I like these quotes:
So what we have been trying to do is try to get insulin to be quicker. So what you have is regular insulin, that you can see here (slide), that it's relatively slow. It almost looks like NPH. Rapid Acting Insulin is much quicker. It doesn't last as long. So Regular Insulin lasts up to 8 hours, Rapid Acting Insulin lasts upwards of 4 to 5 hours. We are trying to get a more physiologic insulin, very similar what the pancreas does, releases a lot of insulin in the first 15 minutes, and that's the goal of Ultra Fast Insulin. And so everyone with Diabetes has lost First Phase Insulin Secretion, everyone. All Type 2s, all Type 1s. So you like to try to do that, to really shut the secretion to glucagon down from the (Alpha) Cells, to give yourselves realistic options. So obviously, early insulin secretions plays a major role in controlling Post Meal Glucose. It does it by decreasing Hepatic Glucose Production. And this is certainly a deficit in all people with diabetes. So this is a study about 7 years ago, looking at Lispro versus Gila Insulin. And they wanted to know did Lispro really control Post Prandial Glucose. So it did it by suppressing the Post Production. And so when it was able to suppress that glucose production, the post meal rise was less. And that's the major action. So, as you know, when you look at Rapid Acting Insulin against Human Insulin, they have a lot more insulin, whether its Lispro or Aspart Glulisene. We had better post meal control. We didn't have any difference in A1C. Oh yeah, the meta analysis showed a .1 drop in A1C. But people could dose insulin with the meal, and if they were uncertain, it's not ideal, you can dose at the end of the meal.. They got approved for that. And there was less nocturnal hypoglycemia, not daytime, less nocturnal. So knowing all this, people have been trying to develop a faster acting insulin.
Dr. Bode:
"One of the advantages of inhaled insulin (AFREZZA), you offer it to anyone that is relatively short duration into their diabetes, less than one or two years. A 100% will come back and tell you, I really like this. I can take it. I don't go low and I don't gain weight".Dr. Bode: The problem is most people (ENDOs) out there, never give this (AFREZZA) an option. They worry about the pulmonary safety opinion. They never worried about pulmonary safety, but that's their job. Their job is to make sure that whatever medication you give that that it's safe. And there's clearly, from Lung Biologists and Pulmonologists and Oncologists, the (AFREZZA) is safe".
Q: What do you give when a patient doesn't like the inhaler because of the cough / feeling of stuff at the back of the throat.
Dr. Bode: R: So this is the most common side effect. It happens immediately on the first inhalation, and there's several ways to overcome this. Some is one, take a drink of water. Make sure your mouth is not totally dry. Some are not aiming it right, they are aiming it more back up top causing a reflux, and it's no different to taken albuterol. So if you take Albuterol, you will have had some type of cough sensation. But after the 3rd or 4th inhalation, people learn to tolerate it . They have to do it 3 or 4 times. But most of the people quit after the 2nd or 3rd inhalation, "I don't like this,the sensation of that something going to the back of the throat causing the cough". Long term, cough dissipated dramatically and nobody ever complained about it. But it all happened in the first week or so of initiation. And so this was true in the Type 1 study. Typical, dropped out after the 3rd or 4th one, but the others figured out what to do, and you can go to the Blogs (AFREZZA) and just Google Cough, people will tell you , drink a glass of water before you inhale , making sure you have some moisture in it. It's not a major issue.
Dr. Jeremy Pettus
The only thing I've noticed, is that people , when they first start to do these dramatic inhalations, they suck vigorisly and really, I feel that they can produce a cough. But it really does not take a lot of force. It's more a calm, kind of like gentle inhalation and still get the amount of material. Like Bruce said,
I wanted to say, most people used, you will most likely cough for the 1st or 2nd time, but then it goes away.Dr. Janet McGill
Yeah, you read e-mails. People do overdo , you're right. Have them calm down a little bit. Aim (inhaler) that it does not hit the top ( of the mouth).....(aim for the throat).
CHANGE OF INSULIN
Dr. Janet McGill
Patients tolerate: change the insulin, restart the engine. Patients tolerate a few more units because it's gone so quickly, so control of these prandials.
Try it out as this: Initiate as a Correction Only, that you did not overshoot and go low. That would open the door for many people to say, "gee, this is kind of interesting", and just use it as a correction dose to get it back down and let them use it for snacks, let them use it for this or Basal with Inhaled (AFREZZA) only.
"We use it (AFREZZA) also on our exercisers, who really cannot handle a tail on their insulin. Some of them are wearing some pumps and use the inhaled insulin (AFREZZA) for both meals and corrections, because the tail effect is a big problem for them.
Dr. Jeremy Pettus: Question: So next one is - Are Lung Function Tests required - Full FPTs or just FEV 1.
Reply Dr. Janet McGill: Just FEV1
Reply Dr. Bruce Bode: So in the development phase, they did full function initially, and realized, the FDA realized this, the Pulmonologist consultants said, you don't need to do this, just an FEV1, and that is very quick. Obviously, Primary Care Doctors do it, obviously Pulmonologists have them all the time. But Endocrinologists don't have them, they think it's a very big thing. It's so easy, it's a very inexpensive kit. You can buy hand held ones that are very inexpensive / disposable.
But why do you want something disposable when you can buy something for $1000 and you can use it on hundreds and hundreds of patients. You get reimbursed, but its not much, it's $30, I don't know, it's about $30 or $40, but you will have it it payed for almost immediately. So we do about these. It only takes our staff 3 minutes. What's the length of doing that. Typing in the name and the date of birth and their weight. They do it 3 times and get the average.Question: Safety of Inhaled Insulin (AFREZZA)
Reply: Dr. Bruce Bode: One thing, I think, is the safety. Most ENDOs won't prescribe because of the safety. I have been around enough of these lung biologists and experts, because I've been involved with them for the last 10 years. They'll convince you "it's perfectly safe". And the other thing, this drop of 40 mililiters, it's like me sitting here and I go back like this, I drop 40 mililiters of my FEV1 by just lying down. That's less that one per cent, one and a half per cent of your FEV1 overall. Lung Function: That's the safety. But that's hard for people to get over. And then the big thing is: People are, especially Type 1s, that are stuck on their 4 and 8 units; "I use the half unit here, the 2.5 units there. Tell them, it's in and out so quickly, it's gone so quickly. The hypoglycemia is related to, from Hour 2 to Hour 5. People going low before lunch all the time, people going low in the afternoon, people going low early in the bedtime and they are eating, they are going low at bedtime ad they eat a bunch of food. They are high and they are taken insulin, and they are over-correcting and they go low. This (AFREZZA) is in and out so quickly.
Initially on the market back in the 1920s, nobody would have ever taken a SubQ Insulin for meals, never! But unfortunately, everybody is used to SubQ Insulin, and that's all they know. They have this precise carb in ratio on their pumps. And
in our Hybrid Closed Loop development, the group out of Santa Barbara, did a trial using inhaled insulin (AFREZZA) versus rapid acting insulin Lispro in the Artificial Pancreas Project. In the inhaled insulin, totally flattened out the meal rise and it did not have any reactive hypoglycemia. Question: Give the latest post marketing data on lung cancer:
Dr. Bode, Reply:
"As far as I know, there's no reported (cases). The ones' who had lung cancer, there were a total of four, 2 during and 2 afterwards. These people - 2 of them had long standing history of smoking. One person only used it (AFREZZA) a very short time, less than a few weeks. So you know, obviously, so many people think this rate of lung cancer of these 4 cases is so unexpected. They also showed that when they looked at the Chest xRay, 2 out of the 4 had changes on their xRay that was misdiagnosed unfortunately. So there's no way that inhaled insulin can cause cancer within. You know, 10 weeks, 20 weeks, and this thing (AFREZZA) doesn't hang out in the lungs. There's no activity in the lungs. So it just either gets absorbed. If your's silly, bring it back up and cough it out when you swallow".
