|
|
Post by stevil on Jan 22, 2024 2:29:06 GMT -5
*don’t get any newly diagnosed type 2s on a CGM.
|
|
|
|
Post by sayhey24 on Jan 22, 2024 7:35:33 GMT -5
*don’t get any newly diagnosed type 2s on a CGM. Step "0" of the SoC should be put get the AGP of all diabetics including the prediabetics before any medication is prescribed. This was actually not something VDex was doing in their early days, if I remember correctly. Could you imagine if this was actually done and post prandial numbers where exposed for all the antiglycemics. What a fire storm that would be. Let me ask you a question - you said - " Mounjaro fixes the underlying problem of insulin sensitivity and takes no work by the person using it" ... Most likely to succeed in reducing A1c with minimal effort and potentially no lifestyle change? Mounjaro." Why is it as Mike has mentioned numerous times that maybe Mounjaro works for 2 years and then the numbers start to rise again? While it may take "no work" aside from the belly ache, it is not the medically correct way to treat these people which was the topic of a very heated discussion between Al and Ralph. Now we know we get about 2 years or better said, another "failed" step in the SoC. |
|
|
|
Post by sayhey24 on Jan 22, 2024 7:52:53 GMT -5
^What he said. The CDSCO rejected Cipla’s application to sell Afrezza without a local trial and required a trial. The quickest and easiest way to fix that is replicated the US phase 3 trial which is what they are doing. As CIPLA did not appear in Mike's JP Morgan Slides and Mannkind/Afrezza did not seem to appear anywhere in the recent CIPLA update/projection/pipeline slides, is anyone aware of whether or not CIPLA is even still working on approval of inhaled insulin? Any thoughts? That's a really good question. Mike has mentioned several times he was expecting 1.5 - 2.0% A1c reduction from the Cipla trial. If for some reason the Cipla relationship has fallen apart Mike will have some real explaining to do. He also should be working on putting his own large scale T2 trial together. Maybe mum's the word with Cipla right now and they will be announcing great news soon. Lets hope. - Ha! Could you imagine great news from MNKD! |
|
|
|
Post by akemp3000 on Jan 22, 2024 7:54:51 GMT -5
Continue with treat to failure SOC or give beta cells the opportunity to recover?
|
|
|
|
Post by prcgorman2 on Jan 22, 2024 8:27:29 GMT -5
Why is India duplicating a trial already done? Great question. Cipla trial was because the India equivalent of the FDA chose not to approve Afrezza based on the FDA approval and required Cipla to run a trial. That was well pre-COVID. The lack of mention of the India trial by MNKD is not encouraging. The results might have been great, but trial design of question or generally not persuasive in the US and Cipla may have exclusive rights to the data and disinclined to share without compensation. No idea, but India has yet to be a boon to MNKD and it’s been years. Same situation for Brazil, Australia, et cetera. It hurts because I know Sanofi had the ability and resources to do world-wide marketing. Mike has said more than once they would be open to an extra-US world-wide marketing agreement, but few companies are candidates. And so Afrezza remains constrained. Tragic, but not Mike’s fault. If Afrezza sales are a marketing failure than full-scale multi-arm studies are a marketing requirement and they’re not cheap or fast (aka “risky” generally speaking). I still hope MNKD remains resolute and takes on that level of “marketing” as soon as practicable and I trust the Board and management to do that as money permits. If MNKD really does manage something approaching debt-free (or debt on non-toxic terms), things could get very interesting for Afrezza. That’s years away still I think, although Bill McCullough is giving me hope it may not be as bleak as all that. |
|
|
|
Post by agedhippie on Jan 22, 2024 8:45:05 GMT -5
... Let me ask you a question - you said - " Mounjaro fixes the underlying problem of insulin sensitivity and takes no work by the person using it" ... Most likely to succeed in reducing A1c with minimal effort and potentially no lifestyle change? Mounjaro." Why is it as Mike has mentioned numerous times that maybe Mounjaro works for 2 years and then the numbers start to rise again? ... Since that's Mike's statement you are asking the wrong person the question, you should be asking Mike. You are misquoting Mike, he was talking about GLP-1 and not Mounjaro (GLP-1/GIP). Besides, Mounjaro has not been out for two years. My feeling is that I trust what Bill or Stevil are actually seeing in patients that they treat as opposed to Mike. |
|
|
|
Post by agedhippie on Jan 22, 2024 8:49:58 GMT -5
Continue with treat to failure SOC or give beta cells the opportunity to recover? Anything that reduces glucose levels gives the beta cells the opportunity to recover, for example weight loss. Beta cell recovery is distinct from progression of the disease. |
|
|
|
Post by sayhey24 on Jan 22, 2024 9:52:06 GMT -5
... Let me ask you a question - you said - " Mounjaro fixes the underlying problem of insulin sensitivity and takes no work by the person using it" ... Most likely to succeed in reducing A1c with minimal effort and potentially no lifestyle change? Mounjaro." Why is it as Mike has mentioned numerous times that maybe Mounjaro works for 2 years and then the numbers start to rise again? ... Since that's Mike's statement you are asking the wrong person the question, you should be asking Mike. You are misquoting Mike, he was talking about GLP-1 and not Mounjaro (GLP-1/GIP). Besides, Mounjaro has not been out for two years. My feeling is that I trust what Bill or Stevil are actually seeing in patients that they treat as opposed to Mike. I am not sure what you are saying. Mike was not talking GLP1s, he was talking about the 1.5 - 2% A1c reduction as a result of using afrezza he had been briefed on from the Cipla trial. His comment was this 1.5 - 2% reduction is the same reduction GLP1s were touting. I will add, if true and GLP1s are now step 2 in the SoC, afrezza too should be added here. Of course thats the last thing BP wants and goes back to me being the broken record for why MNKD needs to dramatically grow the afrezza patient base over the next 2 years. BTW - Whats Mounjaro touting and if you think it will continue to show improved results past 2 years you will be disappointed. Bill has a well defined protocol which has been refined over the last 7 years. Bill's biggest problem is afrezza cost. I would be very surprised if Mike is not aware of what Bill has been doing and the success he has seen. Bill has probably annoyed the hell out of Mike trying to get more free samples. However, I doubt Bill has any insight into the Cipla results. We know Mike does. |
|
|
|
Post by agedhippie on Jan 22, 2024 16:32:22 GMT -5
Since that's Mike's statement you are asking the wrong person the question, you should be asking Mike. You are misquoting Mike, he was talking about GLP-1 and not Mounjaro (GLP-1/GIP). Besides, Mounjaro has not been out for two years. My feeling is that I trust what Bill or Stevil are actually seeing in patients that they treat as opposed to Mike. I am not sure what you are saying. ... [And then some irrelevant stuff about CIPLA and not Mounjaro at all]Let's try this again then. Your question to Stevil that I responded to was "Why is it as Mike has mentioned numerous times that maybe Mounjaro works for 2 years and then the numbers start to rise again?" Mike was talking about GLP-1 and never mentions Mounjaro - source: 3rd earnings call responding to a question. The exact quote is, "My guess is GLPs are going to push this off a year or two." |
|
|
|
Post by sayhey24 on Jan 22, 2024 18:00:14 GMT -5
I am not sure what you are saying. ... [And then some irrelevant stuff about CIPLA and not Mounjaro at all]Let's try this again then. Your question to Stevil that I responded to was "Why is it as Mike has mentioned numerous times that maybe Mounjaro works for 2 years and then the numbers start to rise again?" Mike was talking about GLP-1 and never mentions Mounjaro - source: 3rd earnings call responding to a question. The exact quote is, "My guess is GLPs are going to push this off a year or two." OK - I was wrong. He did not say 2 years but rather "a year or two". Are you trying to split hairs and are trying to make some argument the gip component is going to dramatically change things? Come on man! As I said above if you think Mounjaro is going to provide benefit after two years think again. If you understood how this is actually working and what is going on its obvious. Just keep hanging on that afrezza is not the best solution for T2 diabetes and get on Ralphie's train. I will stay on Al's. Then again I have not heard much from Ralph lately. I think my last email to him pissed him off. For some reason I think Ralph just may think Al was right after all. Then again BP has big $$$ for the "thought leaders" and money talks. Maybe Mike should show up with his checkbook. Could you imagine Ralph becoming the afrezza spokesman. I think that would make Al smile. |
|
|
|
Post by radgray68 on Jan 22, 2024 18:19:48 GMT -5
Could we be in the process of negotiating with Cipla now that the trial results are in? That would require us to be mum
|
|
|
|
Post by sayhey24 on Jan 22, 2024 18:23:11 GMT -5
Maybe - that had crossed my mind. Lets hope so and the results are great.
|
|
|
|
Post by stevil on Jan 22, 2024 20:50:44 GMT -5
I’m not so certain that giving people with diabetes insulin as the first step is “medically correct” yet. That cannot be stated as fact yet.
I often order fasting insulin on my obese/prediabetic patients to see how big their risk factor is of getting diabetes. Way more often than not, they’re not at an insulin deficit but they actually have hyperinsulinemia. This was talked about in the podcast I linked.
You could actually make the argument that targeting insulin sensitivity/resistance is actually “medically correct” since that’s actually the underlying problem, not an insulin deficit.
It’s actually not harmless to have people running around with excess insulin. Insulin is pro-inflammatory in excess (although, to be fair this is seen much more with long-acting insulin, maybe not Afrezza. However, a precedent has been set between the effects of exposure to insulin and inflammation).
All that to say- I’m not disagreeing with Bill, per se. I just don’t think anyone can say with certainty that the SOC is completely wrong and AFALAA is the for sure correct step. I think the SOC paints the general population with a broad brush instead of a more nuanced approach. I think as more is learned about diabetes, more individualized treatment will eventually emerge. I think the SOC will work for most and AFALAA will be better for some as well. I have some patients stable on metformin for 30 years. Others that rapidly progress in 3-5 years without insulin antibodies and don’t have LADA.
If Bill believes he has the answer, he absolutely should set out to prove it. Man(n)kind needs him to. Despite how some might read my thoughts, I actually view myself as an ally and friend to him and he was more than gracious to share his thoughts with me when I was first starting to use Afrezza. I just don’t share the same convictions… yet.
Type 2 diabetes hardly existed 50 years ago. It wasn’t a virus that increased incidence. It’s an unhealthy lifestyle. Humans used to need to do work to live. Now we sit and drive around in cars. We used to have a perpetual food shortage (unless you were royalty), now we all eat like kings with access to refined, ultraprocessed, calorie dense foods that lack the necessary fiber to tell our brains we’re not hungry. Our intestinal flora is disrupted as well as good bacteria cannot thrive when eating garbage for food.
As I have stated before, we should be clamoring to change the food pyramid and being advocates for exercise. I suspect a lot of people on this board may not feel as strongly about Afrezza if they were not invested in MNKD, or at least might have different priorities/viewpoints in this debate.
|
|
|
|
Post by sayhey24 on Jan 22, 2024 23:01:36 GMT -5
I’m not so certain that giving people with diabetes insulin as the first step is “medically correct” yet. That cannot be stated as fact yet. I often order fasting insulin on my obese/prediabetic patients to see how big their risk factor is of getting diabetes. Way more often than not, they’re not at an insulin deficit but they actually have hyperinsulinemia. This was talked about in the podcast I linked. You could actually make the argument that targeting insulin sensitivity/resistance is actually “medically correct” since that’s actually the underlying problem, not an insulin deficit. It’s actually not harmless to have people running around with excess insulin. Insulin is pro-inflammatory in excess. All that to say- I’m not disagreeing with Bill, per se. I just don’t think anyone can say with certainty that the SOC is completely wrong and AFALAA is the for sure correct step. I think the SOC paints the general population with a broad brush instead of a more nuanced approach. I think as more is learned about diabetes, more individualized treatment will eventually emerge. I think the SOC will work for most and AFALAA will be better for some as well. I have some patients stable on metformin for 30 years. Others that rapidly progress in 3-5 years without insulin antibodies and don’t have LADA. If Bill believes he has the answer, he absolutely should set out to prove it. Man(n)kind needs him to. Despite how some might read my thoughts, I actually view myself as an ally and friend to him and he was more than gracious to share his thoughts with me when I was first starting to use Afrezza. I just don’t share the same convictions… yet. Type 2 diabetes hardly existed 50 years ago. It wasn’t a virus that increased incidence. It’s an unhealthy lifestyle. Humans used to need to do work to live. Now we sit and drive around in cars. We used to have a perpetual food shortage (unless you were royalty), now we all eat like kings with access to refined, ultraprocessed, calorie dense foods that lack the necessary fiber to tell our brains we’re not hungry. Our intestinal flora is disrupted as well as good bacteria cannot thrive when eating garbage for food. As I have stated before, we should be clamoring to change the food pyramid and being advocates for exercise. I suspect a lot of people on this board may not feel as strongly about Afrezza if they were not invested in MNKD, or at least might have different priorities/viewpoints in this debate. Stevil - Man, I don't know where to start. Let me start here "I just don’t think anyone can say with certainty that the SOC is completely wrong". Didn't I give you the quote from the guy who strong armed metformin through the FDA? What is step 1, not step 2 or 3 but step 1 in the SoC? The last I looked it was metformin. What did Ralph say? I know he said it is the GREATEST waste of time in diabetes care. That is step 1. The SoC is completely wrong - COMPLETELY!!! Then you say T2 diabetes hardly existed 50 years ago? My mom's mom was a T2. My father died of a massive heart attack due to T2. He did not drink. He did not smoke and he ate his vegetables. Where did you get the crazy idea T2 did not exist 50 years ago. My grandmother died after a stroke at age 63. You can keep telling yourself T2 diabetes did not increase during covid - but some others think differently. This group thinks by 60% www.ncbi.nlm.nih.gov/pmc/articles/PMC10244847/#:~:text=Recent%20Findings,general%20morbidity%20after%20respiratory%20illness. You can believe what you want but if its all about being fat and eating bad, why don't most obese people have diabetes? About 80% of obese do not have diabetes. Why??? What happens when you autopsy their pancreases??? Yes, they grow more beta cells. Big clumps in fact. As far as Bill, he proves his protocal every day. It works. Bill has developed his own SoC which medically treats patients properly. Why you don't want to believe what VDex is doing works, I don't know nor do I care. Bill does not need to prove anything. He already has. What he needs is affordable afrezza. He needs afrezza at a cost his patients can afford. The reality is Bill did not come up with this idea. Al Mann did. What Bill did was listen and then implement. I suspect Bill heard Al say something like this "Well, that is medically incorrect. Starting a type 2 on basal insulin is done today because current prandial insulin products are not physically sound so they are delayed about as long as they can be. Lantus has been so successful as the first insulin used in type 2 because of the problems with current prandial products." www.diabetesincontrol.com/an-exclusive-interview-with-al-mann-founder-and-ceo-mannkind-corp/Al also said and I suspect Bill heard "In early Type 2, a variety of alternative antiglycemic drugs are used today and these products are viable largely because of the deficiencies of current insulin products. But it is insulin that the body needs for glucose metabolism. Even with the limitations of current insulin products, there is increasing pressure to move patients much sooner to exogenous insulin. The alternative antiglycemic products are intended simply to supplement endogenous pancreatic insulin more effectively. Some of them are directed to increasing pancreatic output, likely contributing to early-year beta cell burnout. Other products have tested lower resistance to insulin to inhibit hepatic glucose release or to slow digestion, but all of these drugs have limited efficacy and side effects that can be significant in some patients and the long-term safety for many of them may still be in doubt. Moreover, none of these antiglycemics, I believe, does slow progression of the disease so that, after 8 to 12 years, patients using those drugs typically move on to insulins. Another issue is that many of the newer, more advanced antiglycemic agents are very expensive. If only there were a physiologic ultra-fast-acting insulin that would reduce postprandial hyperglycemia to within normal guidelines without the risk of hypoglycemia or weight gain and without the complexity of titration or the need for multiple daily measurements of glucose. Such a prandial insulin would far better deal with postprandial excursions throughout the entire spectrum of diabetes. Moreover, key opinion leaders assert that, by reducing pancreatic and hepatic stress, such an insulin would slow and perhaps even stop progression of Type 2 diabetes and prediabetes. Surely, that would seem to offer a far better solution than those alternative drugs. Moreover, a therapy that does not require the inconvenience and discomfort of multiple daily injections, would certainly be more patient-friendly. AFREZZA has been shown in over 50 clinical trials to mimic endogenous insulin kinetics and this should enable this insulin to more effectively and more safely address the objectives of providing improved glycemic control. A product such as AFREZZA would be especially appealing to children and should ease the issues about treatment in the classroom. Because of the FDA's aversion about risk in this young population, the initial label for AFREZZA will be restricted to patients 18 years and older. The age -- asked us [ph] to submit a post-approval Phase IV protocol for a trial in children. We responded with a proposed study in children ages 12 to 18. Interestingly, FDA directed us to include children down to age 4." Read more: mnkd.proboards.com/thread/8725/remember-al-said#ixzz4v3r43fKP |
|
|
|
Post by stevil on Jan 22, 2024 23:20:54 GMT -5
external-content.duckduckgo.com/iu/?u=https%3A%2F%2Ftse1.mm.bing.net%2Fth%3Fid%3DOIP.dB_YbeZi5rZ-z90PDEqeIAHaG6%26pid%3DApi&f=1&ipt=81314e796654bf4d89c231cc3486cf676a90ec214d8ba89fc216258ee560109d&ipo=imagesI don’t really care to refute every “point” you make because you constantly live in a world where sound, proven research is inaccurate because it doesn’t fit your narrative. Viruses have been around as long as humans have- they just now started to cause diabetes?! You can’t even use international travel as an excuse because there should be pockets of people in the past that had these viruses plaguing them before they airplanes made their diseases rampant. I’ll save you the trouble- they don’t exist. Then, how do you explain how low income people suffer most from diabetes? Must be the viruses only target them, ignoring the fact they don’t eat high quality food and are most prone to stressful lives and a high content of fast and cheap, processed foods. Looking at the linked graph… you really want to look at that graph and say a virus that came out in 2020 caused that slope?! I usually don’t like to argue like this because correlation does not equal causation, but tell me if this graph looks anything like the link above- cause they look awfully similar to me. external-content.duckduckgo.com/iu/?u=https%3A%2F%2Fupload.wikimedia.org%2Fwikipedia%2Fcommons%2Fthumb%2Ff%2Ffc%2FObesity_in_the_United_States.svg%2F1200px-Obesity_in_the_United_States.svg.png&f=1&nofb=1&ipt=7a4c2d107505660bee2809870dfd6f4e0f11f25c0130eabfb20cce7af9899cc0&ipo=imagesBtw, I never said obesity causes diabetes. I have patients with BMI over 50 with an A1c of 4.8. Not everyone gets it. In fact, this is probably even better proof that your virus theory is wrong- if it was caused by a virus, that guy was just lucky enough to have dodged it?! What about the other 250 million Americans that don’t have diabetes from COVID? There’s a genetic link and predisposition to diabetes. It’s probably why it runs in your family. Unless your family never came in contact with anyone else, why were they the only ones that got it? I think there are probably some people who get viral illnesses and then develop diabetes. These people probably have LADA and make up a very small subset of diabetes. But just in the way not all smokers get lung cancer, not all people that are obese get diabetes. There is a whole new field of epigenetics that look into this. I’d recommend doing some reading… I will admit I don’t fact check every source that I have been taught. I trust my medical education and I try my best to eliminate biases, intentional or otherwise, from the data I do look at. I’ve said about all I can say on this. I don’t really care to go line by line refuting you because as aged has said many times, your basic science is often way off and you don’t ever back down from your stances. I’ll spare others the grief of the constant back and forth and save myself a few headaches as well. People will choose who they will believe. You will choose who and what you will believe. You can literally find research to support anything. Some people have even sought out to prove that smoking is good for your health and have “evidence “ so support it.
|
|
