Inhaled Insuiln - Afrezza

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Afrezza became available in pharmacies on January 26, 2015. It is a brand new inhaled insulin. It is made out of molecules of regular human insulin that have been encapsulated in a special coating. Readers who have followed my blog know that I was very negative on the first inhaled insulin, Exubera. That was because it was extremely hard to dose and did not appear to be as good as injected insulin.

I have been following the Afrezza story for almost two years now, and am cautiously hopeful that, unlike Exubera, Afrezza will be a much more useful product for some people, though my initial enthusiasm has waned now that the drug has been released and we know more about its pricing and efficiency.

What makes Afrezza interesting isn't just that it's inhaled rather than injected. That's a nice feature that will appeal to the many people with Type 2 who really need insulin but won't start it out of misguided fear of needles. Insulin needles are painless when prescribed correctly, and many people with Type 2 can get decent control using injected meal time insulin--possibly much better control than is available with Afrezza. So needles alone is not a good reason to avoid insulin.

So while Afrezza may be good for needlephobes, what really excited me about Afrezza was its activity curve. It is different from all the existing injected insulins and does something that no other drug does. To understand what that is, you need to understand how our bodies normally produce insulin, in two distinct phases. You can read more about this HERE. All the current injected insulins replace second phase insulin production. They take about an hour to start working and several more to exit the body. But Afrezza appears to replace first phase insulin production which just happens to be the part of insulin production that disappears first. People diagnosed with Type 2 diabetes have usually lost all their first phase insulin production while retaining a lot of their second phase capability.

When first phase insulin fails the liver will continue to dump glucose into the blood stream even after a person has started to eat foods that will raise their blood sugar. This makes the post-meal blood sugar spike higher. By restoring first phase insulin with Afrezza, it is possible to lower the post-meal spike and thus lower how much supplemental insulin is needed.

This means it might be an excellent drug for people recently diagnosed and one that is much safer than the drugs like Januvia or Victoza many are being put into at that time, whose dangers I have discussed elsewhere.

One major problem with injected insulin is that it takes a long time to exit the body. This means that you can still have insulin working a couple hours after you have finished digesting your meal. This can cause hypos and makes doctors dose fast-acting insulin very conservatively. They don't give you enough to really cover your meal because of the fear that the lingering insulin will cause lows. But because Afrezza leaves the body much more quickly, you may be able to take a larger dose that will lower your blood sugar post-meal much better, knowing it will be gone right after it lowered your blood sugar.

The above is based on the claim made by the drug company that makes Afrezza and it is supported by activity curve graph published in the prescribing information which you can see in the graph to the right:


Lispro, which is what Afrezza is being compared to here, is Humalog.

How It Works

Afrezza comes in cartridges that you put into the small inhaler, inhale, and throw away. The inhaler does not need to be cleaned. Every two weeks you throw out the inhaler and use the second one that comes with the cartridges.

The doses come in cartridges sold in increments of 4 units. Because of the fast way Afrezza operates, it may be possible to use a significantly larger dose than you would use if you were injecting a slower fast-acting insulin. Also, because the insulin comes in the form of an inhaled powder, it is possible that not all the insulin gets to the lungs and then into the blood. The prescribing information for Afrezza makes it sound like 4 units would be appropriate for anyone using up to 4 units of injected insulin. But reports posted online from a few people who have tried Afrezza suggest that dosing properly is complicated and requires a lot of experimentation to get right. It can take twice as many units of Afrezza to cover the same amount of carbohydrate as the same dose of injected insulin. At the same time, people whose main problem is a lack of first phase insulin may get along well with small doses.

Even After Almost Two Years There Are Few Reliable Reports from the Wider Diabetic Community About How Well Afrezza Actually Works

Immediately after Afrezza hit the market, reports posted on diabetes social media sites were encouraging, with several people with Type 1 diabetes posting CGMS graphs showing flat blood sugars. However, over the next months only these same few people continued to post aggressively on social media. Of the few who joined them, many were investors in the company that makes Afrezza. This raises the question of whether this is an "astroturf" web marketing campaign, rather than a real reflection of user experience. Discussions on investor discussion boards devoted to the stock of the company that makes this drug are full of investors plotting strategies to promote the drug, which have included posting fake reviews, visiting forums, and the like.

To make it even more difficult to evaluate the actual performance of Afrezza in people with many different kinds of diabetes, people who have posted negative experiences with this drug have several times been bullied online by investors and by the dominant very early adopters, some of whom are also investors, who post frequently on Twitter. This discourages open dialog.

There has been very little discussion of Afrezza on diabetes discussion boards, and when it occurs, it is often from people who have not been otherwise active posting on these discussion boards.

During the course of 2016 a couple of high profile Type 1 bloggers have adopted Afrezza and reported on it with enthusiasm, which is encouraging, but publicly available information about how many prescriptions are currently being dispenses for Afrezza suggest that very few people are actually using it and that many people who tried it have stopped using it. This may be because of the difficulty of getting insurance coverage, since Afrezza is very expensive without good coverage,

Who Appears to Benefit Most from Afrezza?

Most of those reporting their results on Twitter (the only place where there is much discussion of Afrezza) are people with Type 1 Diabetes who had been having a great deal of difficulty controlling their blood sugar using the tools that many other Type 1s have been more successful with, like pumps and CGMS. Several of these have reported dramatic decreases in A1c. They also report being able to tolerate a higher dose than the corresponding amount of injected insulin they usually use. This suggests strongly that a unit of Afrezza is about as effective a half a unit or less of injected insulin I have seen no reports from people with Type 2 who have the kinds of blood sugar levels that would motivate most physicians to prescribe insulin--i.e. blood sugars ranging from 300 mg/dl to 400, mg/dl after meals. The very few Type 2s posting about Afrezza, some of whom are also investors, appear to much milder forms of Type 2, some of which verge on Prediabetes. Afrezza works well for them, as we would expect it to, since the dominant feature of early Type 2 (and prediabetes) is the loss of phase one insulin release that occurs in normal people right after eating and the persistence of the later, slower phase two insulin response.

However, since the target person with Type 2 who is most likely to be prescribed insulin rather than one of the newer, expensive and highly risky orals, is a person who no longer has any second phase insulin response left, it is questionable how well they will respond to Afrezza. Because Afrezza will only cover the high glucose that results during the first hour after eating. The persistent glucose "long tail" these Type 2s experience after eating will not be covered by a single dose of short-acting Afrezza. They will probably need a second, correction dose, taken another hour or so after eating. This probably explains why the FDA approved Prescribing Information for Afrezza only discloses the results of a study in people with Type 2 where Afrezza was compared against the use of no other insulin, just oral drugs. My guess is that Afrezza does not compare well in people with advanced Type 2 diabetes when pitted against a basal/bolus regimen with fast acting insulin injected at meals, or for that matter against 70/30 mixes, as I believe it was matched against that kind of insulin in trials run as part of the drug approval process, which are not cited in the Prescribing Information.

The Downside of Afrezza: Pricing and Packaging

As mentioned earlier, most of the Type 1s who are using Afrezza successfully are using it not only at meals but taking one or more correction doses after meals and at other times of day when their blood sugar starts to rise. But Afrezza is much more expensive than the same number of units of injected insulin, and the way that Afrezza is dispensed, in 90 dose packages, which allow only for 3 doses a day, means that a person may need two or three boxes to cover a month's worth of dosing. Very few insurers will cover this much insulin.

Another problem with the packaging is that Type 2s put on insulin are not given much diabetes education, unlike people with Type 1, and few are taught to administer correction doses. Instead, most are just told to use a set amount at meal time and may have trouble figuring out how much to use for a correction. They may also have trouble, given the way the drug is currently packaged getting enough insulin to cover three meals a day, since the packages containing the largest doses available, the 12 unit dose, also include smaller dose cartridges. This makes it necessary to order several boxes to provide even three 12 unit doses a day for one patient. And of course, the typical Type 2 who needs meal time insulin is more likely to be using 20-30 units at a single meal than 12, which becomes even more problematic when you remember that 12 units of Afrezza may be the equivalent of much less injected insulin. So the expense of prescribing Afrezza in truly effective doses to people with Type 2 diabetes is such that we aren't likely to see many insurance plans approve this drug any time soon unless the company making and marketing Afrezza drops the price dramatically and rethinks the way it is currently packaged. They currently have no plans to do this. For now, the difficulty of providing large enough doses to cover meals for people with insulin resistant advanced Type 2 diabetes, combined with the apparent need to use, and understand, correction doses, may keep this from being widely prescribed to the people with Type 2 who need insulin but fear needles.

Afrezza is Best for People with Type 1 and Very Recently Diagnosed, Mild Type 2

The success stories we are hearing about Afrezza are from people with Type 1 diabetes, for whom the size of the doses supplied in today's packaging options are appropriate.The little bit I've been able to garner from what I've read and heard from people with Type 2 using Afrezza suggests that it is also working for people who are not extremely insulin resistant, whose whose blood sugars are extending perhaps into the mid 200 mg/dl range after eating high carb meals, and who have extremely good insurance and the ability to convince a doctor to prescribe this drug to them.If you fall into that category, it would be worth a try.

Afrezza Can Cause Hypos

One of the things that the investor community keeps insisting on is that Afrezza can't cause hypos. It does not appear to cause dangerous hypos in people with Type 1 diabetes who know what they are doing. However, I have personally received hypo reports, and there were quite a few reports of severe hypos in the studies used to approve the drug.

Like any insulin, Afrezza can cause serious hypos if Afrezza is taken at the wrong time, so that the insulin in the blood doesn't meet up with the carbs released by a recent meal. Hypos are possible too if too much is taken. Hypos are more likely, too, for Type 2s who need to use very high doses of insulin because of insulin resistance. This risk is moderated only by the fact that most people with severe Type 2 don't get prescribed prescribed enough Afrezza (or any other insulin) to fully cover their high carb meals, since doctors know that they aren't taught how to use insulin correctly. This means they will avoid hypos only because continue to experience dangerously high blood sugars.

Limitations of Use of Afrezza

Because it is inhaled, Afrezza can not be taken by people who have lung problems or by smokers. Because the long-term impact of exposing lung tissue to a growth-promoting hormone--insulin-- is unknown, the FDA insisted on much longer, more rigorous testing for Afrezza. I had originally thought that the testing for Afrezza had gone on longer than that for Exubera, which did eventually appear to cause some excess lung cancer, but that does not appear to be true, so a certain amount of caution would be advisable.

I would personally be willing to give it a try, if I didn't live in a region where not a single insurance plan available to me covers Afrezza, but I would not use it for every meal. If you do experience prolonged bouts of coughing after using Afrezza that don't go away after a week it's probably a good idea to avoid it.

If your doctor does prescribe Afrezza, be sure that he or she follows the instructions on the Prescribing Information and sends you for a lung function test before you start Afrezza and then follows up with one six months later. Also make sure that you doctor starts you on the "titration pack" currently being offered, which gives you enough Afrezza to let you experiment a bit and figure out the proper dose that will work for you.

If you are having trouble getting coverage for Afrezza, a program called MannKind Cares offers support to doctors in filling out prior authorization forms that may be required by insurers. If you need help in figuring out how to dose it, there are people with experience using it posting on on Twitter (hashtag #afrezza) and Tudiabetes.com who may be able to help you out.

Please Report on Your Own Afrezza Experience to Help Others

If you do try Afrezza, please let me know how it works for you. I will use credible information to improve the information I offer here as I do with all the drugs I cover.

The more detailed your reply, the more useful it will be to others. In particular, please let me know what your blood sugar would have been for a meal you controlled well with Afrezza had you eaten it without insulin, what amount of fast acting injected insulin you would have used to cover that same meal, and how much Afrezza you used to cover that ame meal. Please make it clear if you have Type 1 Diabetes diagnosed in childhood, LADA (Type 1 Diabetes diagnosed in adulthood) or Type 2 Diabetes. Use the email link found on the CONTACT tab at the top of this page and title your email "Afrezza report."

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