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Post by agedhippie on Mar 21, 2023 14:49:39 GMT -5
... The result will be that Afrezza is superior since the competitor is a placebo and insulin will always win (basal alone would be superior against a placebo!) What do you think the placebo is? It will be pure TS.
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Post by agedhippie on Mar 21, 2023 14:19:27 GMT -5
I'm hoping the "wildcard" is the India trial data. The average applicant was BG over 10. The corrected dosing HAS to make a difference for these folks. If it's as good as Al thought it could be, truly superior, then it sets the stage with tremendous buzz being created around our forgotten product leading up to our all-important Pediatric trial readout. A superior result in India also HAS to bring T2's right back into our sights. This is the India trial - ctri.nic.in/Clinicaltrials/showallp.php?mid1=45751&EncHid=&userName=CiplaIt has the same protocol as Affinity-2, the Phase 3 T2 trial, so the results shouldn't be that different. It's 216 people split into two arms on oral meds with an HbA1c between 7.5 and 10. The treatment is "Inhalation of Appropriate dose of Technosphere® Insulin, just before 3 major meals (breakfast, lunch, and dinner) for 24 Weeks." The primary outcome is the HbA1c difference between Afrezza and the placebo, the secondary outcomes are: - the change in fasting plasma glucose (FPG) from between TI and placebo groups 12 Weeks and 24 Weeks - the change in HbA1c from between TI and placebo groups 24 Weeks - the proportion of subjects achieving HbA1c ≤7% between TI and placebo groups; 12 Weeks and 24 Weeks - the proportion of subjects requiring rescue treatment for hyperglycaemia between TI and placebo groups. The result will be that Afrezza is superior since the competitor is a placebo and insulin will always win (basal alone would be superior against a placebo!)
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Post by agedhippie on Mar 20, 2023 22:52:30 GMT -5
Well, Nick is heavily onto CGM. Now that we have some tests under our belt that we can go back to Nick with, my hope is that he would be interested now more than he was at that time. At minute 4:15 or so in that interview, Nick was saying how during concerts his team can see when a low sugar period will start to hit and prepare him for it in advance. With Afrezza he would probably not need anywhere near that much preparation. He is getting caught up on the basal insulin. The problem is that exercise, fast twitch muscle fibres specifically, pulls glucose directly from the blood bypassing the need for insulin entirely. He uses an Omnipod so he will be running a temporary basal profile (less than normal) to allow for exercise, but if he works to hard his levels will drop. As it is someone can plant a soda somewhere he can pick it up when they see him dropping.
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Post by agedhippie on Mar 19, 2023 13:09:49 GMT -5
What I can show is if we "Stop the Spike" with afrezza we need 2x 3x less. You are also convinced that high blood sugar is causing insulin resistant. So, if we stop the high blood sugar by stopping the spike I would think we should be able to solve the insulin resistance issue. In other words "You" have solved the problem and afrezza should provide a path towards stopping the progression and reversing the disease. Agreed? I actually curious about the 2x to 3x less insulin claim. Is there supporting trail data for that? And does that include getting back to baseline? I am not sure I have seen that paper. You are confusing acute and chronic insulin resistance. Chronic insulin resistance is what means you at say 200 need a carb ration of maybe 1u per 3g of carbs vs. 1u per 20g of carbs, its the underlying condition. The acute case is what I was talking about where the ratio itself fluctuates and that is caused by down regulation (read the paper) so that 1:20 ration becomes a 1:15 ratio at 350, but as soon as you drop back to 200 you will revert to 1:20 because the down regulation is no longer occurring. I can see a path to using less insulin in the acute case since you are not reaching as far into down regulation so you remain more insulin sensitive and need less insulin, however the baseline (chronic) insulin resistance is untouched. There is no evidence I know of currently that Afrezza addresses the chronic case (which is the one doctors care about), just theories and assertions, so write the paper that proves it.
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Post by agedhippie on Mar 19, 2023 9:45:17 GMT -5
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Post by agedhippie on Mar 19, 2023 9:40:33 GMT -5
He is desperate for good publicity, less so about helping diabetics. He is proposing $30 for a vial of insulin (10mL) while Lilly have already said they are going to sell that for $25 from May.
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Post by agedhippie on Mar 19, 2023 9:33:22 GMT -5
Wow - now you are trying to blame rising blood glucose as the cause for resistance. Lol. Focus! Your question was why does it take more insulin to bring down a high spike. The answer is the down regulation of receptors. You are assuming that it takes the same number of units to reduce your level from, say, 300 to 200 as it does from 200 to 100. That's untrue. It takes more insulin to go from 300 to 200 despite that fact that in both cases there is a drop of 100. Welcome to my world, this is just one of those interesting quirks that make management so much harder than people think. You don't seem to have got past the introduction, not that it matters because the medical world has. If this is about you wanting to feel that you have solved diabetes if only the world would listen then mission accomplished. If you actually want to solve diabetes then you need to produce a paper that survives peer review and start socializing it in the medical community
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Post by agedhippie on Mar 19, 2023 9:22:44 GMT -5
The user claims (and I believe it) that there is a delay between blood stream glucose levels and interstitial blood glucose levels. Is there even more of a delay with apple watch skin surface glucose levels? If so maybe the apple watch will never be good enough for real medical use. I find the lag is between 15 to 20 minutes. It's why if your levels are changing fast you use a finger stick, which only lags by 5 minutes, rather than a CGM. Exercise is one of those things that induces big swings. CGMs attempt to reduce the apparent lag with predictive algorithms, but generally this video from Abbott explains the issue: www.youtube.com/watch?v=I3tQ80NXvGk
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Post by agedhippie on Mar 18, 2023 18:41:03 GMT -5
I think we are saying the same thing - they did just pick up all the Medicare patients on basal. However, you are saying they are going to stop there? Man thats Step 4 and a limited group. They are going to start pushing for all the T2s to be on insulin. Robert Ford already publicly said that. ... Lets look at the numbers. Generally around 29M people in the US have diabetes, and about 90% of those are Type 2 so that's about 26M and 14% of those are on insulin and currently about 3% are on CGMs. That means that today there is an immediate open market of just over 3.6 million peoples (or 1.5x the Type 1 market). But wait, that's the entire diabetic market, not just the Type 2 Medicare market. Good catch. The SoC already says that basal users should be on a CGM; Real-time continuous glucose monitoring or intermittently scanned continuous glucose monitoring can be used for diabetes management in adults with diabetes on basal insulinAll Medicare did was agree. That's a big deal because insurance companies drag their feet over the SoC, but jump once Medicare acts - that was true with CGMs for Type 1s, and also true for pumps. So where does that leave Robert Ford? He is targeting a 15% CAGR and that can easily be done within those numbers. This is low hanging fruit, the endos already believe in CGMs so getting endos to write prescriptions for existing insulin users is all he needs to do. The insulin market has been static for years, the GLP-1 market is growing hugely (look at Mike's slides from that last presentation), that is why their next target will be non-insulin users - you don't fight the trend.
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Post by agedhippie on Mar 18, 2023 13:38:05 GMT -5
... I believe the new CGM payment rule starts in April 2023 so we will start seeing how many T2s are now getting Tresiba before the SGLT2/GLP1 so they can get the CGM. In other words - breaking the SoC guidelines. What's the TIR for Tresiba vs the GLP1? I know you posted it not long ago. I am sure the Abbott reps have a zillion studies showing why the doctors should prescribe insulin today and not wait as the SoC says. I doubt the reps are going to be that concerned for a while as they just picked up all the Medicare patients on basal insulin. It's going to take a while to absorb that group. TIR was 91% for GLP-1 and 75% for basal (+/- a couple of percent, I can't be bothered to look it up again.) Dexcom and Abbott have moved past insulin users (they have those groups now) and are after the GLP-1 and SGLT2 user market.
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Post by agedhippie on Mar 17, 2023 17:02:35 GMT -5
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Post by agedhippie on Mar 17, 2023 16:46:17 GMT -5
However, he should be thanking you for pointing out afrezza was not on the 2023 formularity. This allowed both his team and mine to work with CMS in December and for CMS to determine that not only would they follow the pre auth process but afrezza would be a near blanket approval. At the time they said 80% but I think the current number is 90%+. ... The Plan D providers do make baskets based on negotiation with the CMS after they respond to the bid package which included that spreadsheet of drugs they are required to provide prices on. Various box configurations of afrezza were included in the spreadsheet. His team and mine? Is there something we should know? Mike didn't mention pre-auth on the call that has just gone despite talking about the impact of the CMS changes. I have seen no determination from CMS stating that pre-approval will be prohibited for Afrezza, likewise I have seen nothing from CMS saying that an insurer will be compelled to offer Afrezza. Is this published or a theory? To be clear on baskets of drugs. Novo Nordisk can say if you make Tresiba and Novolog your preferred insulins then we will do a deal on Ozempic which has a nice juicy rebate. That's the basket I meant - using high value drugs to lock out competitors for the low value commodity drugs.
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Post by agedhippie on Mar 17, 2023 10:46:24 GMT -5
Well said - let me add Mike continues to mention $35 Medicare afrezza. If he removes the pre auth in 2024 it is an attractive approach for CGM vendors targeting the T2 market to meet the "insulin treated" Medicare requirement for CGM payment. In that presentation there are two things that stand out; MNKD is focused on Afrezza for Type 1 and V-Go is for Type 2, and a comment that both medicare and commercial co-pays were capped at $35. Is that second point really true because I never knew that? Mike doesn't mention removing pre-auth, probably because that's a decision the insurer makes and will be tied to the pharma's rebate packages. Pharmas create baskets of drugs so while the rebate on insulin may be negligible the rebate on the non-insulin drugs like GLP-1 could be huge - if their insulin isn't preferred then no juicy GLP-1 rebates.
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Post by agedhippie on Mar 16, 2023 23:22:17 GMT -5
... What you are saying about weight causing the resistance is not what it being seen with CGM results. The reason diet and exercise works is first the pancreas needs to release less "insulin" as the reduce body mass is "taking the load" off the pancreas and the insulin need is reduced. Exercise helps because of the same reason TZDs help - you make new cells (muscle with exercise vs fat) with brand new receptors. The reason non-diabetic obese grow additional beta cells is because of the increased body mass and the body's need for additional insulin. The diabetic obese don't grow the additional beta cell mass. ... Aged - I will ask you the same question regarding insulin resistance since you think Gerry Shulman won't answer. Why is it if you stop the spike the T2 needs 2x maybe 3x less than if they spike and then try and bring down the spike with the same carb load? Why does the insulin resistance change so rapidly? Its clearly not a theory as we can demonstrate it. I might not have phrased that clearly enough in my post. Restating; the loss of weight reduces the insulin resistance which means your beta cells can now produce enough insulin to maintain your levels. (There is still the issue of this not working over time since diabetes is progressive, but in the immedate and ideally medium term this is true.) Exercise reduces levels in the long term because of weight loss, and in the short term because fast-twitch muscles take up glucose directly (no insulin involved) from the blood stream. And diabetic obese people do grow additional mass, just not as much as they need. The answer is simple, as your blood glucose increases so does your insulin resistance as your receptors down regulate. Terminating the spike early avoids down regulation but does not solve insulin resistance - this is why dosing is not always a simple ratio. If you want to understand about insulin resistance properly I suggest this paper, Trends in insulin resistance: insights into mechanisms and therapeutic strategy, which explains the multiple mechanism for insulin resistance and signaling.
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Post by agedhippie on Mar 16, 2023 18:22:20 GMT -5
Stevil - The SARS-CoV-2 virus is just one of the viruses attacking the beta cells. I don't think that is up for debate. We see it in autopsies and lab experiments. We also know there are a lot more people getting T2 after having Covid. That is also a fact. Joslin isolated 4 other distinct viruses years ago and were working on more. God only knows what the total virus population could be. One theory is we have T2 hotspots because the virus has spread in a community like Pottsville PA. Is that theory correct IDK but Pottsville is not like the Puma indians which we can dismiss to being a gene thing. What happens if different viruses attack the beta cells? I bet you would have variants of diabetes. We also know from autopsy that fat non-diabetics grow more beta cells. The body adapts. Thats a fact based on autopsy. Blaming diabetes on gaining too much weight does not work with a healthy body. It is only after the beta cells have been compromised and can no longer grow enough mass to make "good" insulin. It is also not what the tech diet companies are seeing. They are seeing loss of post prandial control prior to the weight gain. Based on what you are saying it should be the other way around. I did reach out the Gerry Shulman and poised the same question to him which I did to you. Why is it that insulin resistance can rapidly increase when we do not stop the post meal spike? When I hear back I will let you know what his answer is. Did you try the post meal spike experiment with afrezza? I bet if you did you see what I am saying. That theory was discredited by Mount Sinai researchers last year. They found that COVID attacks all of the pancreas, not just the beta cells, and additionally the cells did not die. The evidence that COVID caused diabetes is not now generally thought to be reliable. As to Type 2 diabetes the current view is that this a combination of people who were previously diabetic but undiagnosed (CDC reckons about 8.5 million people in the US are undiagnosed) who were uncovered either in treatment or follow-up, and people who became diabetic for a period under the stress from the disease (high cortisol levels will do that) but cleared up afterwards. It's likely that the latter group are predisposed towards diabetes (think pre-diabetic) and would have developed diabetes anyway. With weight you are conflating issues. Weight causes insulin resistance which the body reacts to by building extra beta cells. Certain genes compromise the build out of those beta cells and hence you get diabetes. This is why diet and exercise helps with diabetes because it reduces your insulin resistance to a point where your insulin is sufficient again (the Newcastle Diet). Lacking the relevant genes you can grow to the size of a small killer whale with no sign of diabetes. It's interesting that you pick Joslin because they have done a lot of works into genetics and epigenetics relating to Type 2. I expect his admin either deletes it before it even gets to him, or sends a rote response (after all you may want to donate money). Either way until there is trial data showing a link nobody will be interested because it's just another random theory, although they may fake it for a decent sized donation
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