To see the full interview, click here.
Steve Freed: We’re here at the American Diabetes Association 77th Scientific Studies. And we’re here with a very, very special guest. I was just mentioning, he’s the type of guy that when he walks down the halls of these meetings, he never gets to where he wants to go, as everyone wants to talk to him, and probably forgets half the time where he’s going.
Dr. Bode: That’s probably true, I’m getting older.
Steve Freed: We’re lucky to have him here to ask some questions. He’s also known as the physician, the endocrinologist that knows everything in the world about pumps. You’ve been associated with some pump failures and you’ve been associated with some great pumps out there. I think that’s where we’d like this interview to go. Let’s start out with, in the pump industry, obviously pumps are very effective for type 1s and now we’re learning, probably for type 2s. So let’s first talk about the new artificial pancreas and your thoughts on that, because that’s supposedly making a huge impression. Although it’s really not an artificial pancreas, and maybe you can explain that. But really how do you feel about that particular product and where do you think it’s actually going.
Dr. Bode: So when you really look at the artificial pancreas. It’s really automated insulin delivery by a pump, based on the glucose readings from a glucose sensor. So you have to implant a glucose sensor underneath your skin with an insert. In this case, Medtronic has a new sensor, known as the Guardian 3 which is an 80% smaller sensor and much more accurate and precise. It has a MARD between 9.5 to 10.5% depends upon how often you calibrate it. But it’s also a new pump and it’s a pump that’s able to handle very advance software know as this algorithm auto mode or makes a decision every 5 minutes to bring the sensor glucose to 120. So if you’re below 120 and they’re trying to get you up. If you’re above 120, it’s trying to get you down. The other name for this is called a hybrid-closed loop because you need to announce meals. The only way you can announce in this system is giving grams of carbohydrate. But some people don’t even know what a gram is. You and I probably don’t know what a gram is either. But obviously it’s on the labels, but people need to learn how to carb count. The way this system works when you aren’t eating or at all times, if auto-mode is activated, you can tell by a blue shield. That means you’re always being driven down to 120. We have shown by doing so, and you announce meals by putting in grams of carbohydrate, we have shown that in a pivotal trial of 124 type 1s between the age 14 and 75, they had a .5 drop in A1C from 7.4 to 6.9. This was associated with less lows, less highs, more in range between 70 to 180. This was a safety trial, it was non-randomized. We had the safety endpoint was ketoacidosis and severe hypo and there was 0. In my take of this, it’s a game-changer looking back and if we look back 50 years from now, I’m not going to be here. You might be here, but unlikely. We’re going to look back, the discovery of insulin happened in 1920 but the next biggest step was automated insulin delivery, which happened in 2017, got launched then, because the reason why you can get to goal, you don’t have to worry about lows because you have this predictive low glucose to spend before you ever get to low, you shut off, you’re making a decision every 5 minutes. Every one day it’s a different decision at that time of day. At midnight, one time you could be getting one unit an hour, the next night it might be zero. Then at 12:05 you might be at .5.
Steve Freed: One of the questions that I’m sure you get all the time is: I don’t want to be attached to a machine that can kill me.
Dr. Bode: I certainly don’t want to be attached to a machine either that can kill me. This is why this was a safety trial. We didn’t have a randomized control group because the FDA’s all about safety. We wanted to make sure it was safe. The FDA did one other thing during this trial. They made us, for 6 days and 5 nights, take everybody and put them in a hotel. They have to exercise four hours a day. Some people never exercise one minute a day. We would have to have a physician there. Every night. We had to check their glucose before each meal, bedtime, midnight, and 3am. We showed that there was no hypo during that period either. So we did stress it for one week. So as a result of that data and since it was safe and appears to lower glucose in more time and range, they allowed it to come on the market.
Steve Freed: How many patients was that?
Dr. Bode: So, it’s 124 in the adult patients, adults being, sorry, 14 up to 75. So we had about 30 or so adolescents and the remaining 90 plus were adults.
Steve Freed: So that’s when you have 200 patients. What about when you have 2 million patients? The risk kind of goes up as far as finding there could be a greater chance to have serious issues with hypoglycemia. It’s very unlikely but it’s certainly a possibility whenever you deal with technology, something called Murphy’s Law, something always goes wrong. How do you respond to that?
Dr. Bode: So, when you really look and people say when you get a million people out there on this device. Are you going kill somebody from low sugar? Hopefully not, there are so many safe guard rails. People all the time with type 1 die of hypoglycemia. Typically the data is 6 to 10% of people will die of hypoglycemia right now. This hopefully will prevent that. We can’t guarantee it until we have lots of data but what we do have since the launch of this we have started the pediatric trial, 7 to 13, it’s still ongoing. It’s another 110 plus patients. We have people who have gotten early access. They bought the 630G so we have another 1,000 plus out there. If you look at the data in Care Link, because people upload weekly all the time, were told to upload weekly. The data from our Pivotal trial is mirroring, or the data from Real Time, another 1300 people plus, is mirroring what we saw in the Pivotal Trial. We have very rare time, less than .3% under 50, less than 3% under 70. We’re approaching a mean glucose right around 145 to 150. We don’t have any severe hypos.
Steve Freed: What if you had a young patient with type 2 diabetes and you think it would be appropriate to have his average below 120mg/dL? Right now I understand that the base level is now set at 120mg/dl. and cannot be changed?
Dr. Bode: So, as of right now, the next step, as you know people are frustrated being 120, you came in your A1C was 6, we allowed people in at 5 into this trial. They’d say, “I used to wake up at 80, but now I’m waking up at 110 or 115 and I don’t like that.” But I said, how about your lows? “I don’t have those anymore but I really want to wake up at 90 again.” Well, it’s going to be hard to wake up at 90. The next trial, where they’re making changes to the obviously there were bugs in the original software and those are hopefully cleaned up. The next step is sponsored by NIH, it’s called 690G versus 670G. The 690G is they’re putting in some fuzzy logic, known as MD logic, it’s how we prescribe meds and how we treat patients, it’s fuzzy, to the outsider. This is an Israeli algorithm. What they did, is if say you didn’t cover enough for your meal, you miss your meal, it will give you an auto-correction, continually trying to get it down to 120. Anytime, it’s always trying to get it down, even a correction bolus is down to 120, where now it’s at 150 when you give a correction bolus pricking your figure. Then they have some other fuzzy logic in there that maybe can be a little more aggressive but still right now at 120. If they want to go lower than 120, they’re going to have to go back and develop and go to the FDA and say we’re going to try this lower level. I think eventually it’s going to happen.
Steve Freed: Because 120 isn’t good for every single person.
Dr. Bode: No, and obviously the one contraindication to this is pregnancy. You want to be 80 to 90 fasting. Obviously if you get pregnant and you’re on this, you go back into manual mode, you can still wear the pump, but you need to have the sensor. You have this ability to suspend glucose before a low happens. That would be very beneficial also in pregnancy.
Steve Freed: Who are the candidates for this new “artificial pancreas”?
Dr. Bode: So as far as age goes, right now, by the label, it’s 14 and above. However, it’s contraindicated below 7 because they haven’t studied anybody. So you as a physician can write down to age 7 but it’s not in the label. We have several people on it down to age 7. We have even under 7 but by the label it says you should not prescribe it until it’s approved under age 7. The other thing is the system would prefer they think they need 8 units a day. So if you’re under 8 units a day total daily dose, they’ve never studied that either. They’d say wait until we figure out is that feasible.
Steve Freed: What has this done for the parents of children with type 1 diabetes?
Dr. Bode: So, for the parents of children, they will tell you a couple things. One, they don’t have to get up at night anymore because they know they’re always safe. Typically, especially young kids, they might go to bed at 8 o’clock at night and wake up at 7 in the morning and they’re always down at 120. It’s totally flat and very predictable because you’re in auto-mode there, it’s automatically, auto-piloted, just bringing you right down to 120 so they really like it. But during the day, the kids, they like to eat, especially when they come home from school all the way to going to bedtime, especially teenagers. You still have to put your carbs in and you don’t put your carbs in and you go above 300 for an hour or two or longer, it’s going to kick you out, it’s going to tell you to take a correction dose, to get you back in and under 300. So, during the night it’s a miracle to the parents. During the day, they have to calibrate the sensor and if it’s a lost sensor, they have to calibrate and find out why it’s lost. If they need to change it, they got to change. But if you just follow what it says, it says glucose, check the glucose. If it says change the sensor, change the sensor. You always have this safe basal. If the sensor is lost, you go into a 90 minute period where you have a safe basal that the algorithm says this will be safe, you shouldn’t go low, you shouldn’t go high until you can get your sensor working again.
Steve Freed: So, when you graduated med school, had you thought about this?
Dr. Bode: When I graduated medical school, I did think about this, I had developed back in Cambridge, we were working on an insulin pump in 1974. So when I graduated medical school, we were playing with automatic IV insulin titration. Did I think this would happen? No, but I said in the future, we didn’t have sensors there, all we had was point of care blood sugars. Once we knew there were sensors there, that we could do, that came out in 1999 from John Mastrototaro. He’s the first person in the world that developed a glucose sensor that was approved by the FDA. Glucose Oxidase. We knew from there, once we could predict it, we could go into closed loop.
Steve Freed: Let’s change the topic a little bit from pumps to CGM. How big of a deal is that?
Dr. Bode: So, having CGM out there as you know, Continuous Glucose Monitor systems are improving all the time. Every time I come here, there’s something better and every time I come here I see three or four new type of systems in development. These are phenomenal. As you know Dexcom is going for an indication of a 10-day sensor with one calibration a day and a much smaller transmitter. That’s great. We got Abbott Libre Flash, which has a professional sensor, but it’s a small little disk that the transmitter’s disposable and you don’t have to prick your finger. That’s not approved in the U.S., but it’s approved in Europe and there’s over 300,000 people paying cash for it. You come to these meetings now and you look at other sensors. I looked at a sensor that goes right underneath your arm. It’s the size of a kernel of corn. It’s an optical sensor. It’s in the MARD of 8%. Right now, they’re hoping to get approval for 90 days in the U.S. but they’re pending approval for 180 days in Europe. They’re working also over in Europe on a one year sensor and you might calibrate it once a day or maybe twice a day or hopefully eventually once a week. Or maybe twice a month. Another sensor that was there and it was one year sensing and it’s powered, everything is powered and it’s giving off a signal completely all the time. You still calibrate it but they hope to calibrate it once a week. If that can happen, you have continuous sensing, that’s a game-changer.
Steve Freed: Do you think that will basically take the blood glucose monitoring company pretty much out of business? If the prices are at least comparable?
Dr. Bode: For blood-glucose monitoring, if these become comparable to pricking your finger and it’s comparable in price, why would somebody prick their finger? Pricking your finger is painful. I don’t like pricking my finger, but people with diabetes, once you prick it 1,000 times it doesn’t hurt anymore. Sensors don’t really hurt that much going underneath the skin. I think you’re always going to have point of care testing, both for diagnostic in the clinic, you prick their finger when they come in, making sure they aren’t low and high, but then also people who have just mild type 2 diabetes, they just want to check once a week and they’re borderline, they can do that instead of using a CGM. I think there’s a role for both. But it has to get down in price, sensing. Right now, the Abbott Libre Flash, it’s inexpensive. It’s 14-day sensor, 50 euros for two weeks. If you can get down to $4 a day or $3 a day, that’s very inexpensive.
Steve Freed: Your kind of interested or excited about things that are coming down the pipeline that you know for sure, most likely are going to get here, they’re just waiting to do their final things and submit it to the FDA, so it’s actually here, we’re just waiting for approvals and things like that. How is that going change your practice?
Dr. Bode: I think in our practice in really the masses once we have CGM and we can easily put them on them and see what’s going, the patient will come back and say “Doc, you know, every time I eat cereal in the morning, I’m going really up, but if I have bacon eggs, that’s not good for my heart, my sugar’s flat.” Cereal has a lot of carbs in it, especially if you’re eating cereal, you got sugar cereal, Cracker Jacks, or whatever you’re doing, you’re going to come up. So people can learn what foods bring them up. A lot of people say “Jeez, when I eat pizza I go up but then it stays up all night long. What’s that? What causes it?” High fat foods cause marked insulin resistance. So people will learn when they see their sensor. But the sensor reading is right in their phone. Everybody now, you go down to the airport, everybody’s looking at their phone going down. On a busy sidewalk, everybody’s looking at their phone, so the sensor’s always there; people can see there it is.
Steve Freed: So where are you right now when it comes to type 2s? Maybe not on insulin, just maybe on oral medications as far as using maybe the Libre system or even the Dexcom system. If they’re willing to pay cash, because most insurance companies aren’t going to pay for it?
Dr. Bode: So, we do professional CGM and we give them a Dexcom or an Abbott Libre Flash, so if you aren’t at goal and we don’t know what’s going on, we need to figure out is it meal excursions, is it just one meal when you binge? Or is it overnight? Is it the liver putting out too much glucose? Once we figure when they’re going high, we can figure out what best drug we should use, or behavior change. So, if it’s just three times a week they’re going up to 400, you say, well what are you doing, they say I have a bad problem, I eat a whole box of Oreos with ice cream, but only three times a week. I say why don’t we give you insulin for that if you can’t do it? CGM will give you a good profile of what’s happening at all times.
Steve Freed: If you had your druthers, would all your diabetic patients be wearing some kind of CGM? With all the wristbands and all the motion detectors?
Dr. Bode: I think if you have the ability and as you know, Google is getting into this and other companies. Obviously, these people like data. They like to know what data is going on. I think if you look at your phone and know what your sugar is at all times, you can make educated changes in your behavior to eat healthy. If you exercise, you say “every time I exercise I’m down in the 90s, when I’m not exercising I’m 120.” Maybe it will get people to exercise and stay fit. If they do that, not only do they live longer and healthier, from a health care standpoint, there’s a marked reduction in total cost of care.
Steve Freed: So it’s really a change in the way you practice medicine?
Dr. Bode: Yes, it is, it’s been changing it for a long time and we’re right on the front at all times.
Steve Freed: So if you had to say, it’s been very positive for you?
Dr. Bode: Yes, it’s been very positive. The advances in technology, not only in pumps, but we also have better insulins. We have better glucose testing machines, especially CGM. We have better oral agents coming out. There’s many things happening. We’re even working on an oral GLP-1. Things like that. These are all game changers that are going to help everyone improve diabetes care.
Steve Freed: So you spend how much of your time in the research aspect and studies, compared to sitting with patients?
Dr. Bode: Every day I sit with patients. If I’m in the office, I’ll see typically I never see more than 12 to 15 patients a day. I do half-hour follow-up, hour for new. In between that I have 11 research coordinators full-time. I have a research director. I also have working with us, we have five endocrinologists and we have 11 physician-assistants and nurse practitioners. We have a lot of people and we keep people busy and every year we have more people coming to see us for diabetes. If they’re ever interested in a research trial, if they’re a candidate and they’re willing to do it, we have a trial for them.
Steve Freed: I thank you for your time. If I could, I’d have you sit here for a couple of days. I could come up with a lot more questions. Hopefully we’ll see you at AACE, I presume?
Dr. Bode: Thanks for an interesting conversation.