MannKind: Afrezza Is Blooming With Scientific Chatter

[agedhippie]

Jun 7, 2018 12:36:48 GMT -5 peppy said:

Jun 7, 2018 9:54:28 GMT -5 agedhippie said:

It could, but the problem is the statistical significance. It is within the margin of error so the results could actually be reversed. Think of it like an opinion poll where the two candidates are withing the margin of error - one of them is going to win, but statistically it could have be either. If I was presenting the results I would give the chart with minimal commentary and let people draw their own (possibly incorrect) conclusion that Afrezza will reliably cause fewer hypos.

While an endo will find the result interesting what they will want to see is the underlying data. Specifically were all those hypos from one person or were they spread through a group? The first case would make them discount the results, the second answer would give more credibility to the results. As an example Al said that most of the hypos in the Type 2 trial were due to one or two people which means the results were better than they looked.

JARDIANCE is the only type 2 diabetes pill proven to go beyond lowering A1C to reduce the risk of CV death for adults who have type 2 diabetes and heart disease.
www.jardiance.com/?sc=JARACQWEBSEMGGL1408001&utm_source=google&utm_medium=cpc&utm_term=jardiance&utm_campaign=Branded_-_Jardiance_-_BMM&gclid=CjwKCAjwr-PYBRB8EiwALtjbz50IIQ-d2B4nfs8hy6427bUf34gIr9oOmPUMyRe1c1H2TRat6in-7xoCAF8QAvD_BwE&gclsrc=aw.ds

The Jardiance commercial saids proven to reduce CV death.
The black box warning saids, amputation, bone fractures, infections. Help me out here. What is the statistical significance here? The commercial does not say amputation. it saids decreased blood volume. 

I think it is almost impossible to get a black box warn without a statistical significant finding.

The black box warning is for Invokana (canagliflozin). There is no black box warning for Jardiance (Empagliflozin).

The question is whether this is a side effect of Invokana, or of the whole class of SGLT2 family. Right now the balance of evidence is that it is Invokana specific and that Jardiance does not increases amputations. What they did was review all participants medical records in the EMPA-Reg Outcome trial for amputations and found no increase. This was done by review rather than report (there was no specific report class for amputations), but the methodology looks solid and since this was a 7000+ patient trial errors should cancel out (link to paper here). 

The class action lawyers were rather hoping amputation is a class effect affecting all SGLT2 drugs but based on the evidence this looks like a drug specific side effect. Hence no black box and no warnings in adverts in Jardiance adverts.

[sayhey24]

Aged - while I understand why you said the following, as Al would say "its medically incorrect"

You said - "you use the same amount of basal insulin if your baseline is 100 or 300. If you are flat at 200 on basal only and want to be flat at 150 then you correct with prandial insulin to get to 150, you do not increase your basal to do that. Basal insulin is there to cover basal glucose and basal glucose is constant day to day. I know this is how it works because it was what I was taught to do"

There was a really good interview with Al on this but I can't find the link. While I look for it think about what happens in a non-diabetic. Assume 85 as your fasting baseline - what keeps you at that? The amount of insulin released by the pancreas during fasting. If you could control your pancreas and wanted to be at 80 - what would you do? Yes, have the pancreas release more insulin during fasting.

In both cases first and second release during meals will bring you back to your baseline which could be the 80 or 85. Once you start going below your baseline the alpha cell's will wake up, signal the liver and will start releasing sugar.

I understand why you were taught to control your baseline with your prandial and not your basal. Simply said both your basal and prandial were not capable of replicating natural insulin release. Your basal could not properly regulate your fasting periods. More at issue is your prandial is a mess and all over the place. You never stop the spike, you go high, then you go low and once the out of control elevator stops its anyone's guess what floor its going to stop on.

However, the medically correct approach is to have you understand what your target baseline is and control it with the basal. Then use the prandial to stop the spike and bring you back to baseline in about 2 hours. This is the way the body works.

Its also the hurdle Mike faces in trying to sell afrezza. All the diabetes experts want to put afrezza in the "Insulin Box". We have always been taught to control A1c with our prandial, right? If you have a hammer and a screwdriver but the head keeps flying off the hammer, use the handle of the screwdriver to pound the nail. Good Grief! Everyone knows insulin is dangerous. It has needles. Its a mess. Yes, afrezza has been placed in the box and Mike needs to get it out of the box.

The great new is afrezza is not insulin as we all know insulin. The BAD news is everyone knows afrezza as insulin. If they just knew it as a "Super Powder" it would be the "Next Gen" class of anti-glycemic - the GSP class (Glucose Super Powder). Afrezza has the ability to truly mimics how the body works during first and second phase release. For the T2 its really easy, just take enough afrezza to get you back to baseline in 2 hours, If you take a little too much, no problem as the liver will kick in. For the T1 on the AP just take the afrezza with a bit more care to get you to baseline and the AP will use the RAA as the basal to keep you flat. For the rest of the T1s Tresiba seems to be the winner for most.

Here is a nice little overview of controlling A1c through basal/bolus
As it says " If you generally have higher numbers throughout the day, you may need to increase your long-action insulin, or if your numbers are generally low, you may need to decrease your long-action insulin. "

www.diabeticconnect.com/diabetes-information-articles/general/2190-understanding-your-a1c-7-a1c-lowering-tips-for-insulin-users

Here is a nice interview with Al but not the one I am looking for
www.diabetesincontrol.com/an-exclusive-interview-with-al-mann-founder-and-ceo-mannkind-corp/

[agedhippie]

Jun 7, 2018 19:15:11 GMT -5 sayhey24 said:

Aged - while I understand why you said the following, as Al would say "its medically incorrect"

You said - "you use the same amount of basal insulin if your baseline is 100 or 300. If you are flat at 200 on basal only and want to be flat at 150 then you correct with prandial insulin to get to 150, you do not increase your basal to do that. Basal insulin is there to cover basal glucose and basal glucose is constant day to day. I know this is how it works because it was what I was taught to do"

There was a really good interview with Al on this but I can't find the link. While I look for it think about what happens in a non-diabetic. Assume 85 as your fasting baseline - what keeps you at that? The amount of insulin released by the pancreas during fasting. If you could control your pancreas and wanted to be at 80 - what would you do? Yes, have the pancreas release more insulin during fasting.

In both cases first and second release during meals will bring you back to your baseline which could be the 80 or 85. Once you start going below your baseline the alpha cell's will wake up, signal the liver and will start releasing sugar.

I understand why you were taught to control your baseline with your prandial and not your basal. Simply said both your basal and prandial were not capable of replicating natural insulin release. Your basal could not properly regulate your fasting periods. More at issue is your prandial is a mess and all over the place. You never stop the spike, you go high, then you go low and once the out of control elevator stops its anyone's guess what floor its going to stop on.

However, the medically correct approach is to have you understand what your target baseline is and control it with the basal. Then use the prandial to stop the spike and bring you back to baseline in about 2 hours. This is the way the body works.

Its also the hurdle Mike faces in trying to sell afrezza. All the diabetes experts want to put afrezza in the "Insulin Box". We have always been taught to control A1c with our prandial, right? If you have a hammer and a screwdriver but the head keeps flying off the hammer, use the handle of the screwdriver to pound the nail. Good Grief! Everyone knows insulin is dangerous. It has needles. Its a mess. Yes, afrezza has been placed in the box and Mike needs to get it out of the box.

The great new is afrezza is not insulin as we all know insulin. The BAD news is everyone knows afrezza as insulin. If they just knew it as a "Super Powder" it would be the "Next Gen" class of anti-glycemic - the GSP class (Glucose Super Powder). Afrezza has the ability to truly mimics how the body works during first and second phase release. For the T2 its really easy, just take enough afrezza to get you back to baseline in 2 hours, If you take a little too much, no problem as the liver will kick in. For the T1 on the AP just take the afrezza with a bit more care to get you to baseline and the AP will use the RAA as the basal to keep you flat. For the rest of the T1s Tresiba seems to be the winner for most.

Here is a nice little overview of controlling A1c through basal/bolus
As it says " If you generally have higher numbers throughout the day, you may need to increase your long-action insulin, or if your numbers are generally low, you may need to decrease your long-action insulin. "

www.diabeticconnect.com/diabetes-information-articles/general/2190-understanding-your-a1c-7-a1c-lowering-tips-for-insulin-users

Here is a nice interview with Al but not the one I am looking for
www.diabetesincontrol.com/an-exclusive-interview-with-al-mann-founder-and-ceo-mannkind-corp/

I see the problem. If you have a functioning pancreas then it is continually tweaking your glucose levels which is how it maintains your basal. The artificial pancreas and hybrid loop systems to the same - there needs to be a feedback loop. Basal insulin comes into play when you are not using any of those approaches. This is either delivered as prandial insulin by pump where the pump drips a constant stream of prandial insulin into you to handle the basal glucose output, or where you use a long lasting insulin to deal with that output.

You need that continual insulin stream because you cannot bolus overnight as you are asleep and the basal glucose will mean that you wake up in the 600s in DKA (or not wake up at all). Leaving pumps aside if you are on MDI or Afrezza you need something like Tresiba or Lantus to cover that basal glucose output, and only the basal output. If you don't eat for any reason you do not want the basal dragging you low which is why basal must keep you flat and not move your level up or down.

You are confusing a basal response, the body using it's insulin to return you to your baseline with the role of basal insulin which is to keep you level because it is dumb and doesn't know where the right level is, but the body does. You do not want to rely on the liver providing you with extra glucose because it only does that if you are hypo in response to glucagon. If you are dropping what the body does is first stop putting out insulin and accelerate the removal of insulin which keeps glucose circulating, and only then at around 55 to 60 does it start to release glucagon to prompt the liver to release glucose.

On a practical note you don't change basal insulin levels often because you have to leave a couple of days between changes to get a true reflection of the new dose. Also your basal output drifts but very slowly so calibrating twice a year is fine.

[sayhey24]

Aged - I am glad you see the problem. Simply put, what you were taught is medically incorrect. It is however understandable because your medical team was doing the best they could with the tools they had.

Al saw a "Next Gen" patch pump to do the constant tweeting you describe but the Tresiba users seem to be doing pretty well. For the T2s with enough beta cell function left, their pancreas will do the tweaking.

From the AP study with afrezza the future is pretty clear; pick your target baseline; keep it at that level through the AP basal; get back to baseline asap with afrezza.
www.ncbi.nlm.nih.gov/pmc/articles/PMC4604530/

What I suggest is you finally give the afrezza a try. I will guarantee your lungs will not explode as your Endo was once concerned about. Even better, after three years afrezza users are not seeing lung function decrease and a few have reported increased function. That is not only awesome but unheard of.

[agedhippie]

Jun 10, 2018 10:01:57 GMT -5 sayhey24 said:

Aged - I am glad you see the problem. Simply put, what you were taught is medically incorrect. It is however understandable because your medical team was doing the best they could with the tools they had.

Al saw a "Next Gen" patch pump to do the constant tweeting you describe but the Tresiba users seem to be doing pretty well. For the T2s with enough beta cell function left, their pancreas will do the tweaking.

From the AP study with afrezza the future is pretty clear; pick your target baseline; keep it at that level through the AP basal; get back to baseline asap with afrezza.
www.ncbi.nlm.nih.gov/pmc/articles/PMC4604530/

What I suggest is you finally give the afrezza a try. I will guarantee your lungs will not explode as your Endo was once concerned about. Even better, after three years afrezza users are not seeing lung function decrease and a few have reported increased function. That is not only awesome but unheard of.

I think the Type 1 / Type 2 mix is the problem. Lets take Tresiba - as Type 1 if I am at 200 with a target of 100 and I do not eat I will sit at 200 all day as Tresiba holds me steady. If Tresiba were to drop me to 100, my base, then The next day when I am at 150 Tresiba will drop me to 50 which is bad. Instead I take prandial insulin to get to me to my baseline, and then Tresiba holds me there (as long as I don't eat). That's how insulin works in Type 1 - basal holds you flat by neutralizing the background insulin, prandial returns you to baseline in response to carbs or events. It is a cardinal sin to use Tresiba to cover food.