Afrezza Lack of Awareness & Afrezza Learning Curve

[sportsrancho]

I’ll be back ..I just now read all this, my girlfriend had to evacuate from her home in Oldsmar and now is in a shelter in Orlando Florida.

This does all tie in with the people that have left that thought they could make a big difference and couldn’t. The lack of awareness and the Afrezza learning curve is the most important topic to date IMO.

[buyitonsale]

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.pdf

[stevil]

Sept 29, 2022 0:15:52 GMT -5 buyitonsale said:

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.pdf

Now 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.

[mango]

FDA approval of Afrezza Pediatrics has Standards of Care changing potential considering the Secondary Endpoint is Superiority.

I believe Afrezza Peds will drive the paradigm shift and will ultimately lead Afrezza into becoming the blockbuster success it was always intended to be.

Afrezza will ultimately receive the recognition it deserves and rightful place as the Gold Standard of mealtime insulin within the Standards of Care.

Secondary Outcome Measures :
Change in HbA1c [ Time Frame: 26 weeks ]
Change in HbA1c from baseline to Week 26, for superiority assessment

Change in Fasting Plasma Glucose (FPG) [ Time Frame: 26 weeks ]
Change in FPG from baseline to Week 26, for superiority assessment

Event rate of pooled level 2 and level 3 hypoglycemia [ Time Frame: 26 weeks ]
Event rate of pooled level 2 and level 3 hypoglycemia (self-monitored blood glucose [SMBG] <54 mg/dL and/or severe hypoglycemic events) during the 26-week randomized treatment period, for superiority assessment

[cretin11]

Appreciate your thoughts, stevil. The cognitive dissonance on this board is strong, we've all experienced it at one time or another (many still do). You have a valuable perspective from your training and your posts provide a service to us.

[agedhippie]

Sept 29, 2022 0:15:52 GMT -5 buyitonsale said:

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.pdf

The low carb diet works to a point. Before insulin was available it was the standard treatment and a Type 1 could survive up to 4 years on it, a Type 2 could survive longer although progression got them in the end at around the 10 year mark. These days I expect a Type 2 could get a far longer run because of drugs, better treatment of complications, and more understanding of nutrition.

The problem with LCHF as an approach is that mostly people cannot not stick with it in the long term. This isn't a reflection on the LCHF diet itself, just a reflection of the fact that lifestyle changes are notoriously hard to maintain. The paper you cited shows what I would expect; Type 2 is a relative rather than absolute insulin deficiency so if you can reduce your weight you reduce your insulin resistance and you no longer have a deficiency - you are below the red line. The problem is that the red line declines over time (progression) and you will hit it again eventually. This is what used to kill pre-insulin era Type 2 diabetics, your weight can only go so low before you die.

[agedhippie]

Sept 29, 2022 11:44:16 GMT -5 mango said:

FDA approval of Afrezza Pediatrics has Standards of Care changing potential considering the Secondary Endpoint is Superiority.

I believe Afrezza Peds will drive the paradigm shift and will ultimately lead Afrezza into becoming the blockbuster success it was always intended to be.

Afrezza will ultimately receive the recognition it deserves and rightful place as the Gold Standard of mealtime insulin within the Standards of Care.
...

The issues here are that it's pediatrics, not adults, and that it is not a long term study so there is no way to know what the long term benefits actually are as opposed to expected to be. That is why it will not change the SoC. However, it will make the use of Afrezza more acceptable as a mealtime insulin within the Standards of Care as an alternative to MDI.

The trial does not address Afrezza vs. AID pumps which is where the pediatrics endos are currently focusing.

[mango]

Sept 29, 2022 12:01:21 GMT -5 agedhippie said:

Sept 29, 2022 11:44:16 GMT -5 mango said:

FDA approval of Afrezza Pediatrics has Standards of Care changing potential considering the Secondary Endpoint is Superiority.

I believe Afrezza Peds will drive the paradigm shift and will ultimately lead Afrezza into becoming the blockbuster success it was always intended to be.

Afrezza will ultimately receive the recognition it deserves and rightful place as the Gold Standard of mealtime insulin within the Standards of Care.
...

The issues here are that it's pediatrics, not adults, and that it is not a long term study so there is no way to know what the long term benefits actually are as opposed to expected to be. That is why it will not change the SoC. However, it will make the use of Afrezza more acceptable as a mealtime insulin within the Standards of Care as an alternative to MDI.

The trial does not address Afrezza vs. AID pumps which is where the pediatrics endos are currently focusing.

The trial is 26 weeks.

The results from the ABC trial will disrupt the pump thinking when it shows Afrezza plus basal can get the same results or better.

[sayhey24]

Sept 29, 2022 10:50:52 GMT -5 stevil said:

Sept 29, 2022 0:15:52 GMT -5 buyitonsale said:

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.pdf

Now 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.

Yes is the answer.  If you can achieve with a low carb diet they same results as afrezza then either will work.  Richard Bernstein is the example here.  What he does is eliminate the post meal spike and keeps his BG in a non-diabetic range.  Granted, Bernstein was not a doctor when he started doing this and only became one because he was living the Dunning-Kruger effect or so said the medical community.  The problem with Bernstein's approach is keeping true to his diet is really hard and I know I could not do it.  The bottom line is afrezza obsoletes the need for Bernstein's diet.  The goal is to stop the spike and get the PWD under 140 in <2hrs.

Hyperinsulinemia and insulin resistance is an interesting discussion.  What causes it?  What we do know if we autopsy the T2 pancreas we find destroyed beta cells, reduced beta cell mass and some normal looking beta clusters.  We also know with Covid we have seen a big up-tick in beta cell destruction and reduction and a boat load of new T2s.

Why is it that if the body is making "good" insulin the body is not using?  We know that if we give the T2 enough extraneous insulin their body will properly use it and we know if at meal time we give the insulin early and stop the spike we need to give the PWD a lot less insulin.  Why is that?  We also know that after the BG rises and the pancreas has been pumping out its insulin and doing whatever its doing, we need a lot more extraneous insulin.  Why is the extraneous insulin properly used but the body's insulin is not?  Could it be something is wrong with some of the insulin the body is releasing?

That was the discussion Al Mann had with Ralph DeFranzo years ago.  Ralph's position was the body already had enough insulin which may be true.  Al position was the body did not have enough insulin which could be used by the body.  Now Ralph is a doctor and Al was not.  What would happen if afrezza was used to stop the spike and get the T2 back to a non-diabetic fasting state quickly.  Would the body continue to dump its insulin causing the hyperinsulinemia situation you are concerned about?  We also have to remember Ralph was starting to hawk GLP1s at the time and he was pushing the idea that the T2 is already making enough insulin.

[mango]

I believe Pediatric approval will also drive demand solely based on the fact kids and young teens hate needles and do not like pumps attached to their bodies. There’s also a lot of drawbacks and limitations with pumps and you can get the same or better results with Afrezza plus a once a day basal injection, which we will see confirmed via ABC trial later but has also been confirmed by real life Afrezza Users for years.

A few details concerning Pediatrics and Pumps:

• Over the past 14 years, 1774 (7%) of all insulin pump adverse event reports were identified in children ages 1–12. Of these reports, 777 (43%) resulted in hospitalization. In hospitalized cases (n = 614), diabetic ketoacidosis and/or hyperglycemia were the predominant patient problems, and in other cases (n = 98), hypoglycemia was evident. There were 106 emergency room visits, 19 cases requiring paramedic attention, and five deaths. The majority of reports indicated that the devices were not returned to the manufacturer, and root causes were not always confirmed.

• In approximately 43% of hospitalized cases, where devices were evaluated and tested by the manufacturer, the device was found to operate according to specifications. However, some pumps were found to be defective due to missing or damaged components, and a replacement device was sent to the patient. In many of the reports, the narratives revealed that pump instructions were not followed.

• A common problem was failure to prime the pump, and in several reports, the priming was done incorrectly with the tubing still attached to the child. In summary, this article underscores that many adverse events were due to use error and point to the importance of education and training.

• Hypoglycemia is a major concern in the treatment of diabetes mellitus, especially in children.4 In a recent systematic review of continuous subcutaneous insulin infusion versus multiple daily injections, Fatourechi and colleagues5 found that children had a higher risk of mild hypoglycemia when treated with pump therapy.

www.ncbi.nlm.nih.gov/pmc/articles/PMC3570839/



• Of 143 patients using CSII, 90% had previous and 63% reported current dermatological complications. Non-specific eczema was most frequently reported and was currently present in 25.7% of the patients. These results were independent of age and current CGM use. Among the 76 patients using CGM, 46% reported current dermatological complications. A history of atopy was associated with dermatological complications in individuals using CSII, but not CGM. The patients rated CGM-related dermal issues as significantly worse than those associated with CSII (P < .05).

pubmed.ncbi.nlm.nih.gov/29484783/

[sportsrancho]

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

[sayhey24]

Sept 29, 2022 13:51:33 GMT -5 sportsrancho said:

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?

[mango]

Sept 29, 2022 13:51:33 GMT -5 sportsrancho said:

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

I agree with the VDex locations. I don’t think seizing the sales force would be wise with Peds approval on deck. If we hit even just one of the three superiority endpoints that would be huge. Also, even landing a great primary endpoint is success. We need boots on the ground when we get Peds approval for those reasons, IMO.

Agree with more clinical studies. Large studies focusing on Afrezza characteristics that can change the SoC.

[buyitonsale]

Sept 29, 2022 10:50:52 GMT -5 stevil said:

Sept 29, 2022 0:15:52 GMT -5 buyitonsale said:

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.pdf

Now 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.

In my previous post in this thread I shared my opinion that Afrezza will not help T2D patients unless they are willing to make changes in their diet and eliminate the root cause for their condition. That has not changed. 
 
The reason I posted regarding the root cause for hyperinsulinemia is to point out that Afrezza or any other insulin is NOT the cause. The condition exists way before the patient is diagnosed with hyperinsulinemia and the root cause for that is improper human diet, in vast majority of cases.  Most doctors never test for Fasting Insulin or Insulin Resistance, even if the patient already showing symptoms for Metabolic Syndrome. I think they should check for that first, and if they did, then they would need to explain to the patient the root cause and hopefully prevent a future diabetic. 

Afrezza is a treatment for high blood glucose, not for diabetes.

Proper human diet is the only treatment for diabetes. In the case of T2D patients it is proven by the study I posted. It is also obvious that T2D outcomes keep getting worse despite the countless advances in drug therapies. 

 

[agedhippie]

Sept 29, 2022 13:15:01 GMT -5 mango said:

I believe Pediatric approval will also drive demand solely based on the fact kids and young teens hate needles and do not like pumps attached to their bodies. There’s also a lot of drawbacks and limitations with pumps and you can get the same or better results with Afrezza plus a once a day basal injection, which we will see confirmed via ABC trial later but has also been confirmed by real life Afrezza Users for years.

A few details concerning Pediatrics and Pumps:

• Over the past 14 years, 1774 (7%) of all insulin pump adverse event reports were identified in children ages 1–12. Of these reports, 777 (43%) resulted in hospitalization. In hospitalized cases (n = 614), diabetic ketoacidosis and/or hyperglycemia were the predominant patient problems, and in other cases (n = 98), hypoglycemia was evident. There were 106 emergency room visits, 19 cases requiring paramedic attention, and five deaths. The majority of reports indicated that the devices were not returned to the manufacturer, and root causes were not always confirmed.

• In approximately 43% of hospitalized cases, where devices were evaluated and tested by the manufacturer, the device was found to operate according to specifications. However, some pumps were found to be defective due to missing or damaged components, and a replacement device was sent to the patient. In many of the reports, the narratives revealed that pump instructions were not followed.

• A common problem was failure to prime the pump, and in several reports, the priming was done incorrectly with the tubing still attached to the child. In summary, this article underscores that many adverse events were due to use error and point to the importance of education and training.

• Hypoglycemia is a major concern in the treatment of diabetes mellitus, especially in children.4 In a recent systematic review of continuous subcutaneous insulin infusion versus multiple daily injections, Fatourechi and colleagues5 found that children had a higher risk of mild hypoglycemia when treated with pump therapy.

www.ncbi.nlm.nih.gov/pmc/articles/PMC3570839/



• Of 143 patients using CSII, 90% had previous and 63% reported current dermatological complications. Non-specific eczema was most frequently reported and was currently present in 25.7% of the patients. These results were independent of age and current CGM use. Among the 76 patients using CGM, 46% reported current dermatological complications. A history of atopy was associated with dermatological complications in individuals using CSII, but not CGM. The patients rated CGM-related dermal issues as significantly worse than those associated with CSII (P < .05).

pubmed.ncbi.nlm.nih.gov/29484783/

The issue I see with the ABC trial is that there are 8 people in each arm of the trial. That's not enough to change any minds. What it will do is show if it is worth doing a rerun with larger numbers (and more cost) to get data that will potentially move things. The control arm will be the canary in this trial because that value is already known (76.2% TIR), the trial control arm must be about there.

The theme running through this post is that it's not that pumps are dangerous, it's more that people don't always follow instructions. This is why the AID pumps are considered so important, they take people out of the loop. More to the point, by using AID pumps you can eliminate those mild hypos because the pump and CGM combine to control that range. Likewise the DKA cases get caught by the system as the climb starts and before it becomes a problem. The use of CGMs has removed a lot issues you would have seen a few years ago.

There are still issues with tubing such as occlusions, but again the pump will now tell you when they happen. It's one of the reasons that Omnipods are popular for kids because it gets rid of the tubing.

I am not sure what the exact dermatological complications are, but if it's what I think this is usually related to the adhesive. You can fix this by apply liquid skin to the area before apply the CGM or pump site. At one point Dexcom had a real problem with this, but they since changed the formula.

The selling point with small kids is that you can slap a pump and CGM on them and everything takes care of itself - you don't need to worry about them forgetting to take their insulin. You can also remotely control things if necessary (I am not sure that's really a bonus...