absorption limitations non current do. While some want to argue the tail is an advantage for slow digesting food it is not as the ability to second dose as necessary provides greater control and predictability. However not including the sleeping hours in a TIR study would be a huge disadvantage for the RAA's as would reducing the TIR upper limit to 150-160. This study allowed second dosing of afrezza and actually encouraged it but trying to convince existing RAA users to second dose an insulin even afrezza in a 14 week period was a huge challenge. I have not seen the AGP from this study but I would like to.
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Post by rockstarrick on Jun 16, 2020 10:46:59 GMT -5
... My Father in law was suffering from severe lows every time he took prandial insulin, since starting Afrezza, he hasn’t been low one time. The first night on Afrezza was miserable for him, because he kept waiting to go low, but it never happened. Stayed up all night for nothing. He was afraid to go to sleep at night because he lives alone, and didn’t feel confident enough to hook up his CGM. He was so afraid of going low, that he wasn’t injecting his RAA until after his meal, and his blood sugar was rising. His endos failed him, he didn’t understand why it was important to try and time the rise, and inject before he started his meal, which was compounding his lows. Now all he has to do is keep his BG from going high, and it makes more sense to him because he can take his insulin when he starts his meal, or even after like he was doing with the RAA’s. There is literally no comparison between the two insulin products, they are two completely different products, and Afrezza is beyond superior. I’ve got a brain, I saw it with my own eyes. ✌🏻😎 This is why I would hate to see Afrezza off the market, I want diabetics to have as many options as possible. RAA was obviously failing for your father-in-law and Afrezza fixed the problem. In his position I would do exactly the same as him. Couldn’t agree more. He’s a man of very few words, a big time corn farmer his whole life, hit the fields early and worked late 7 days a week. He just isn’t the type of guy that’s going to spend a lot of time worrying or learning about diabetes. I was a little shocked when I had the opportunity to watch that CGM for about 5 days before the Afrezza arrived, he was in a constant battle every time he ate. I totally understand that his experience isn’t representative or typical of other PWD using RAA’s, because of when and how he was dosing, he would take 10 units after the meal, then another 5 a little later. He was definitely compounding his lows because he didn’t understand how the insulin worked. He’s still dialing in the Afrezza, and there were things he didn’t like when he first started, but just the fact that he doesn’t go low is a big win for him. I’m really glad I took the time to drive over there and get him set up, he would’ve never taken the time to figure out how to get the G6 sensor inserted, the receiver calibrated and paired, and the transmitter correctly attached to the sensor, plus all the general set up, time, date, sensor and transmitter serial numbers. The G6 didn’t come with the receiver, I had to pay $400 to have one overnighted, I guess they thought he already had one, or maybe wanted him to update a G5, but he’s never had a CGM that I know of. It was worth it to me, just having that visual of both products really helped him decide which insulin he wanted to use. He was hesitant to change, like you said most would be. I think it was the best 4000 miles I’ve ever driven, it felt really great to help him out, because he really needed the help. ✌🏻😎
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Post by shawnonafrezza on Jun 16, 2020 10:56:12 GMT -5
Correct, but a meal is not done digesting after 90 minutes so does Afrezza just get a pass? If you ran a trial like that the outcome could only prove better TIR for the 90 minutes post meal. That would also remove the tail from RAA. You'd have to prove basal was set right and then let the bolus do what it is. Unfortunately, unless the study somehow allows ad lib bolusing for highs Afrezza would struggle there. It'd have to be written in a way where if BGL is > X and last Afrezza dose was more than 90 minutes ago the pt boluses. That is what people who are successful do but not what any trial has done. A TIR study for a prandial insulin should only include those hours the PWD is awake and can act to adjust their BG - for example 7am to 10pm. When the PWD is sleeping they are a victim of whats in their system be it the basal or the basal and RAA tail. The goal of the RAA is to mimic pancreatic release but because of absorption limitations non current do. While some want to argue the tail is an advantage for slow digesting food it is not as the ability to second dose as necessary provides greater control and predictability. However not including the sleeping hours in a TIR study would be a huge disadvantage for the RAA's as would reducing the TIR upper limit to 150-160. This study allowed second dosing of afrezza and actually encouraged it but trying to convince existing RAA users to second dose an insulin even afrezza in a 14 week period was a huge challenge. I have not seen the AGP from this study but I would like to. I agree with all you're saying but we have slightly different conclusions. If the goal is to mimic the pancreas then a second dose is needed. If that is the case, and we want a phase 2 response and the user is asleep you either have to accept that they will not get it or have them wake up and fix it. The normal pancreas doesn't care if you're asleep so if that is the benchmark then the trial can't care if you're asleep. This gets even harder from the point of view that other companies like tandem and medtronic are touting TIR, including sleep-time, with RAA. That's why I think the focus for Afrezza should be immediate, 90 minute post meal, results. If you can't get the users to follow up dose then you have to push for what you can without a doubt get and there it should be obvious. I also think that needs to come out sooner rather than later because each evolution of closed loop systems will push harder and harder and post meal spikes which mean the focus of Afrezza has to really target the users that don't want to be connected to a pump (see what Companion Medial is doing for that).
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Post by sayhey24 on Jun 16, 2020 11:34:36 GMT -5
Shawn - Looking at TIR from a marketing perspective during sleep time for closed loop systems makes sense as they should do really well when PWDs are not eating. The problem is the damn PWDs eat and when that happens, no matter how good the algorithms are varying unpredictable absorption weighs in. This is the problem Al was trying to address when he invented afrezza.
Closed loop systems at meal time will never, ever be as good as afrezza. This is why the best closed loop results are when they use afrezza for the meals.
At the 60-120 minute mark is about when the second dosing would occur for afrezza. Assuming diner before 7pm by the 10-11pm time range will reflect that period the PWD can act on their prandial BG.
With that said few in the RAA/Close Loop business will want a TIR period which is not 24hrs.
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Post by shawnonafrezza on Jun 16, 2020 11:48:37 GMT -5
Shawn - Looking at TIR from a marketing perspective during sleep time for closed loop systems makes sense as they should do really well when PWDs are not eating. The problem is the damn PWDs eat and when that happens, no matter how good the algorithms are varying unpredictable absorption weighs in. This is the problem Al was trying to address when he invented afrezza. Closed loop systems at meal time will never, ever be as good as afrezza. This is why the best closed loop results are when they use afrezza for the meals. At the 60-120 minute mark is about when the second dosing would occur for afrezza. Assuming diner before 7pm by the 10-11pm time range will reflect that period the PWD can act on their prandial BG. With that said few in the RAA/Close Loop business will want a TIR period which is not 24hrs. I mean, that just isn't true. They are getting quite close. They will never beat something like a non diet coke I guess. imgur.com/a/lnhH8gWThat's a commercial system. DIY as I've said are better and I only know of 2 people doing loops + Afrezza. That said I'm not arguing for or against closed loops. I'm pointing out that meals aren't gone in 90 minutes and if we assume that a basal keeps blood sugars flat, which it should, then overnight is fair game.
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Post by bababooey on Jun 16, 2020 11:56:04 GMT -5
So Mannkind failed to meet its primary end point of improved time in range. I remember many on here saying this should be the the new standard of care and A1c is obsolete. But now all of a sudden mnkd fails to show improved TIR and pumpers like sayhey try to downplay TIR. It hilarious how biased many are on here and the mental gymnastics they will go through to try and sway everything with a positive spin on it (no matter how bad). Like how some on here like to put a positive spin on dilution. I would love to see how pumpers would put a positive spin on bankruptcy as “good news”?
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Post by slugworth008 on Jun 16, 2020 12:04:40 GMT -5
So you're saying that inhaling twice is going to put people off? Yes. Both Shawn and I have said this in the past. I am totally not buying that. But that's just me.
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Post by sayhey24 on Jun 16, 2020 12:18:17 GMT -5
So Mannkind failed to meet its primary end point of improved time in range. I remember many on here saying this should be the the new standard of care and A1c is obsolete. But now all of a sudden mnkd fails to show improved TIR and pumpers like sayhey try to downplay TIR. It hilarious how biased many are on here and the mental gymnastics they will go through to try and sway everything with a positive spin on it (no matter how bad). Like how some on here like to put a positive spin on dilution. I would love to see how pumpers would put a positive spin on bankruptcy as “good news”? Baba - quite the opposite. If you read the press release it was exact as I predicted to Aged. They spun the "significant" decrease in A1c and down played the TIR. This study was a huge backhanded win for afrezza. The issue is the community does not currently appreciate the importance of TIR. Heck they don't even know what TIR means when evaluating a prandial insulin. If they did 2am in morning would not be in a prandial study. The community as a whole is still focused on A1c. Thats just a fact. So, while as Aged says it was a failed study since it did not met its primary goal, it was a huge success because it reduced A1c. If it takes A1c to finally get changes to the SoC, so be it. It took hypertension to get them to see the value of viagra.
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