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Post by prcgorman2 on Oct 4, 2024 7:44:33 GMT -5
NP - MNKD has been a company with a cult following very much like Apple in their early days when Bill Gates lent them money to kept them in business. Apple had Bill Gates and MNKD has Martine. Many of our cult followers are T1s as they know much more about diabetes and insulin. They then became the low hanging fruit for afrezza. The T2s not so much. They go to their doctor and get a pill which fails and then they get another and now a GLP1 which over time fails too. Most don't even test their BG yet most over time progress and incur heart disease and then die from a heart attack. The T2s are nearly 100% relying on their doctors who don't know. All they know is follow the SoC our great "treat to fail" protocol. There was a pretty big and new study I saw the other week about heart disease and cholesterol and BG. They were stunned that heart disease was less about cholesterol and more about BG control. That doctor told Al that many years ago that it was about BG control which started him down this diabetes path. This isn't considered definitive but I certainly wouldn't class this as GLP-1s being a treat to fail protocol. "Low quality of evidence revealed that GLP-1RAs significantly increased the incidence of prediabetes reversion to the normoglycemic state [RR = 1.76, 95% CI (1.45, 2.13), P < 0.00001] and moderate quality of evidence showed that GLP-1RAs significantly prevented new-onset diabetes [RR = 0.28, 95% CI (0.19, 0.43)" I don't think early use of insulin (inhaled or otherwise) could make any stronger claims regarding halting or reversing. The difference being that one treatment is hard on the body while the other is what the body is missing and must have. I assume reversion isn’t necessarily a permanent cure but instead a snapshot (or short video) of A1C performance. Lifestyle changes are probably required or at least very beneficial to maintaining healthy pancreatic function post reversion regardless of GLP or insulin treatment. |
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Post by ktim on Oct 4, 2024 8:46:48 GMT -5
This isn't considered definitive but I certainly wouldn't class this as GLP-1s being a treat to fail protocol. "Low quality of evidence revealed that GLP-1RAs significantly increased the incidence of prediabetes reversion to the normoglycemic state [RR = 1.76, 95% CI (1.45, 2.13), P < 0.00001] and moderate quality of evidence showed that GLP-1RAs significantly prevented new-onset diabetes [RR = 0.28, 95% CI (0.19, 0.43)" I don't think early use of insulin (inhaled or otherwise) could make any stronger claims regarding halting or reversing. The difference being that one treatment is hard on the body while the other is what the body is missing and must have. I assume reversion isn’t necessarily a permanent cure but instead a snapshot (or short video) of A1C performance. Lifestyle changes are probably required or at least very beneficial to maintaining healthy pancreatic function post reversion regardless of GLP or insulin treatment. I certainly I'm not a fan of medication. Goodness knows what possible complications might appear long term for GLP-1s. However, GLP-1 right now appear to have lots of benefits including facilitating those beneficial lifestyle changes. Insulin, whether Afrezza or otherwise, doesn't lead to people eating/drinking less and losing significant weight. You or I could hypothesize all day long about this GLP-1 craze being bad. Personally I'm 110% behind the idea that diet and exercise is the correct treatment for a prediabetic... but in the real world that simply hasn't worked. For a someone with prediabetes, the early use of insulin is the treatment that might slow down the progression... but long run probably only effective IF someone modifies the underlying lifestyle in ways most aren't likely to do. In the real world, without the modifications that is likely a treatment with progression and escalation of dependence on insulin. GLP-1s effectively come bundled with half of the lifestyle modification... the diet. Haven't heard they make you want to exercise more. And it really doesn't matter who wins the debate here on MNKD proboards because the ADA and the PBMs aren't coming here to decide how patients are going to be treated. I caveat anything I say regarding medicine, that I don't claim to know more than real medical doctors do. |
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Post by prcgorman2 on Oct 4, 2024 9:42:51 GMT -5
The difference being that one treatment is hard on the body while the other is what the body is missing and must have. I assume reversion isn’t necessarily a permanent cure but instead a snapshot (or short video) of A1C performance. Lifestyle changes are probably required or at least very beneficial to maintaining healthy pancreatic function post reversion regardless of GLP or insulin treatment. I certainly I'm not a fan of medication. Goodness knows what possible complications might appear long term for GLP-1s. However, GLP-1 right now appear to have lots of benefits including facilitating those beneficial lifestyle changes. Insulin, whether Afrezza or otherwise, doesn't lead to people eating/drinking less and losing significant weight. You or I could hypothesize all day long about this GLP-1 craze being bad. Personally I'm 110% behind the idea that diet and exercise is the correct treatment for a prediabetic... but in the real world that simply hasn't worked. For a someone with prediabetes, the early use of insulin is the treatment that might slow down the progression... but long run probably only effective IF someone modifies the underlying lifestyle in ways most aren't likely to do. In the real world, without the modifications that is likely a treatment with progression and escalation of dependence on insulin. GLP-1s effectively come bundled with half of the lifestyle modification... the diet. Haven't heard they make you want to exercise more. And it really doesn't matter who wins the debate here on MNKD proboards because the ADA and the PBMs aren't coming here to decide how patients are going to be treated. I caveat anything I say regarding medicine, that I don't claim to know more than real medical doctors do. I've been expecting plaintiff-seeking attorneys to jump on GLP-1s ASAP. I agree the weight loss part of GLP-1 treatment is good as far as it goes, but its the part where it destroys muscle tissue and stresses other organs to make up for the pancreas and insulin issues that I think is likely to be the ultimate source of class action lawsuits. I also agree that a convenient MDI (Multiple Daily Inhalation  ) of inhalable insulin isn't very likely to encourage diet and exercise lifestyle issues. IMHO, treating an insulin deficiency with insulin is better than hammering internal organs and muscle tissue. |
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Post by sayhey24 on Oct 4, 2024 10:07:12 GMT -5
NP - MNKD has been a company with a cult following very much like Apple in their early days when Bill Gates lent them money to kept them in business. Apple had Bill Gates and MNKD has Martine. Many of our cult followers are T1s as they know much more about diabetes and insulin. They then became the low hanging fruit for afrezza. The T2s not so much. They go to their doctor and get a pill which fails and then they get another and now a GLP1 which over time fails too. Most don't even test their BG yet most over time progress and incur heart disease and then die from a heart attack. The T2s are nearly 100% relying on their doctors who don't know. All they know is follow the SoC our great "treat to fail" protocol. There was a pretty big and new study I saw the other week about heart disease and cholesterol and BG. They were stunned that heart disease was less about cholesterol and more about BG control. That doctor told Al that many years ago that it was about BG control which started him down this diabetes path. This isn't considered definitive but I certainly wouldn't class this as GLP-1s being a treat to fail protocol. "Low quality of evidence revealed that GLP-1RAs significantly increased the incidence of prediabetes reversion to the normoglycemic state [RR = 1.76, 95% CI (1.45, 2.13), P < 0.00001] and moderate quality of evidence showed that GLP-1RAs significantly prevented new-onset diabetes [RR = 0.28, 95% CI (0.19, 0.43)" I don't think early use of insulin (inhaled or otherwise) could make any stronger claims regarding halting or reversing. As a starting point GLP1s do not replace insulin. The body needs insulin and it should have the correct amount for the body's needs. If you eat less with GLP1s then your body needs less insulin. If Ralph DeFronzo is correct he talks about the beneficial effects of the GLP1 on the beta cells and I would think a good part of it is the beta cells are not working as hard and have some opportunity to recover. However taking insulin does a better job and there are many studies showing early insulin intervention. However there is a huge antiglycemic market and insulin destroys that for Big Pharma and the ADA funding and research funding. If there was an insulin which mimicked the pancreas at meal time and the T2 would have a really hard time getting a severe low and you didn't need a needle to inject that would destroy this $100B market and thats what Al Mann invented with afrezza. What they are seeing and as Mike has commented numerous times is they are seeing A1cs rise again after about 2 years use of GLP1s. This is why our marketing study is evaluating an afrezza/GLP1 study. Again GLP1s are part of the treat to fail protocol no matter what claims they are trying to make - over time most T2s will continue to progress and of course incur all the other GLP1 side effects. What I can tell you which is really hard to argue with is GLP1s do not address post prandial control as can be seen with CGMs. Afrezza clearly does a significantly better job here and provides the insulin the body needs. I always smile when people tell me T2 diabetes is about insulin resistance yet we can show that if they take the afrezza before they spike and before the pancreas keeps pumping out its insulin these people need significantly less than if they wait and spike and then you try and bring down the spike. So yes, I would argue as does Bill from VDex, afrezza first, afrezza always. GLP1s are no replacement for afrezza for BG control. When it comes to weight-loss that is another subject all together. Afrezza as an adder to GLP1s could be shown to be like peanut butter and jelly. We will have to see what our marketing study says. Maybe we will hear next month some news on the Q3 call. BTW if Ralph wants to stop the heart and kidney issues he talks about he should be giving his T2 PWDs afrezza just like Al Mann told him. pulse.cardiovisual.com/video/?id=507 |
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Post by peppy on Oct 4, 2024 10:17:25 GMT -5
The reason GLP-1 are in the demand they are in, is the weight loss.
*they are generic."
Another commercial has shown up for GLP-1 on cable television. this one for 99 dollars a month.
I asked a person on GLP-1 on it for weight loss, insurance through employer. I asked if they ever tested their blood glucose level. They replied no.
One other thing, you know I like charts, LLY even with the buy backs seems to have topped and has a measured move to $700. I was wondering if that is secondary to generics hitting the market.
My understanding is, once off the GLP-1 the weight comes back.
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Post by agedhippie on Oct 4, 2024 10:47:54 GMT -5
As a starting point GLP1s do not replace insulin. The body needs insulin and it should have the correct amount for the body's needs. If you eat less with GLP1s then your body needs less insulin. If Ralph DeFronzo is correct he talks about the beneficial effects of the GLP1 on the beta cells and I would think a good part of it is the beta cells are not working as hard and have some opportunity to recover. However taking insulin does a better job and there are many studies showing early insulin intervention. However there is a huge antiglycemic market and insulin destroys that for Big Pharma and the ADA funding and research funding.... GLP-1 does not replace insulin directly, but then it doesn't necessarily need to. In T2 caused by insulin resistance the problem isn't a lack of insulin, typically you are making more than a non-diabetic, it's that it cannot be used as effectively as it should. You have two options - increase the efficiency by reducing insulin resistance, or by the brute force approach of simply taking more insulin. GLP-1 works at two levels, it increases insulin sensitivity and it reduces weight and hence insulin resistance. This lets the person live within their insulin budget and put their diabetes into remission. However, T2 is progressive so sooner or later that remission will end. Exactly when the remission ends is different in every individual, in some cases they remain in remission forever, in others it's a year or two. The conspiracy theory is just that. If insulin could put you into remission (and there is some evidence that basal insulin can do that for a limited period) then it would have been used decades ago. Insulin has been out there far longer than most antiglycemic drugs (probably sulfonylureas and metformin outside the US, would be the exceptions) and yet insulin has never been used in that role. You can always use the Newcastle Protocol and avoid needing drugs or insulin. |
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Post by agedhippie on Oct 4, 2024 10:51:42 GMT -5
The reason GLP-1 are in the demand they are in, is the weight loss. *they are generic." Another commercial has shown up for GLP-1 on cable television. this one for 99 dollars a month. I asked a person on GLP-1 on it for weight loss, insurance through employer. I asked if they ever tested their blood glucose level. They replied no. One other thing, you know I like charts, LLY even with the buy backs seems to have topped and has a measured move to $700. I was wondering if that is secondary to generics hitting the market. My understanding is, once off the GLP-1 the weight comes back. The FDA just announced that Mounjaro is no longer a shortage drug. All the compounding pharmacies to a share price hit  You don't regain all the weight, and there is a plateau around the two year mark. The protocol used in the NHS is treat to the plateau, wait a year, and then repeat if necessary. A lot of the weight regain depends on why people over-ate to begin with. If it was for psychological reasons , and a lot are, then it's going to return unless you treat the cause. |
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Post by uvula on Oct 4, 2024 11:53:18 GMT -5
Aged said: "If insulin could put you into remission (and there is some evidence that basal insulin can do that for a limited period) then it would have been used decades ago."
I have never disagreed with the Aged one until now.
Until Afrezza came along, insulin had an unacceptable hypo risk for people that didn't absolutely need to take insulin.
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Post by peppy on Oct 4, 2024 12:07:02 GMT -5
Type 2's gain weight on subq insulin.
I don't think type two's want to be on Rapid Acting Mealtime subq insulin.
They don't want to.
They don't see the pay off?
(*type two's do not gain as much weight using afrezza? Probably secondary to the first phase.)
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Post by sayhey24 on Oct 4, 2024 13:56:27 GMT -5
As a starting point GLP1s do not replace insulin. The body needs insulin and it should have the correct amount for the body's needs. If you eat less with GLP1s then your body needs less insulin. If Ralph DeFronzo is correct he talks about the beneficial effects of the GLP1 on the beta cells and I would think a good part of it is the beta cells are not working as hard and have some opportunity to recover. However taking insulin does a better job and there are many studies showing early insulin intervention. However there is a huge antiglycemic market and insulin destroys that for Big Pharma and the ADA funding and research funding.... GLP-1 does not replace insulin directly, but then it doesn't necessarily need to. In T2 caused by insulin resistance the problem isn't a lack of insulin, typically you are making more than a non-diabetic, it's that it cannot be used as effectively as it should. You have two options - increase the efficiency by reducing insulin resistance, or by the brute force approach of simply taking more insulin. GLP-1 works at two levels, it increases insulin sensitivity and it reduces weight and hence insulin resistance. This lets the person live within their insulin budget and put their diabetes into remission. However, T2 is progressive so sooner or later that remission will end. Exactly when the remission ends is different in every individual, in some cases they remain in remission forever, in others it's a year or two. The conspiracy theory is just that. If insulin could put you into remission (and there is some evidence that basal insulin can do that for a limited period) then it would have been used decades ago. Insulin has been out there far longer than most antiglycemic drugs (probably sulfonylureas and metformin outside the US, would be the exceptions) and yet insulin has never been used in that role. You can always use the Newcastle Protocol and avoid needing drugs or insulin. Would you like to address the reason why if a PWD takes afrezza prior to spiking and they stop the spike which let say would spike to 200 they may need 25% of the afrezza than what they need after they spike? Now, you are saying the body is making more insulin than it needs, yet if afrezza stops the spike we need a lot less afrezza and a lot less of all the insulin the body is releasing. Why is that? Why does the body become more resistant to insulin after the body has been releasing its insulin? You would think since the body has already released all that insulin, it has a jump start on afrezza and you would need less afrezza? Nope, you need more and usually a lot more. I will be fair to you - I ask this same question to all the experts all the time and I usually get a hand waving non-answer. I think Al Mann asked the same question of Ralph DeFronzo. I do know Al and Ralph got into at least one very heated "discussion". Then again I can be rather annoying sometimes and I get fixated on things. Jack Bogle always argued that over time the S&P 500 will out-perform nearly all other investments. Jack use to argue with himself over the 60/40, 50/50 equity/bond allocation because he knew long term - lets say the last 100 years or 10 or 20, a 100% S&P investment will outperform the 60/40 or even 80/20 model. I often see some of these Vanguard types and I always ask them the same question - if the S&P 500 will outperform all the other funds you have why do you have 300 funds? I get hand waving answers from them too. The insulin resistance question and the 300 fund question are sticky wickets which our medical "experts" and our financial "experts" don't like to hear asked. To put to rest your conspiracy theory, its not a conspiracy theory, its about the money. You know what they say - money talks and BS walks. They also say - follow the money. Big Pharma found a "miracle pill" after WWII and created a market, a huge market. They started convincing family doctors to prescribe the miracle pills of things like orinase. Give them orinase and the doctors did not need to show people how to give injections and boil needles and worry about low blood sugar. Heck, they didn't need to write scripts for the needles. Prior to afrezza, insulin was dangerous and required the needle. Al Mann fixed that but BP was already making a ton of money and the SGLT2s and GLP1s where just starting to make the market bigger and bigger. I thought by now with the CGM more T2s would be using them and more would be using afrezza. I even hoped at least a few doctors would start prescribing afrezza day 1 for the early T2s. The reality is at $1200 thats never going to happen. BTW - BP did something similar with oxycotin. They created the "pain" market and pushed the pills and made a ton a money. With them the effects were much more visible than with the antiglycimcs and high blood sugar. Of course over time it blew up. With diabetes its a quite disaster which often ends with a life ending heart attack. |
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Post by mpg54 on Oct 4, 2024 14:33:16 GMT -5
I get a little confused when I hear of the concept of Beta Cells resting. I get that they’re overloaded when a person over eats, and eventually worked to failure, but I think of it like Testosterone. Your balls shrink when you take steroids (not that I would know, never done it, going on what I’ve heard) because they are resting, as you’re replacing what they would normally produce. After repeated abuse many can’t produce Testosterone on their own any more and for some Testosterone replacement becomes for life. Wouldn’t that be the same with insulin and Beta Cells?
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Post by prcgorman2 on Oct 4, 2024 15:32:24 GMT -5
I get a little confused when I hear of the concept of Beta Cells resting. I get that they’re overloaded when a person over eats, and eventually worked to failure, but I think of it like Testosterone. Your balls shrink when you take steroids (not that I would know, never done it, going on what I’ve heard) because they are resting, as you’re replacing what they would normally produce. After repeated abuse many can’t produce Testosterone on their own any more and for some Testosterone replacement becomes for life. Wouldn’t that be the same with insulin and Beta Cells? You just answered for me why testosterone is sold as "supplements". |
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Post by mpg54 on Oct 4, 2024 18:04:56 GMT -5
I get a little confused when I hear of the concept of Beta Cells resting. I get that they’re overloaded when a person over eats, and eventually worked to failure, but I think of it like Testosterone. Your balls shrink when you take steroids (not that I would know, never done it, going on what I’ve heard) because they are resting, as you’re replacing what they would normally produce. After repeated abuse many can’t produce Testosterone on their own any more and for some Testosterone replacement becomes for life. Wouldn’t that be the same with insulin and Beta Cells? You just answered for me why testosterone is sold as "supplements". It is? Never heard of Testosterone being an “over the counter” supplement. Nevertheless, if you’re not using your Beta Cells/Balls ya lose their ability to produce, right? Of course, I get it that it’s long term usage that would lead to this, but is resting necessarily better? I’m sure there would need to be studies to prove that out. |
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Post by agedhippie on Oct 4, 2024 19:34:55 GMT -5
Would you like to address the reason why if a PWD takes afrezza prior to spiking and they stop the spike which let say would spike to 200 they may need 25% of the afrezza than what they need after they spike? Now, you are saying the body is making more insulin than it needs, yet if afrezza stops the spike we need a lot less afrezza and a lot less of all the insulin the body is releasing. Why is that? Why does the body become more resistant to insulin after the body has been releasing its insulin? You would think since the body has already released all that insulin, it has a jump start on afrezza and you would need less afrezza? Nope, you need more and usually a lot more. ... This is the last time I am answering this question for you since it has been answered several times already so you don't appear to be retaining the information. As your blood sugar rises you become more insulin resistant. This occurs in T1 and T2 giving a lower I:C ratio so you need more insulin. If you stop the spike then your I:C ratio isn't changing so you don't need that 25% more insulin. The body definitely gets the jump on Afrezza,with it's own insulin, but the body cannot produce enough insulin to overcome the insulin resistance and so you have a relative deficiency. Adding insulin, any insulin, fills that gap. however, it makes matters worse as you down regulate the insulin receptors even harder, but you can always add more insulin - there is no upper limit. Insulin is a brute force approach which is why it's not popular with doctors who would rather address the issue with drugs that improve insulin sensitivity where they can. This is all 101 stuff and any diabetes textbook will explain it for you, you just need to read. Some endos prescribe GLP-1 for T1, not for weight loss but rather to increase insulin sensitivity. That's off-label though. |
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Post by agedhippie on Oct 4, 2024 19:40:04 GMT -5
I get a little confused when I hear of the concept of Beta Cells resting. I get that they’re overloaded when a person over eats, and eventually worked to failure, but I think of it like Testosterone. Your balls shrink when you take steroids (not that I would know, never done it, going on what I’ve heard) because they are resting, as you’re replacing what they would normally produce. After repeated abuse many can’t produce Testosterone on their own any more and for some Testosterone replacement becomes for life. Wouldn’t that be the same with insulin and Beta Cells? Actually it's sort of true. If you gain weight your insulin requirement rises and your body builds more beta cells in response. This is why the majority of even morbidly obese people are not diabetics. If you lose weight you body will not replace those beta cells as they die (apoptosis, all cells have a lifetime and where this fails you can get cancers). If you are taking extra insulin it is to fill a deficiency, either absolute (T1), or relative (T2) so there is no change to the beta cells. |
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) of inhalable insulin isn't very likely to encourage diet and exercise lifestyle issues. IMHO, treating an insulin deficiency with insulin is better than hammering internal organs and muscle tissue.
