My understanding of Afrezza fundamentally changed

I've been following closely news of the inhalable insulin, Afrezza, since I became aware of it a few years ago. Its purported faster action was the main feature that interested me. I understood that it peaked in 12-15 minutes but it appears that my understanding was not complete.

After doing a google search on Afrezza yesterday, I discovered that the official prescribing information is now available. On pages 15-16 under the clinical pharmacology section I found this narrative:

Absorption: The pharmacokinetic profiles for orally inhaled AFREZZA 8 units relative to subcutaneously administered insulin lispro 8 units from a study in 12 patients with type 1 diabetes are shown in Figure 3(B). The maximum serum insulin concentration was reached by 12-15 minutes after inhalation of AFREZZA 8 units and serum insulin concentrations declined to baseline by approximately 180 minutes. However, the faster absorption of insulin from Afrezza [see Figure 3(B)] did not result in a faster onset of activity compared to insulin lispro [see Figure 3(A)].

While the serum insulin concentration peaks in 12-15 minutes, this quicker absorption did not lead to faster action.

Now I'm wondering how this insulin will really help me. The main attraction to me was to pull down high BGs quickly. If I interpret the referenced published information correctly then the onset of action for Afrezza is comparable to insulin lispro (Humalog).

The Figure 3 graph does show that Afrezza leaves the system well ahead of insulin lispro. That's an important benefit.

I guess I'll just have to wait and try it myself to see if it will help me but for now I am disappointed. Again, the devil is in the details.

What I really don't understand is that the area under the curve for the GIR for Afrezza is much smaller than lispro. That would seem to say that unit for unit, Afrezza would be less potent, but they claim it isn't.

The real test will be the outcomes of the patients who use it over longer periods of time… Time will tell

I don't understand that, either. I remember one post here at TuD, an Afrezza trial user seemed unconcerned with getting the exact dose precisely figured with Afrezza. It seemed to him to be less worrisome when compared to injected insulin. Many commenters here just couldn't imagine dosing only in 4 or 8 unit increments.

I guess I won't really know the personal truth of Afrezza until I do my n=1 experiment.

You're right, Sam. I wonder what the long-term effects are on users of other inhalable meds, like those for asthma.

I have been pretty surprised at what seems like a negative reaction from the diabetic community before its even become available-- people saying there’s no way it could work for them, etc due to their insulin sensitivity (even though its been demonstrated to work, and work well on t1 patients with actualy reduced hypoglycemia in trials). Etc etc, it just seems like people want to dislike this concept for some reason. And I’m not sure why. I hope it proves to be a game changer for diabetes everywhere, and I think it has the potential to be

Well, for me it would work much faster than lispro . . . since lispro doesn't work for me at all. LOL.

But this is indeed interesting. As with you, the faster action was what captured my attention. But like many others, I also have question marks about the dosing. Eight units is a HUGE bolus for me. So I still need to wait and see what sizes they decide to package it in.

David - It appears from the prescribing info that it will be packaged in 4 and 8 unit cartridges. I suspect that due to the respiratory delivery route, the effect of the dose is not exactly comparable to injected insulin.

I remember the responses to the Afrezza trials user's post here. Overall, they were very skeptical. I think the poster finally gave up and I haven't read anything here by him since.

I am biased toward hopeful developments in diabetes treatments. The danger for me is getting my hopes ahead of reality. A healthy skepticism is always good but sometimes people overdo it. They feel more comfortable being skeptical yet wrong rather than being naive or gullible.

What surprised me now is the distinction that insulin serum levels are different than onset of action. They each occur at two different times.

"Now I'm wondering how this insulin will really help me. "

Hi, did you get your answer? Looks like there is a discussion now going on started by MikeP.

How could faster insulin absorption not lead to faster onset of activity? Afrezza ends up in the blood more quickly, but it doesn't interact with other cells more quickly? That seems bizarre, I wonder if we're misinterpreting that language.

The actual experience by the early adopters of Afrezza seem more significant to me than the clinical pharmacology narrative that I cited above. Every profession has their own language and jargon and I might not be interpreting their words as they intended them to be decoded.

Yes, I've been following Mikep's discussion closely. I will start on Afrezza this Thursday, March 12. Then I will have first-hand experience to report.

Niccolo - I'm still puzzled by the statement "faster insulin absorption did not lead to faster onset of activity." It could be sloppy technical writing or just that the words mean something different to professional like a pharmacist.

On March 12 my direct experience with Afrezza will give me a new perspective.