It's because when you start to go low your pancreas and liver counter-regulate with glucagon, and in the case of Afrezza it doesn't hang around long enough to really frustrate that mechanism.
Ah, that is an important nuance. If you take too much injectable insulin, and it starts to push you low after a few hours, the long tail of insulin action will prevent the release of glucagon that would facilitate some self-correction. If you take too much Afrezza, by the time it starts to push you low, it's largely out of your system, so your body can do its thing and counter-regulate with glucagon and raise your BGs back up, or at least keep them from dropping so far.
I actually don't know enough about glucagon to be able to predict how this would play out, i.e. how much Afrezza dosing error could be compensated for via glucagon. I'd love to be educated on glucagon-related issues, any sources you've found useful? Or care to just drop some knowledge here yourself?
This forum is a really fantastic information source.
Its bizarre-o! Go Go guinea pig, Terry! I don't want to experiment with this one, but I am interested in what happens when you do.
Yep, that makes sense. Still curious to understand glucagon dynamics better down the road. Really appreciate your insight, my doctors give me a hard time for being reasonably versed in the literature, but you're the next level! And yes, coming from me, that's a compliment...
Why, on earth, wouldn't they include a 2u dose?
Because they studied the subject ad nauseum as did the FDA and it was determined that the dosing provided for was the most appropriate for both type 1 and type 2 diabetics. Again it is not the same thing as injected insulin and can not be compared to injected doses. The body metabolizes things differently through different mechanisms.-- a pot smoker gets a different high from smoking it than eating it. It is not comparable.
I suspect they had to start with a limited number of doses, and 4 and 8 were the two that made the most sense for meals for people on the normal moderate or high-carb diets. In theory, it would seem to make more sense to do 1 and 2 units doses, and let people take multiple, but I think there's a cost associated with each dose, so this could get pricey. I believe a 2 unit dose is planned, however.
Dave has some very good explanations for why dosing is a bit less critical due to the lack of an insulin action tail suppressing endogenous glucagon.
But that's not at all the same thing as dosing not mattering. And no one who has suggested dosing might not matter much has suggested a mechanism whereby this might work, e.g. something about the medication, or the lungs, or some other factor, that would somehow mediate insulin availability based on the amount of glucose present.
Maybe dosing really won't matter, because there's some mechanism at work we don't understand and have trouble even postulating. I don't see anything in the information we do have access to that suggests that, but crazier things have happened, and mostly at this point we'll just have to see, we should know more soon enough.
Keep in mind a lot of folks get put on either fixed doses (like our new community member Madison) or a sliding scale, rather than carb-counting and matching doses to food. So cruder dosing increments are perfectly consistent with a lot of current medical practice even aside from the question of how carefully Afrezza needs to be matched to carbs.
Gottcha
I'm looking forward to seeing how all of you make out with this if you try it. I have mild asthma and I'm still concerned about the lung issues so I most likely won't even try it. I won't say never though, since I'm on a pump now too and didn't think that was going to happen. If this works maybe it could be used to bring down a spike. I'm also concerned about something that works so rapidly for eating because I sometimes crash if I bolus before eating.
The dosing is interesting and that they didn't see as many hypos as injected/infused insulin. I remember reading someone here said that she thought the insulin may stay in the lungs, I wonder about all of this. I use ventolin for asthma when needed and I used imitrex in a nasal spray- the imitrex spray caused a mild allergic reaction in me with some facial swelling so I only use the pill form now where I can control the dose and my nasal passages aren't exposed that way.
So, this is the first fast acting one to hit the market? I thought it might be faster. Seems to knock an hour off the tail, which is nice, but not the 2 hour window I'd hoped it might confine itself to. The breadth of my medical knowledge is limited and I don't quite know how to phrase this question, I'm just up late with low blood sugar...apologies. Is it faster because it becomes inert after 3 hrs? Or is it physically/actively doing something different than insulin? Does that question make sense?
Dave, you got me all excited about these rapid actors, early on in my effort to problem solve my BG issue. I'm still excited, but a little wary. Hit the market faster than I imagined it would. Its ready for me before I am ready for it. That's a** backwards. I'm kinda on board for the black magic in the dosing. I, honestly, have no idea how much correction I should be delivering during intense, sustained exercise, anyway. I'm always just guessing.
The lungs are a pretty direct pathway to the blood. The Afrezza powder turns to liquid insulin in the lungs and then gets absorbed from there into the bloodstream. So it starts fast, peaks fast, and finishes fast.
Contrast that with a subcutaneous injection. Insulin gradually diffuses from the subcutaneous tissue into the surrounding blood vessels, so it starts slow, peaks slow, and finishes slowly, too (slow being relative, of course, but the point is that there's a mechanical limitation to how fast subcutaneously injected insulin can work, whatever chemical tricks one plays with the insulin itself).
Given the mechanism, Afrezza has less of a tail to suppress glucagon response, so the body has a better chance of correcting hypos from an excessively large Afrezza dose relative to the meal consumed (kudos to Dave for pointing this out). That's very different from saying the dose doesn't matter. But I've become a total broken record on that. :(
For less rapid-acting carbs, higher-fat meals, and especially circumstances where people are currently taking (or would like to take) extended boluses with their pumps, the speed of Afrezza will actually be a liability, because it'll be gone while the meal is still raising BGs. But for fast-acting carbs, it'll match far better than current injectables. So basically, Afrezza appears ill-suited to anyone pursuing a low-carb diet, both because of the large minimum dose and because of the speed with which it ceases to lower BGs.
That, anyway, is my best assessment. We'll know more soon enough!
I'm keeping my eye on this. As a general rule I won't try a drug until it has been on the market for a year or so and my insurance accepts it as a preferred drug. Even though Afrezza was required to go through additional trials to establish safety wrt lung damage, the FDA approval still noted that it has concerns over long-term lung damage. And at least right now the pricing is pretty high, the street price for Afrezza for 12 units is $12/day about twice what a modern analog rapid insulin costs.
And I also have concerns about the dosing since I take 5-10 units per meal, only having a choice of 4 or 8 unit single doses seems crude. And I have heard about reduced hypos. I am keeping an open mind. It may well be possible that our bodies can regulate insulin levels with Afrezza. Our livers actually clear insulin and the liver responds to higher insulin pulses with increased insulin clearance. So it may actually be that one of our body's normal regulating mechanism works with Afrezza whereas it doesn't work with more slowly released injected insulins. I'll keep an open mind.
Thanks guys.
So, the liver is contributing by punching back any excess insulin. That's kinda what I was wondering. The body pulls some sugar out of hiding to cancel out the excess insulin. This works faster by not disabling innate mechanisms. I like that.
To me, Afrezza seems more like a tool that I'll possibly add to my toolbelt, rather than replacing my insulin pump entirely. The 3 use cases that I see myself possibly using Afrezza are:
1. When my BS is very high (>200) and I don't already have a lot of IOB
2. When my BS is normal and I'm eating high glycemic carbs
3. When I'm not able to wait between giving myself an insulin dose and eating
I think I'd use my pump for all other scenarios, and so, just taking a wild guess, I think about 80% of my total insulin use would still be from my pump.
That said, one thing that's really unfortunate is that there's no way to manually add a non-pump insulin dose to my pump, so that it could keep track of the IOB from my Afrezza dose, or even on those rare occasions when I use an insulin pen. I'm using a Ping and switching to the Vibe this week. Do any other pumps allow for that? Are there any other solutions any of you could think of?
Would love to hear your thoughts.
I think its so hard to find exactly what you want. You might have to write your own user interface for data collection for your phone. There are no rapid acting liquid insulins in development, are there? Do IM injections get on board faster than the inhaled, or slower?
<blush> thanks, man!
What you wrote is what I am thinking. The Afrezza has way to many limitations IMO:
One is the need for long acting insulin has not been eliminated. So I would still need my pump and all of it's products for the basal. I don't want to add something else to carry around in my bag.
Two is the dosage. 4 units is more than I need for a meal and certainly for any type of correction. So in addition to needing some bssal insulin, we would need some rapid to fix a high bg.
Three is the incidence of cough that was experienced by 27% of the trial. Not Good. Anyone with lung / cough / breathing issues / or smoking history BEWARE.
I am keeping my eyes and ears open on this stuff. I love progress but this seems like the the opposite of progress. One fun thing could be that for folks who love to tell folks "excuse me, I need to shoot up", they could now say "excuse me, I need to take a snort".