Wary of, interested in, or using Afrezza? You should read this

Great points, Jenny. When Banting & the boys were finally able to manufacture insulin in a semi-reliable form, it was literally use it or die for the diabetics lining up for injections. Not so with Afrezza, which makes me think I'll probably wait quite a while before trying it.

just for your info (not that we care here at tu but maybe in the real word :)) the word you want is 'err' (as in make an error) not 'air'

Yeah, I think lung cancer is probably the biggest concern.
Here is some information I could find. Source is from a well known scientic resource (it's something we physicians use for recent scientific updates). I didn't have time to look into it further but here's their take on it below. So for Afrezza based there was 2 cases of lung cancer (versus 0 in the control group) but it sounded like it wasn't statistically significant. I don't know how long they followed the patients though, because I'm sure if there is increased risk, it will be cumulative the longer you are on it. I hope that's not the case. I personally really want this succeed, because it would be great. Anyway the information is below.

Pulmonary safety — A major concern with inhaled insulin is the potential for pulmonary toxicity because of the immunogenic and growth-promoting properties of insulin [51]. It is important to note that all clinical trials included participants with no recent history of smoking (at least six months) or underlying pulmonary disease, such as asthma, interstitial lung disease, or chronic obstructive pulmonary disease (COPD). All participants had a normal chest radiograph and pulmonary function tests (PFTs) at baseline.

Combining data from all trials with Exubera, approximately 2 percent of patients on inhaled insulin discontinued treatment due to respiratory events versus 0 and 0.1 percent in the comparator groups, subcutaneous insulin or oral hypoglycemic agents, respectively. In a 52-week trial comparing Afrezza plus insulin glargine to subcutaneous biphasic insulin, a greater proportion of patients in the inhaled insulin group discontinued therapy because of adverse events (9 versus 4 percent with subcutaneous insulin) [7], with cough being the most common event leading to discontinuation.

Lung cancer — In long-term surveillance of the pre-marketing clinical trials, 6 of 4740 Exubera-treated patients and 1 of 4292 comparator-treated patients developed lung cancer [57]. There has also been one post-marketing report of a primary lung malignancy in a patient treated with Exubera. All of the patients diagnosed with lung cancer had a prior history of cigarette smoking and there are too few cases to determine if these cancers are related to Exubera. Lung cancer incidence reported with Afrezza thus far is too low (only 2 in 2750 participant-years on inhaled insulin versus 0 in 2169 participant-years in controls) to draw any meaningful conclusions [29].

Good find!

...and, IIRC, one of those two cancers was a previous smoker that should have been screen out as a member of the cohort.

Research continues... :-)

Shadow,

I come at this with my experience with Januvia in mind, too.

When Januvia was brand new I started taking it. I'd been controlling with a very strict LC diet--too strict and difficult to stick with as I was still getting spikes well over 140 mg/dl eating only 15 g of carbs. I'd switched to insulin and that was doing a lot better for me, but my doctor suggested that I try Januvia, so I did.

Januvia gave me completely normal blood sugars! Yippee! After a few weeks I stopped testing. My sugars were perfect. And then, because I was reading the Byetta board where Januvia was also being discussed, I discovered something really scary. The enzyme, DPP-4 that Janvuia inhibits is part of the system that our body uses to get rid of metastacizing melanoma cells. I'm a melanoma survivor (one of the very lucky few!)

So that was that. There was nothing in the research about this. You had to go to the gene studies about DPP-4 to discover the strong role it plays in suppressing melanoma, prostate cancer and a couple other cancers. I wrote to a scientist who had published the most about DPP-4 at the time and asked him if I was being paranoid. He said I was not and that it was strange no research had been done to check that out.

Now, 8 years later, there is more evidence coming out connecting Januvia with some really ugly pancreatic side effects, some of which could long-term be fatal. The drug companies did some damage control, all of it with studies that lasted 2 years--the same length of time that if you studied cigarette smoking, you'd conclude it was harmless.

So that is why as much as I am aching to get my hands on Afrezza, the saner part of my brain is thinking, Hmmm.

My current thinking is that if I did get some (which won't happen until it's approved by Medicare) I'd mix it with carb control and use it a few times a week to allow myself to eat some of the things I love that I simply can't eat without those spikes into the 200s. But I do have qualms about the idea of using it 5 or 6 times a day.

It takes about 14 years for the real problems with a lot of these drugs to become crystal clear. Coincidentally, that is when their patents expire and the drug companies have gone on to misrepresent other newer, more profitable drugs.

Some of these comments are border line ridiculous. Doctors who know their patients and are familiar with the product may feel free to have a patient try a sample for a week and get back to them.

Of course doctors won't be handing out samples to asthmatics and those with COPD. This is just dumb and I wonder why people who are clearly not going to use the product are on hear all day long making comments.

The insulin and DKP, or whatever the carrier is called, are fully transferred into the blood and utilized or peed out. Some Adcom members wanted to see some more animal testing where they take the lung rinse it out and test for residue. This was done years ago and we talked to a pulmonologist who had no issue with the product. People need to understand that the scientists at the FDA and industry are planning for dozens and dozens of new and old drugs to be inhaled in the next 20 years.

So is a heart or a pancreas or a foot for that matter.

The only real side effects after a decade of use was an initial cough in some users that seemed to subside over continued use. The insulin is regular human insulin and the carrier wing is well known chemistry. Since their seems to be little residue in the lungs, there is no real expectation of long term side effects.

Contraindicated for thouse with lung disease and smokers who have a higher likelyhood of Lung Cancer, but lung cancer is in alot of people and it takes decades to fully gestate.

Worrying about Lung Cancer with Afrezza is like worrying about prostate cancer from riding a bike.

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Casual dismissiveness about legitimate concerns like this is what gets people suspicious that people like you are shills for the investor community.

The fact is, insulin cross-reacts with Insulin-like Growth Factor receptors. This is not speculative -- it's a well-established fact.

Whether this is utterly benign in the case of Afrezza and pneumocytes or a potential long-term problem is a valid question, and concern.

The bottom line is there is plenty of good reason to say, "no, not a problem", hence the approval of the drug.

At the same time, it is also true that pneumocytes will be bathing in insulin concentrations many many many times higher than they naturally do, this insulin will have some binding signal with IGF-1 receptors, so what happens needs to be studied going forward.

We really won't know -- for certain -- until Afrezza users have lung biopsies after extended use (for whatever related or unrelated reason), and long-term Afrezza users die, so lung samples can be taken and studied.

Jenny - Thank you for bringing some counter-balance to all the Afrezza excitement. While I decided to use Afrezza, your experience and comments about the dynamics of big business, the FDA, and the real long-term health of patients give me pause.

We're not casually dismissive of anything. I spent an hour on the phone with one of the top pediatric pulmonologists in the United States, and to my surprise, she had almost no concern. In fact I would characterize her reaction as dismissive, and this was shocking. When practitioners with hundreds of juvenile and adult patients tell me not to worry too much, I take note. Also, I've used a sample pack, have you?

The Avandia disaster is one of the reasons that Afrezza has been so heavily tested in clinical trials. Avandia has made it much harder for metabolic drugs, but the FDA is much more predisposed to global companies with 10's of thousands of employees. If the Afrezza Advisory committee did not recommend the drug unanimously, it is not clear the FDA would have passed it.

Will, there is plenty of reason to feel confident about Afrezza. You're point about Avandia is important.

However, that doesn't mean that safety is a done deal now, and no future drug will have a completely unanticipated consequence stemming from a physiologic reaction that is entirely new, and therefore no one involved in approval even had the requisite knowledge or experience to question.

Coating Type I pneumocytes with insulin is just such a context where something like this might happen. It probably won't, but dismissing the concerns with statements like yours about prostate cancer and bike riding is neither informative, or helpful.

Sometimes I think Jenny is an alarmist. She does latch on to these reports of adverse affects and raises a red flag. If it was just Jenny reporting on some study, might not worry. Any information on a bad effect is probably the tip of the iceberg. The entire system is hopeless corrupt at this point. Ben Goldacre in his book "Bad Pharma" details how pharma companies are able to systematically manipulate regulators, doctors and consumers. The FDA only requires a certain number of positive trials, companies can just hide negative trials. Adverse events are a secondary element of the process, pharma companies routinely manipulate adverse events by doing things like "run in" stages where patients who have adverse effects are removed from the trials. It goes on and on.

I may not be as alarmed at Jenny but I don't trust the system and I usually won't try a new drug out of the starting get.

Not using a new drug right away is a reasonable pre-caution. Life is risky. There is no absolute safety, until you die.



My BG control before Afrezza was pretty darn good. It makes me wonder if I’m “gilding the lilly.” At this point, I will continue to trial it and make another decision after 90 days.



I am highly skeptical of the motivations of large corporations. I believe they are amoral, without conscience. I know they can provide wonderful products and services but I know they’re not doing that because they like me!

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Believe me, I get it. This was our first concern as well, but the scientific community is past this, for now. That is why the FDA is stats driven and it takes so long, to run the trials to get the stats. if the math suggests a risk, the FDA has to pounce.

Not doing clinical safety trials, in Avandia's case, is sketcy, but again, that is not the case for Afrezza.

What we need to now do is get alot of people to try Afrezza so their is a deep pool of information as to how well the product works, under what scenarios it works and for whom, and as importantly what scenarios and for whom it will not really make sense. That is where we are and that is the focus of threads started by people like Mike.

Using cancer as a bogeyman is a hot botton for me, becuase I know people who have it. The reality is that a large percentage of the population, almost all cronic smokers, have lung cancer at some state of development. Lung cancer can take upwards of 30 years to kill a person and my guess is that the vast majority of people on the Afrezza trials smoked at least at one point in their lives given its prevalence in our society.

Therefore, it is not helpful to make too much of 2 former smokers having lung cancer. There were two other people reoorted who had been in Afrezza trials years earlier that died of Cancer in their mid to late 60's-70's, but it is not clear what risks they had and one was a Russian women, so who knows. These levels of risk were about the same as a random person getting lung cancer.

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Therefore, it is not helpful to make too much of 2 former smokers having lung cancer

I agree 1000%!!

The best approach is to be impartial and factual. Exaggeration con or pro amounts to misinformation, regardless. Hyperbole is inappropriate when discussing drug safety and efficacy.

BTW, IIRC of the two cancers, one was a prior smoker... the other wasn't.

That irrelevant anyway. 2 cancers in a cohort of nearly 5000 is not statistically significant enough to rule out ideopathic cancer, for which there is a low "noise" rate among the population.

So those cancers, insofar as Afrezza, don't provably mean anything.

However, as with so many drugs that have been withdrawn, there are longitudinal effects that simply can not be "simulated" in any way in drug approval trials. This is what we'll learn about over the following years with millions of people using Afrezza.

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If they get a few million to try the product, that would be good for them, I am a bit skeptical that they will have millions using the product daily. But again, unless more people with T2 show results we just won't know. If it becomes a way to shut down pre diabetes without the hypo risk or weight gain due to the fast action and clearing, wow, that would be something. But we will see.

Interesting today, a study on MedPage was talking about a new standard for obesity being to treat the weight loss first and the comorbidities such as diabetes if weight loss drugs, diet and exercise do not work.

The medical community seems to be really worried about the side effects and costs of the newer oral T2 drugs.
Cannot wait to ask Hakken about this. Could see doctors prescribing Contrave for weight loss and Afrezza to control prandial glucose spikes until a person was at less risk of full blown T2.

One thing to keep in mind, if you are correct about a potential large user base. The FDA wants everyone to think about the drug before they use it and with the black box the people who undountedly will come down with problems if the product is used by millions will not be able to say they were not aware. I think this is a standard CYA for the FDA, and I also think Mannkind expected and likely welcomes that as well..

We need to be our own experts imo, we are the ones who will live with any adverse results. Experts have been known to be wrong and to make mistakes. The FDA has approved more than a few drugs and devices that have eventually caused serious harm to people and to furry people. These harms are often then denied after the fact but you will notice there is usually a legal statement somewhere about adverse side effects or potential harms which lets them off the hook.

Some of these drugs are still on the market, some are removed and some get re-cycled and put back on the market. For example while I was in dka in the icu they tried to give me a drug that had been taken off the market for causing arrythmia, at the time I knew it wasn't a good idea so I refused it. Due to the various complications I had it could easily have killed me.

I trust myself and my common sense more than anything else.

These are some of my concerns also. There were 4 cases of lung cancer in the afrezza trials, two in non smokers...

http://www.medscape.com/viewarticle/822957

"A total of 4 cases of lung cancer occurred in patients who had used Afrezza, 2 during the trial in smokers, and 2 others, both squamous-cell tumors, at 2.6 and 3.8 years after the end of the trial in nonsmokers. An oncologist on the panel, Liz Szabo, MD, from the National Cancer Institute, called that "unusual" and advised that more data be collected."