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Post by prcgorman2 on Sept 29, 2022 16:29:32 GMT -5
Hyperinsulinemia and insulin resistance are conditions caused by a diet that elevates blood sugar all day long or is highly inflammatory. Try testing someone that is about to be diagnosed with metabolic syndrome or pre diabetes , that is NOT on any treatment yet... and you will see these markers are most likely are out of control in those patients. These conditions have nothing to do with treating high blood sugar with insulin. The treatment using insulin comes after the T2D diagnosis, and yes, introducing more insulin into the treatment of someone that continues to sabotage their own body with food and drink, that caused the problem in the first place, is an uphill battle. Educate the patients about the root cause of Hyperinsulinemia, metabolic syndrome , insulin resistance and type 2 diabetes. Reversing these conditions is as simple as eliminating the root cause. The data from randomized clinical trials in humans is out there. www.bmj.com/content/bmj/372/bmj.m4743.full.pdfNow you're confusing me. Is the proper treatment then a low carb diet or Afrezza? I'm not taking offense to everyone who is trying to educate me but I do find it to be amusing. Do you all not realize I have spent the last 8 years of my life studying this stuff? While I didn't get my PhD honing in on specifics, my medical degree is no slouch, either. By all means please keep sharing information as I never want to get too smart to learn but the hubris of this board is sometimes appalling. It gets frustrating trying to share medical consensus when you're met at every turn with resistance and people who suffer from the Dunning-Kruger effect because they've read books or online articles. Look, Afrezza is amazing. It is truly a medical breakthrough when it comes to insulin. It's the closest humans will ever get to a physiologic insulin. The problem with diabetes is that it's not just a disease of insulin. I'm not saying that I have all the answers. I'm saying quite the opposite. I don't have the answers, which is why studies and trials are so important. The scientific method uses observation over time to complete. Thus far, Afrezza is in a courtroom with both prosecution and defense holding a substantial case. There does not yet exist enough evidence, either way to form a verdict and it's going to be stuck in court for many years until one can be reached. That's all I'm saying. I can see the benefits of early use of Afrezza from a theoretical perspective. But those who want to change the standard of care based off theory alone reveal their ignorance with how good science works. And to make things worse, I try to help people understand how doctors think so they can be patient with the process and understand doctors aren't (all) imbeciles and there are actually legitimate reasons why Afrezza has not been a success thus far- and why it probably won't significantly change unless the peds trial is a success. I'm happy to keep posting to help those who want to understand and learn, but you all make this exhausting sometimes. Thank you Stevil. I wish you wouldn't wait so long between posts.
Mango said something that I think should resonate with you, but wanted to ask if it does.
"Afrezza will ultimately receive the recognition it deserves and rightful place as the Gold Standard of mealtime insulin within the Standards of Care."
I've been thinking about your most recent posts, and I came back to something close to what Mango said. Basically, even if the SoC for T2s doesn't change, Afrezza should still be the dominant prandial insulin because of its ultra-rapid performance, and hell, convenience. Now, that assumes a lot of things, including lower costs to the PWDs, more in line for what they're paying for RAAs. That may not be realistic, but if we only focus on what Afrezza is, and the PK/PD profile, and access to CGMs to attempt to manage TIR better, than Afrezza is (or more correctly, should be) a winner (says the non-PWD guy without an MD title).
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Post by sportsrancho on Sept 29, 2022 16:31:06 GMT -5
I do believe the answer is to open a ton of Vdex facilities. I say that not bc of my obvious bias but bc the MNKD marketing team has tried for 6+ years to get sales to ramp and it hasn’t happened. The fault isn’t with the sales/marketing team. I think MNKD has had good people in place. They just can’t do much bc of the label constraints. I think a better approach would be to STOP trying to sell it conventionally, eliminate the sales force and put money into new studies. There’s a specific strategy on the studies that I’d favor but even if they just tackle some of the obvious areas it would help. This drug needs a relaunch ~Bill What do see as the label constraints? What would you like to see the label say which will have doctors become prescribers? The label: it needs to address actuality of significantly lower hypo risk. Why don’t docs & patients like insulin? Needles. Check, we’re good there and hypo risk. Prove lower (virtually non-existent) hypo risk and docs will use more AND USE EARLIER. This is key. Much evidence suggests EARLIER use of insulin (in Type 2s) will halt disease progression and even reverse disease. Early use of Afrezza dramatically changes course, severity and outcomes from disease. And changes course of scripts 😏 ~Bill |
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Post by mango on Sept 29, 2022 18:27:29 GMT -5
What do see as the label constraints? What would you like to see the label say which will have doctors become prescribers? The label: it needs to address actuality of significantly lower hypo risk. Why don’t docs & patients like insulin? Needles. Check, we’re good there and hypo risk. Prove lower (virtually non-existent) hypo risk and docs will use more AND USE EARLIER. This is key. Much evidence suggests EARLIER use of insulin (in Type 2s) will halt disease progression and even reverse disease. Early use of Afrezza dramatically changes course, severity and outcomes from disease. And changes course of scripts 😏 ~Bill We’ve all been sayin’ it on here for years, Afrezza is the safest insulin on the market. And if we really want to be honest here, safest diabetes treatment, period. If we could get what Bill is suggesting then that would be SoC changing stuff. A large scale STAT study ought to do the trick. |
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Post by stevil on Sept 29, 2022 22:17:43 GMT -5
Thank you Stevil. I wish you wouldn't wait so long between posts.
Mango said something that I think should resonate with you, but wanted to ask if it does.
"Afrezza will ultimately receive the recognition it deserves and rightful place as the Gold Standard of mealtime insulin within the Standards of Care." 100% can stand behind that comment. But I think more still needs to be done due to lack of awareness and familiarity. To piggy back off of Bill’s comment about hypos being nearly non-existent- they need to do better than TIR and actually focus on reportable events from hypoglycemia. This will be challenging because it’s unethical to try to induce hypoglycemia and there isn’t a very large sample size to begin with. But it is a more powerful statistic to me to have fewer hospitalizations/deaths with improved A1c (current measuring stick) than it is to have better TIR because at that point you’re measuring hypoglycemia in a measurement of time when it may be an insignificant consequence if it doesn’t lead to mortality. In other words, who cares if you spend 5% more time in hypoglycemia if there are no consequences from it? I’d love to see MNKD dose more aggressively to prove Bill’s assertion in a respected journal. hypoglycemia is by far the #1 fear when treating people with diabetes. Proving the safety of Afrezza would make it the standard of care for insulin and nearly entirely eliminate basal insulin except for functionally type 1 type 2s. |
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Post by sweedee79 on Sept 30, 2022 1:28:37 GMT -5
Now this is some really great discussion... So how do we get a large scale trial going that proves the safety of Afrezza so we can become the SOC?
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Post by sportsrancho on Sept 30, 2022 7:29:22 GMT -5
“One point that I failed to make but needs to be added to this discussion is that while hypos are a significant obstacle to insulin use by docs and patients, this is especially true for all PRANDIAL insulins. To the extent that docs use insulin, they’re much more comfortable with basal than prandial. Afrezza’s is a prandial so it’s the last therapeutic agent used. ADA protocol specifies this.
Now, it is well understood that BG control is first a prandial problem. That’s where one first loses control. Yet docs when finally initiating insulin start a patient on basals. It’s the wrong treatment. What really makes Afrezza spectacular is it’s ability to target the problem of prandial control. That’s why patients see such great results. This is why Afrezza should be used way earlier (and in my opinion) and almost exclusively. When used that way you see A1c improvement that CANNOT be achieved with any other pharmaceutical agent.
So, just to be totally clear, the hypo problem really impacts Afrezza bc it’s a prandial. That’s why it’s so important to get the marketplace to understand Afrezza just doesn’t have significant hypo risk.
Sorry I’m running on, but when a doc understands a little about Afrezza they’ll say things like, “yes I understand Afrezza has a lower hypo risk bc it’s not in the patient’s system very long.” That’s true but only partially correct. There’s more to it that most docs never hear: Afrezza’s hypo risk is lower largely bc it activates hepatic supply of glucose as BG levels begin to drop. That’s the real safety mechanism, NOT how long Afrezza’s in the system. Of course, this is what happens with healthy nondiabetic people.”
~Bill
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Post by prcgorman2 on Sept 30, 2022 8:06:06 GMT -5
“One point that I failed to make but needs to be added to this discussion is that while hypos are a significant obstacle to insulin use by docs and patients, this is especially true for all PRANDIAL insulins. To the extent that docs use insulin, they’re much more comfortable with basal than prandial. Afrezza’s is a prandial so it’s the last therapeutic agent used. ADA protocol specifies this. Now, it is well understood that BG control is first a prandial problem. That’s where one first loses control. Yet docs when finally initiating insulin start a patient on basals. It’s the wrong treatment. What really makes Afrezza spectacular is it’s ability to target the problem of prandial control. That’s why patients see such great results. This is why Afrezza should be used way earlier (and in my opinion) and almost exclusively. When used that way you see A1c improvement that CANNOT be achieved with any other pharmaceutical agent. So, just to be totally clear, the hypo problem really impacts Afrezza bc it’s a prandial. That’s why it’s so important to get the marketplace to understand Afrezza just doesn’t have significant hypo risk. Sorry I’m running on, but when a doc understands a little about Afrezza they’ll say things like, “yes I understand Afrezza has a lower hypo risk bc it’s not in the patient’s system very long.” That’s true but only partially correct. There’s more to it that most docs never hear: Afrezza’s hypo risk is lower largely bc it activates hepatic supply of glucose as BG levels begin to drop. That’s the real safety mechanism, NOT how long Afrezza’s in the system. Of course, this is what happens with healthy nondiabetic people.” ~Bill Tell Bill thank you. You and he (and plenty of others I’m sure) know I was not a fan of his because of HfM, but I respect that he’s put his money where his mouth is, and he and his company are making real, meaningful, contributions to benefit PWDs, and Mannkind investors. I pray he is richly rewarded for his passionate efforts. |
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Post by agedhippie on Sept 30, 2022 8:35:38 GMT -5
...who cares if you spend 5% more time in hypoglycemia if there are no consequences from it? ... This is the bit I keep banging on about. Features do not matter, just outcomes. If there is no impact from mild hypos why do I care if they are marginally reduced? The same applies for after meal spikes - they sound like they are bad, but are they and if so how bad? These things need to be quantified before changes will happen because you have to evaluate risk reward. |
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Post by sayhey24 on Sept 30, 2022 8:47:00 GMT -5
...who cares if you spend 5% more time in hypoglycemia if there are no consequences from it? ... This is the bit I keep banging on about. Features do not matter, just outcomes. If there is no impact from mild hypos why do I care if they are marginally reduced? The same applies for after meal spikes - they sound like they are bad, but are they and if so how bad? These things need to be quantified before changes will happen because you have to evaluate risk reward. Post meal spikes and elevated BG levels are bad, really bad. We see it in heart attack numbers. SGLT2s are running around saying they are heart healthy. Why? The reality is the PWD is still in an elevated BG state causing vascular damage. They are just not sitting in even high numbers. With afrezza there is no need to have the T2 sitting >140. The risk of the T2 getting a severe hypo using afrezza is very low. Maybe, with CGMs we will start seeing some of those long term studies kick off. Are near term changes going to happen - fat chance. The ADA will do everything it can to bury afrezza. |
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Post by sayhey24 on Sept 30, 2022 8:55:06 GMT -5
“One point that I failed to make but needs to be added to this discussion is that while hypos are a significant obstacle to insulin use by docs and patients, this is especially true for all PRANDIAL insulins. To the extent that docs use insulin, they’re much more comfortable with basal than prandial. Afrezza’s is a prandial so it’s the last therapeutic agent used. ADA protocol specifies this. Now, it is well understood that BG control is first a prandial problem. That’s where one first loses control. Yet docs when finally initiating insulin start a patient on basals. It’s the wrong treatment. What really makes Afrezza spectacular is it’s ability to target the problem of prandial control. That’s why patients see such great results. This is why Afrezza should be used way earlier (and in my opinion) and almost exclusively. When used that way you see A1c improvement that CANNOT be achieved with any other pharmaceutical agent. So, just to be totally clear, the hypo problem really impacts Afrezza bc it’s a prandial. That’s why it’s so important to get the marketplace to understand Afrezza just doesn’t have significant hypo risk. Sorry I’m running on, but when a doc understands a little about Afrezza they’ll say things like, “yes I understand Afrezza has a lower hypo risk bc it’s not in the patient’s system very long.” That’s true but only partially correct. There’s more to it that most docs never hear: Afrezza’s hypo risk is lower largely bc it activates hepatic supply of glucose as BG levels begin to drop. That’s the real safety mechanism, NOT how long Afrezza’s in the system. Of course, this is what happens with healthy nondiabetic people.” ~Bill I fully agree - the historical reason has been needles and hypos. Now we also have BP and their antiglycemics. They will do whatever they can to keep their SGLT2s and GLP1s at the top of the ADA's SoC and will try to keep afrezza hidden. The thing with VDex is you are not following the ADA's SoC. You are following the VDex SoC. This is clearly a better SoC based on your PWD's results. How do we get other doctors to use your SoC? Can anything be done to pick-up the pieces from the failed "Seeing is Believing" campaign? |
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Post by agedhippie on Sept 30, 2022 9:02:26 GMT -5
This is the bit I keep banging on about. Features do not matter, just outcomes. If there is no impact from mild hypos why do I care if they are marginally reduced? The same applies for after meal spikes - they sound like they are bad, but are they and if so how bad? These things need to be quantified before changes will happen because you have to evaluate risk reward. Post meal spikes and elevated BG levels are bad, really bad. We see it in heart attack numbers. SGLT2s are running around saying they are heart healthy. Why? The reality is the PWD is still in an elevated BG state causing vascular damage. They are just not sitting in even high numbers. With afrezza there is no need to have the T2 sitting >140. The risk of the T2 getting a severe hypo using afrezza is very low. Maybe, with CGMs we will start seeing some of those long term studies kick off. Are near term changes going to happen - fat chance. The ADA will do everything it can to bury afrezza. TBH I think spikes are bad as well, but I cannot quantify how bad. Both SGLT2 and GLP-1 reduce heart failure, and more interestingly they do this in non-diabetics as well. In other words it's not tied to blood glucose. Why do they say they are heart healthy (SGLT2 in particular)? Large scale trial data. The ADA will go with GLP-1 for Type 2 because it addresses multiple aspects of diabetes at once, and not just the relative insulin deficiency. |
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Post by mango on Sept 30, 2022 9:10:19 GMT -5
As the holders of the Holy Grail of Diabetes it’s our responsibility and duty to see Afrezza permeates within the medical community and becomes the Gold Standard in Mealtime Therapy. It’s time to use our newly acquired funds to launch multiple large scale, long term clinical trials which will have key elements in the Primary and Secondary Outcome Measures that will exploit and highlight Afrezza’s best attributes, which will in turn forever change the landscape of diabetes care. We need a large scale, long term STAT clinical trial with 400+ participants and run 1-1.5 years. Superiority trial. We need a Landmark Hypoglycemia clinical trial showing Afrezza is the safest insulin on the market. Large scale, long term clinical trial. Superiority trial. We need a large scale, long term clinical trial in Type 2 Diabetes highlighting early intervention with Afrezza to become the Gold Standard in T2D. We need 1000+ participants and this also needs to be 52+ weeks. Superiority trial. It’s time to call michaelcastagna into action. |
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Post by agedhippie on Sept 30, 2022 9:45:20 GMT -5
... The thing with VDex is you are not following the ADA's SoC. You are following the VDex SoC. This is clearly a better SoC based on your PWD's results. How do we get other doctors to use your SoC? Can anything be done to pick-up the pieces from the failed "Seeing is Believing" campaign? Mostly you won't get doctors to change because the ADA SoC is seen as a very well sourced consensus view (which it is). It provides a panel of experts in the field all saying this is what you should do. However, doctors are at liberty to modify or ignore the SoC if they think they have a better treatment - it just tends to be very rare. |
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Post by sayhey24 on Sept 30, 2022 9:57:42 GMT -5
Post meal spikes and elevated BG levels are bad, really bad. We see it in heart attack numbers. SGLT2s are running around saying they are heart healthy. Why? The reality is the PWD is still in an elevated BG state causing vascular damage. They are just not sitting in even high numbers. With afrezza there is no need to have the T2 sitting >140. The risk of the T2 getting a severe hypo using afrezza is very low. Maybe, with CGMs we will start seeing some of those long term studies kick off. Are near term changes going to happen - fat chance. The ADA will do everything it can to bury afrezza. TBH I think spikes are bad as well, but I cannot quantify how bad. Both SGLT2 and GLP-1 reduce heart failure, and more interestingly they do this in non-diabetics as well. In other words it's not tied to blood glucose. Why do they say they are heart healthy (SGLT2 in particular)? Large scale trial data. The ADA will go with GLP-1 for Type 2 because it addresses multiple aspects of diabetes at once, and not just the relative insulin deficiency. If the insurance study is true GLP1s serve no long term benefit as most T2s stop using within 2 years. Short term the T2 significantly reduces food consumption and absorption and the obvious thing is weight loss but then BOOM - the root cause was not addressed and the BG starts to rise. Then what does the SoC say to do - add the SGLT2? Brilliant. Two years lost. The weight loss is fine but they seem to just add it back. I agree the ADA is going with the GLP1s. The last thing they want to do is see BP lose $10B in sales. I also think Mike needs to figure out a plan to combine afrezza usage with the GLP1s. When they stop with the GLP1s they will still have the afrezza. |
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Post by peppy on Sept 30, 2022 10:02:17 GMT -5
... The thing with VDex is you are not following the ADA's SoC. You are following the VDex SoC. This is clearly a better SoC based on your PWD's results. How do we get other doctors to use your SoC? Can anything be done to pick-up the pieces from the failed "Seeing is Believing" campaign? Mostly you won't get doctors to change because the ADA SoC is seen as a very well sourced consensus view (which it is). It provides a panel of experts in the field all saying this is what you should do. However, doctors are at liberty to modify or ignore the SoC if they think they have a better treatment - it just tends to be very rare. I think I have noticed a pattern, The board talks about Afrezza prescriptions numbers, and Aged comes on line and saids, NOPE. It is never the system that is wrong. We seem to be the tiger, caught by the toe. The worlds best acting meal time insulin stopped by protocols. |
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