Afrezza Lack of Awareness & Afrezza Learning Curve

[mango]

I saw a Reddit post in a diabetes subreddit from yesterday—it was by an Afrezza User asking about art ideas for their Afrezza cartridges he/she has been saving. In the comments 2 Reddit users posted about Afrezza. Below is the quotes by these 2 people:

1. “I learned something new today! I had no idea this cool inhalable insulin existed!

Thanks for sharing this OP!

Treat them like Legos and make a giant robot.”


2. “I have heard if afrezza years ago but never actually seen someone that uses it. Why isnt this a more used delivery method? Thats awesome”


There is 2 identifiable problems with Afrezza, we can call them the Afrezza Dilemma. The first, is the extreme lack of Afrezza awareness. I can’t just blame MannKind for this, I also blame ADA. ADA does nothing to promote awareness of this life changing, revolutionary insulin therapy. Is it because MannKind does not pay ADA?

Second, there is a serious Afrezza learning curve. Initial and early success with Afrezza seems to rely heavily on Afrezza coaching. We’ve really learned this through VDex. Prescribers can’t simply hand a script over and expect success. Patients often fail this in this regard. Afrezza requires careful coaching, and there is a steep learning curve.

A foreseeable problem I see here is if there was mass advertisement approach, and let’s pretend that over the course of a few months 98% of all PWDs became aware of Afrezza. Let’s pretend 40% of these people pursue Afrezza within 3 months of learning of it’s existence. Do we really expect physicians and NPs/PAs to all of a sudden prescribe Afrezza, much less spend the required time necessary coaching them on it? If people aren’t prescribing it currently then they more than likely don’t know enough about it to prescribe it properly and coach the new Afrezza User.

I feel like an overnight mass awareness could end up doing more harm than good because of the steep learning curve and apparent lack of willingness or time in schedule of prescribers to learn about Afrezza and teach it that majority would see poor results. Is the only way to force this willingness upon prescribers by changing the SoC?

How do we fix this Afrezza Dilemma? What are practical and scalable methodologies that can be deployed to solve one while simultaneously helping fix the other? Or will it require a multi-prong approach? I would say let’s build out a few thousand VDex locations but I’m not so sure that is realistic (but investment in VDex locations in every state per say could be). Any ideas?

[mytakeonit]

I believe that this question was directed to sports ... then, it goes to Bill. From what I've read before, it really sounds like VDEX is expanding into many states. When VDEX is in Hawaii ... then I'll know that the job is complete. (Or near complete due to the tiny populated states.)

But, that's mytakeonit

[sayhey24]

Mango - how many TV commercials have you seen for metformin? When do many (most) newly diagnosed T2's first hear of metformin? Why do GPs prescribe metformin?

Once the PWD gets afrezza the biggest issue (potential cough aside) they seem to have is under-dosing either on the initial dose or not doing follow-up dosing. The first thing which needs to be done here is a label change. IMO it should also having T1 "wording" and separate T2 "wording".

[stevil]

There has to be a benefit for any major shift in prescribing habits.

Metformin is first step because it is cheap, safe, and effective.

Sulfonylureas used to be second step but fell out of favor, despite being cheap, due to poor side effect profile, lack of cardiovascular/renal benefit, and hastening the progression of disease.

The only reason the newer/more expensive medications jumped the older/cheaper medications is because they showed better long term outcomes. Mannkind needs to pick some quantifiable and significant metric to target for their trials. I don't know where some on here get their information from because I don't think this would be that easy of a feat from the data I've reviewed. The bigger problem for mannkind is that any study of this type will take years- up to a decade or longer- to reap the rewards.

Currently, time in range hasn't shown a significant benefit to those not already on insulin. Hard sell there, although some extrapolations could be piggybacked off of other's work in the space since it is a popular new topic that is being studied.

I don't really see how Afrezza will lead to an improvement in cardiovascular and renal outcomes based off the data I have already reviewed. Everything I have read says otherwise - increased amounts of insulin actually increase both cardiovascular and renal disease since insulin is thought to increase inflammation and worsen coronary artery disease and it can be damaging to the kidneys as well, hastening renal disease. This information is based on previous studies of other insulins. However, since this data already exists, it will take more work to undo it for Afrezza, since it too is insulin.

The biggest problem Afrezza has is there isn't really any indication for early use unless someone's A1c is over 12 and that's only because you can then make the case for early intensive insulin treatment. But then you're right back into the standard of care once their A1c is controlled. With SGLT-2s and GLP-1s, you've got cardiovascular and renal benefits as well as weight loss on your side. Afrezza maybe will cause some weight loss, but for most will be weight neutral at best. Any benefit you'll get from Afrezza won't be realized for over a decade and the clock hasn't even started on collecting that data.

I'm ambivalent to Mike. I don't know enough to know whether he is brilliant or rotten at his job. I do, however, see how difficult it is to navigate Afrezza through the mess of healthcare. As much as I hate the idea of sitting back and doing nothing, it's really the only option the company has right now as long as it will require a substantial investment that won't realize a return for many years down the line. Their best hope is that time in range studies will be completed by CGMs and prove to be significant.

Afrezza will likely never be first step in any standard of care. By the time they would be, there will probably be a cure or a near cure that will restore beta function. I say this as someone that definitely has more shares than I should in the company. I gave up on Afrezza a long time ago. It's going to be the rest of the pipeline that carries the company going forward. Afrezza will continue to grow slowly over time and remain a niche product for the reasons I mentioned above. I don't expect it to be a popular opinion, but I believe it's one that is pretty sound according to the data that is widely available from respectable sources.

[akemp3000]

Certainly an interesting perspective. It brings to mind the opposite perspective of a former Chief Scientific Officer of the American Diabetes Association calling Metformin and the current standard of care for diabetes antiquated, barbaric and ineffective!

[stevil]

And what did he accomplish after saying those words? That, to me, is more interesting.

[buyitonsale]

Afrezza is the most effective mealtime insulin on the market.

This type of an ultra fast acting insulin is intended for diabetics that have no more than 3 discreet meals per day, because they understand time in range significance. Usually, only T1D patients think this way and in those cases, Afrezza has the best chance for mass adoption.

Most type 2 diabetics do not understand how they got here (hyperinsulinemia and insulin resistance), nor the concept of 3 discreet meals a day. Instead, anything goes (including snacks and soft drinks all day).

T2D patients first need to be educated about the root cause of their "disease" and then asked if they are willing to make necessary changes to reverse it. Those patients that will assume the responsibility of restoring their own health, are most likely to adopt Afrezza on that journey. Others, will continue to have same outcomes, regardless of what is prescribed.

[akemp3000]

Sept 28, 2022 0:18:12 GMT -5 stevil said:

And what did he accomplish after saying those words? That, to me, is more interesting.

Switching the topic doesn't discredit his accomplishment in becoming the Chief Scientific Officer of the American Diabetes Association. He has credibility.

[sr71]

Sept 27, 2022 22:42:35 GMT -5 stevil said:

There has to be a benefit for any major shift in prescribing habits.

Metformin is first step because it is cheap, safe, and effective.

Sulfonylureas used to be second step but fell out of favor, despite being cheap, due to poor side effect profile, lack of cardiovascular/renal benefit, and hastening the progression of disease.

The only reason the newer/more expensive medications jumped the older/cheaper medications is because they showed better long term outcomes. Mannkind needs to pick some quantifiable and significant metric to target for their trials. I don't know where some on here get their information from because I don't think this would be that easy of a feat from the data I've reviewed. The bigger problem for mannkind is that any study of this type will take years- up to a decade or longer- to reap the rewards.

Currently, time in range hasn't shown a significant benefit to those not already on insulin. Hard sell there, although some extrapolations could be piggybacked off of other's work in the space since it is a popular new topic that is being studied.

I don't really see how Afrezza will lead to an improvement in cardiovascular and renal outcomes based off the data I have already reviewed. Everything I have read says otherwise - increased amounts of insulin actually increase both cardiovascular and renal disease since insulin is thought to increase inflammation and worsen coronary artery disease and it can be damaging to the kidneys as well, hastening renal disease. This information is based on previous studies of other insulins. However, since this data already exists, it will take more work to undo it for Afrezza, since it too is insulin.

The biggest problem Afrezza has is there isn't really any indication for early use unless someone's A1c is over 12 and that's only because you can then make the case for early intensive insulin treatment. But then you're right back into the standard of care once their A1c is controlled. With SGLT-2s and GLP-1s, you've got cardiovascular and renal benefits as well as weight loss on your side. Afrezza maybe will cause some weight loss, but for most will be weight neutral at best. Any benefit you'll get from Afrezza won't be realized for over a decade and the clock hasn't even started on collecting that data.

I'm ambivalent to Mike. I don't know enough to know whether he is brilliant or rotten at his job. I do, however, see how difficult it is to navigate Afrezza through the mess of healthcare. As much as I hate the idea of sitting back and doing nothing, it's really the only option the company has right now as long as it will require a substantial investment that won't realize a return for many years down the line. Their best hope is that time in range studies will be completed by CGMs and prove to be significant.

Afrezza will likely never be first step in any standard of care. By the time they would be, there will probably be a cure or a near cure that will restore beta function. I say this as someone that definitely has more shares than I should in the company. I gave up on Afrezza a long time ago. It's going to be the rest of the pipeline that carries the company going forward. Afrezza will continue to grow slowly over time and remain a niche product for the reasons I mentioned above. I don't expect it to be a popular opinion, but I believe it's one that is pretty sound according to the data that is widely available from respectable sources.

Stevil -

I mean no disrespect, but I do not agree with the implication that Afrezza may/will "increase inflammation and worsen coronary artery disease and it can be damaging to the kidneys as well".  While it could be possible that injectable insulin may have those effects, we must keep in mind that those products are in the hexameric form, so are fundamentally different from (monomeric) Afrezza which structurally and functionally closely mirrors the natural insulin produced by our bodies.

Therefore, if Afrezza were to cause the negative effects you mentioned, then that is tantamount to saying that non-diabetics are being damaged by the natural insulin produced by their own bodies, which of course is not true.

[sweedee79]

Stevil isnt saying that Afrezza would cause harm to the kidneys... He is saying we don't have data to prove that Afrezza is as good as we all know it is... He is also stating an opinion from the perspective of a physician..

We have had problems with physicians not wanting to prescribe.. IMO this explains the dilemma.. and we should listen..

It isn't that Afrezza isn't as good as we all know it is.... We simply don't have the large scale trial data to prove it.. If Kendall could have he would have..

[stevil]

Sept 28, 2022 8:17:13 GMT -5 akemp3000 said:

Sept 28, 2022 0:18:12 GMT -5 stevil said:

And what did he accomplish after saying those words? That, to me, is more interesting.

Switching the topic doesn't discredit his accomplishment in becoming the Chief Scientific Officer of the American Diabetes Association. He has credibility.

I wasn't changing the topic. I was supporting my assertion that nothing is going to change in the type 2 space regarding Afrezza. Kendall wasn't able to get anything done despite his thoughts and convictions about how great Afrezza is.

[stevil]

Sept 28, 2022 9:02:40 GMT -5 sr71 said:

Sept 27, 2022 22:42:35 GMT -5 stevil said:

There has to be a benefit for any major shift in prescribing habits.

Metformin is first step because it is cheap, safe, and effective.

Sulfonylureas used to be second step but fell out of favor, despite being cheap, due to poor side effect profile, lack of cardiovascular/renal benefit, and hastening the progression of disease.

The only reason the newer/more expensive medications jumped the older/cheaper medications is because they showed better long term outcomes. Mannkind needs to pick some quantifiable and significant metric to target for their trials. I don't know where some on here get their information from because I don't think this would be that easy of a feat from the data I've reviewed. The bigger problem for mannkind is that any study of this type will take years- up to a decade or longer- to reap the rewards.

Currently, time in range hasn't shown a significant benefit to those not already on insulin. Hard sell there, although some extrapolations could be piggybacked off of other's work in the space since it is a popular new topic that is being studied.

I don't really see how Afrezza will lead to an improvement in cardiovascular and renal outcomes based off the data I have already reviewed. Everything I have read says otherwise - increased amounts of insulin actually increase both cardiovascular and renal disease since insulin is thought to increase inflammation and worsen coronary artery disease and it can be damaging to the kidneys as well, hastening renal disease. This information is based on previous studies of other insulins. However, since this data already exists, it will take more work to undo it for Afrezza, since it too is insulin.

The biggest problem Afrezza has is there isn't really any indication for early use unless someone's A1c is over 12 and that's only because you can then make the case for early intensive insulin treatment. But then you're right back into the standard of care once their A1c is controlled. With SGLT-2s and GLP-1s, you've got cardiovascular and renal benefits as well as weight loss on your side. Afrezza maybe will cause some weight loss, but for most will be weight neutral at best. Any benefit you'll get from Afrezza won't be realized for over a decade and the clock hasn't even started on collecting that data.

I'm ambivalent to Mike. I don't know enough to know whether he is brilliant or rotten at his job. I do, however, see how difficult it is to navigate Afrezza through the mess of healthcare. As much as I hate the idea of sitting back and doing nothing, it's really the only option the company has right now as long as it will require a substantial investment that won't realize a return for many years down the line. Their best hope is that time in range studies will be completed by CGMs and prove to be significant.

Afrezza will likely never be first step in any standard of care. By the time they would be, there will probably be a cure or a near cure that will restore beta function. I say this as someone that definitely has more shares than I should in the company. I gave up on Afrezza a long time ago. It's going to be the rest of the pipeline that carries the company going forward. Afrezza will continue to grow slowly over time and remain a niche product for the reasons I mentioned above. I don't expect it to be a popular opinion, but I believe it's one that is pretty sound according to the data that is widely available from respectable sources.

Stevil -

I mean no disrespect, but I do not agree with the implication that Afrezza may/will "increase inflammation and worsen coronary artery disease and it can be damaging to the kidneys as well".  While it could be possible that injectable insulin may have those effects, we must keep in mind that those products are in the hexameric form, so are fundamentally different from (monomeric) Afrezza which structurally and functionally closely mirrors the natural insulin produced by our bodies.

Therefore, if Afrezza were to cause the negative effects you mentioned, then that is tantamount to saying that non-diabetics are being damaged by the natural insulin produced by their own bodies, which of course is not true.

Except it is true. It's exactly their own insulin that is believed to cause the inflammation and increased risk of heart attack and stroke from diabetes. Despite what has been said here, there exists a state of hyperinsulinemia (in the monomeric form, mind you) due to believed insulin resistance.

This is the part that is so hard to explain to people that haven't been educated to see the big picture and thus thinks the solution is much simpler than it actually is. Diabetes (type 2) is not simply a disease of insulin deficiency. There are so many other known mechanisms that are impaired that affect the release and absorption of insulin. The body's natural response, when beta cell function is still intact, is to do just what you all are recommending - increasing serum insulin. This is known to cause albuminuria, which then increases kidney disease. An increase in insulin is also believed to cause inflammation of arteries (along with AGEs), which would then lead to cholesterol formation and plaque deposition= stenosis.

Again, this is current theory of insulin and why I believe it is going to be an incredibly challenging uphill battle for Afrezza to have a significant role in early type 2 treatment outside of early intensive treatment. I have been following VDex's work closely because while I want desperately for the thoughts and opinions on this board to be true, the data has not born out the same conclusions... Yet. It's going to take a tremendous amount of work to reverse what is already believed to be known if indeed different outcomes are achieved with Afrezza.

Sweedee is correct, I am not all of your enemies. The answer just isn't as simple as it appears to be. Until different data appears that conflicts with what is already known, Afrezza will remain one of the last steps of treatment in the standard of care. Not even I (as a self-proclaimed Afrezza enthusiast) am convinced it should be otherwise, which is why I remain so interested in VDex's work. I'm hopeful that their patients do have better long-term outcomes and that they're able to publish those results for us all to see.

[cretin11]

Thanks stevil for shooting straight with us, even (and especially) when your info is not popular here. Some of us would rather hear truth than spin.

[sayhey24]

Sept 28, 2022 10:49:11 GMT -5 stevil said:

Sept 28, 2022 8:17:13 GMT -5 akemp3000 said:

Switching the topic doesn't discredit his accomplishment in becoming the Chief Scientific Officer of the American Diabetes Association. He has credibility.

I wasn't changing the topic. I was supporting my assertion that nothing is going to change in the type 2 space regarding Afrezza. Kendall wasn't able to get anything done despite his thoughts and convictions about how great Afrezza is.

Wow!  Nothing is going to change in the T2 space.  Man, I really hope you are dead wrong.  Right now we have a treat to fail protocol.  Are you telling me we can not do any better?  We have a guy name Richard Bernstein who has  blazed a trail showing us that by reducing post prandial spikes and good overall BG control we can avoid the typical vascular damage most diabetic encounter.  Maybe we can learn from that?

Above you say "There has to be a benefit for any major shift in prescribing habits."  How about stopping T2 progression and maybe even reversing it.  I think that would be a significant benefit.

Then you say "Metformin is first step because it is cheap, safe, and effective."  Its clearly cheap.  We know its not effective or we would not see all these T2s progress to step 2 in the treat to fail protocol.  What does Ralph DeFranzo say about metformin - its a waste of time an dangerous because it delays saving the beta cells?  diatribe.org/the-diatribe-foundation-and-tcoyd-11th-annual-forum 


BTW - things like Orinase and Diabinese use to be step 1 not step 2.  They were the SGLT2s and GLP1 of their day and were hailed as miracle drugs.   What a mess they made.


Then you say "The only reason the newer/more expensive medications jumped the older/cheaper medications is because they showed better long term outcomes."  What better long term outcomes?  For starters most GLP1 users are only on it for about 6 months and by 2 years nearly all stop.  Does pissing out sugar at 180mg/dl make any sense letting the PWD in hyperglycemia in a permanent condition? 

Then you say "time in range hasn't shown a significant benefit to those not already on insulin."  Define your TIR upper limit.  The magic number seems to be 140mg/dl.  What we know is non-diabetics don't usually go over it but never stay over it for more than 2 hours.  We also know staying in a hyperglycemic state >140mg/dl  causes all kinds of issues.  Here is one such discussion on the topic. ncbi.nlm.nih.gov/pmc/articles/PMC6352876

Now - if you don't see how controlling the post meal spike and getting it down under 140 in less than two hours will lead to an improvement in cardiovascular and renal outcomes based off the data you have already reviewed I think you need to look at some other data.   The problem is the community does not want to set the upper TIR limit at 140 so finding study data on this will be thin.  Doing this prior to afrezza would be dangerous.  In fact a doctor at the Adcom when talking on a similar topic said he would have killed his patients if second dosing with an RAA and keeping a tight range.  As a thought give Rich Bernstein a call and get his opinion.  His office number is [phone]. This guy has been mimicking what afrezza will do for BG control longer than anyone but he has been doing it the hard way. However, the results will be the same. 

[agedhippie]

Sept 28, 2022 15:50:16 GMT -5 sayhey24 said:

Sept 28, 2022 10:49:11 GMT -5 stevil said:

I wasn't changing the topic. I was supporting my assertion that nothing is going to change in the type 2 space regarding Afrezza. Kendall wasn't able to get anything done despite his thoughts and convictions about how great Afrezza is.

Wow!  Nothing is going to change in the T2 space.  Man, I really hope you are dead wrong.  Right now we have a treat to fail protocol.  Are you telling me we can not do any better?  We have a guy name Richard Bernstein who has  blazed a trail showing us that by reducing post prandial spikes and good overall BG control we can avoid the typical vascular damage most diabetic encounter.  Maybe we can learn from that?...

I had a whole long reply, but it essential boils down to saying that without large scale trial data showing that Afrezza materially improves outcomes over the long term then this is all just theories and nobody is going to move. Yes, there will be change in the T2 space but that change is not going to be insulin, it's going to be incretin mimetics like GLP-1. Even so the first line will remain metformin because it buys a few years and is cheap.

The issue for Afrezza is that there is no data quantifying the degree to which Afrezza gives better long term outcomes. This is not true for GLP-1 drugs which have extensive data. Without that data you are basically saying "trust me, it should work better" and that is never going to be a winner with the broader medical community who like certainty (and as a patient so do I!) It may be that logically you would expect it to do better, but trials are littered with cases where that has not proven to be true.

In fact a doctor at the Adcom when talking on a similar topic said he would have killed his patients if second dosing with an RAA and keeping a tight range.

That doctor is an idiot, it's called a correction and you do them when you get the first one wrong. I would advise his patients to find a new endo. It's a good example of the issues diabetics have with endos though. To an extent with AID pumps it's moot these days as the pumps do all of that for you automatically.