#1217 iLet from Beta Bionics

Steven Russell, MD is here to talk about the iLet pump from Beta Bionics.

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DISCLAIMER: This text is the output of AI based transcribing from an audio recording. Although the transcription is largely accurate, in some cases it is incomplete or inaccurate due to inaudible passages or transcription errors and should not be treated as an authoritative record. Nothing that you read here constitutes advice medical or otherwise. Always consult with a healthcare professional before making changes to a healthcare plan.

Scott Benner 0:00
Hello friends and welcome to episode 1217 of the Juicebox Podcast.

Today I'm going to be talking about the islet insulin pump with the Chief Medical Officer of beta bionics, Dr. Steven Russell. Dr. Russell and I will go over questions from the audience as well as his feelings about the eyelet pump. Nothing you hear on the Juicebox Podcast should be considered advice, medical or otherwise, always consult a physician before making any changes to your health care plan. When you place your first order for ag one with my link, you'll get five free travel packs and a free year supply of vitamin D. Drink ag one.com/juice box. If you are a loved one has type one diabetes and you are a US resident. I'm asking you to take 10 minutes to fill out the survey AT T one D exchange.org/juice. Box completing that survey helps significantly with type one diabetes research. T one D exchange.org/juice box. If you're looking for community around type one diabetes, check out the Juicebox Podcast private Facebook group Juicebox Podcast type one diabetes. And as a matter of fact, we have quite a few users using the islet pump so if you have questions, join the group is absolutely free. This show is sponsored today by the glucagon that my daughter carries G voc hypo Penn Find out more at G voc glucagon.com forward slash juicebox. This episode of The Juicebox Podcast is sponsored by us med U S med.com/juice box or call 888721151 for us med is where my daughter gets her diabetes supplies from and you could to use the link or number to get your free benefit check and get started today with us met. Today's episode is sponsored by Medtronic diabetes, a company that's bringing people together to redefine what it means to live with diabetes. Later in this episode, I'll be speaking with Jalen, he was diagnosed with type one diabetes at 14. He's 29. Now and a little later, he'll tell you about his life with type one. To hear more stories with Medtronic champions. Go to Medtronic diabetes.com/juice box or search the hashtag Medtronic champion on your favorite social media platform.

Steven Russell, M.D. 2:39
Hi, this is Steven Russell. I am the Chief Medical Officer of beta bionics. I am also a associate professor of medicine at Harvard Medical School and I see patients at the Massachusetts General diabetes Center part time but most of my time now is spent working at beta bionics. I have been working on the bionic pancreas project for about 16 years now been working with that Damiano. And for us Alkhateeb from the early days of the bionic pancreas project and, and directed most of the clinical studies that were done three pivotal and pivotal and joined the company in the end of 2022 to help to get the product approved by the FDA and prepare for launch.

Scott Benner 3:28
Okay, so you have a good, healthy, long relationship with it. So you're gonna have all the answers, right? Some of them well, I'll do my best. What's your educational background?

Steven Russell, M.D. 3:38
So I have an MD and a PhD in biological chemistry. And I trained at UT Southwestern for my MD and graduate degree. And then I came to Massachusetts General Hospital for my internal medicine residency, and stayed at Mass General Hospital for an adult endocrinology fellowship. Okay, so

Scott Benner 4:00
did you do most of your work in endocrinology, or is it internal? So

Steven Russell, M.D. 4:04
endocrinology is a subspecialty of Internal Medicine. So you have to do internal medicine residency first, okay. And then you can sub specialize and I chose to sub specialize in endocrinology.

Scott Benner 4:16
I always like to know what made you choose it? Well, I

Steven Russell, M.D. 4:18
think it's partly the kind of work it's you know, diagnostic work, solving puzzles, but also long term management, you know, trying to figure out how to help people live their best life with diabetes is appeal to me. And from the research standpoint, I've always liked intellectually curious, I like the fact that in endocrinology, there's control loops, that are sort of intellectually satisfying. And so that was appealing. For that reason, I think, and I knew I wanted to do some research, and there's just this great history of research that comes out of endocrine I think something about hormones, they were accessible to work on, early on. If you identified a hormone, not only did you have the hormone but you that you had a drug, you know all almost all of those hormones were also immediately usable as drugs didn't have to go find a small molecule. So when insulin was discovered as the key element to control glucose, all you had to do was purify the insulin, not a trivial matter, but you had to purify it, figure out how to use it, you didn't have to then go and find some other small molecule drug that could act on the insulin receptor. It's a, perhaps a shorter path from figuring out how the mechanism works, to being able to do something with that information to help a patient. Okay,

Scott Benner 5:45
so then is it fair to say that those things that light you up are maybe one of the reasons why somebody came and found you for for this 16 years

Steven Russell, M.D. 5:54
ago? Well, we sort of found each other. So Edie had started to work on the bionic pancreas algorithms, because, as his well known now, he had a son who developed diabetes at 11 months of age. He was an applied mathematician doing fluid mechanics, but thought maybe he could use his applied mathematical skills to to improve management of diabetes. And he was to the point of doing studies in pigs that he made diabetic with bras and they were doing these studies with an earlier version of the algorithm. And he came to the Joslin diabetes Center to report on that work. And I was there doing a postdoc trying to understand how insulin signaling effects longevity and aging. But I also had a side project looking at accuracy of CGM and in people in the hospital and critically ill. So we reported these data using both insulin and glucagon. And I really liked that approach. It was kind of contrarian at that point, because people said you couldn't use glucagon as part of a control strategy. And sometimes when people say something can't be done, it's true. But in many times, they they just haven't opened their mind and really investigated it. So I was intrigued by that possibility. So I approached him and said, hey, you know, you're doing these animal studies? Could we work together to do studies in humans, and he was enthusiastic about that prospect. And from that point onwards, we started writing grants and planning studies, and, and we've been working together ever since it's

Scott Benner 7:37
interesting. It's interesting how you can ask a question, and somebody will say, No, absolutely not. Or maybe, and, you know, like that the No, absolutely not people like, are they so tied to what they know that they can't see the rest of it? Is it just comfortable for them? It must make all of these things difficult in an academic setting, right? Because so many people tie their ideas to who they are. You know what I mean?

Steven Russell, M.D. 8:04
Absolutely. I mean, if somebody has been working on insulin, only automated insulin delivery or insulin only automated glucose control for a long time, and then you come in and per proposing using a second hormone. I think that that can be kind of threatening. Yeah. And can feel like, oh, wait a second. You know, you're you're encroaching in my territory. This, we're going to do this this way. Right. At one point, I had somebody not to be named come up to me and say that nobody should be working on by hormonal glucose control until there was an insulin only system on the market. And I thought that doesn't make a lot of sense to me. I

Scott Benner 8:49
know someone told me one time that I couldn't make a podcast and talk about how we manage my daughter's blood sugars. If you take insulin or sulfonylureas you are at risk for your blood sugar going too low. You need a safety net when it matters most. Be ready with G voc hypo pen. My daughter carries G voc hypo pen everywhere she goes because it's a ready to use rescue pen for treating very low blood sugar and people with diabetes ages two and above that I trust. Low blood sugar emergencies can happen unexpectedly and they demand quick action. Luckily, G voc hypo pen can be administered in two simple steps even by yourself in certain situations. Show those around you where you storage evoke hypo pen and how to use it. They need to know how to use Tchibo Capo pen before an emergency situation happens. Learn more about why G vo Capo pen is in Ardens diabetes toolkit at G voc glucagon.com/juicebox. G voc shouldn't be used if you have a tumor in the gland on the top of your kidneys called a pheochromocytoma. Or if you have a tumor in your pancreas called Have an insulinoma visit je voc glucagon.com/risk For safety information. And now 17 million downloads later, it helps people in 48 different countries. So if I were to listen to that person, none of this would have happened. So here's the people who don't listen. That's great. So now we've got a fast forward all this way you go through this entire process, you get a device, it gets its way through the FDA, it's it's available on the market now. I always, when I'm thinking about it, let I want to know if I am. If I'm clearly understanding what it is. And I'll just tell you that from my perspective, it seems like a fantastic device. If someone has an elevated a one C, and struggles and can't figure things out about how to dose or count carbs or anything like to me this seems genius. I mean, if you're a person walking around with a 1011 1213, a one see, are you telling me I can put the eyelet pump on and announced meals? Like I mean, what are the announcements? It's snack? How was the

Steven Russell, M.D. 11:03
Wreckfest? Lunch or dinner and usual for me more or less? Okay,

Scott Benner 11:07
so I make those two announcements. And I get an A one see where? Well,

Steven Russell, M.D. 11:13
on average seven, about half of the people in our pivotal trial wound up with agencies below seven and about half above seven, and most of those were below seven and a half. Okay,

Scott Benner 11:25
that's astonishing. So that did. So that's my point. For every person who listens to this podcast and firmly understands Pre-Bolus eating their meals and adding insulin for fat and protein and all the other things that you need to understand to keep stability. I mean, I don't know the number, but there's got to be 100 people who don't understand it are never going to even intersect the information that if they did, they might not get it. So am I thinking about that right? Or am I undercutting islet? By thinking about it that way?

Steven Russell, M.D. 11:49
I think you are under cutting a little bit, I think you're right. It's definitely great for people like that. And we wanted it to work for people like that there's a lot of people out there who aren't being served by the current or previously available diabetes technologies before islet. And we know that that's the case, because only 20% of people in the US with type one diabetes at expert centers have an A one c less than 7%. So that's a pretty sobering statistic. The average a one sea of people with type one in the US is about 8.2%. So that tells you that the current methods are not sufficient. And that hasn't changed. By the way very much as we've gotten CGM and AI D. I think a lot of new technologies that we've gotten have allowed people who are already had pretty good glucose control to get even better glucose control. But what they haven't really done is allowed people who weren't getting good glucose control to get good glucose control. And I think that's where the islet is, is really different. One of the ways that the sense that I think you may be underselling it is even people who have good glucose control, are often spending more time managing their diabetes than they would ideally like to do. There's an enormous mental overhead associated with managing diabetes just takes a tremendous amount of thought and effort and time and consideration to achieve those kinds of results for even for the people who are achieving good results. And I think that there's a real opportunity for those people to continue to get good results. But with less effort on their part, what we found in the pivotal trial is that for people who already had an agency less than 7%, at baseline and the trial, their average a once he did not change on the eyelid. So if they had an agency below 7%, on average, they still had an agency below 7% was about six and a half percent for people on the island for people who already had an agency below seven. Okay. And they did that with a lot less effort. And you don't really capture that in the in the numbers. But we did do patient reported outcomes where we asked people using these standard sorts of questionnaires, essentially, how are you feeling? And what we found is that they had less diabetes related distress, less fear of hyperglycemia, better quality of life. And those are things that don't show up in those agencies or those average glucose numbers but are real and matter. And

Scott Benner 14:40
so are you saying that people who had a better understanding to begin with, generally speaking didn't see a rise in a one see when they moved to Island?

Steven Russell, M.D. 14:48
That's true. Yeah. What we did see is that as I said, on average there anyone see didn't change on the eyelid if they started off already meeting goals for therapy if they already had anyone see less than 7% And if you break it down further and look at that group, some of them had no change in their agency from baseline, some actually saw further decreases in their agency on the eyelet. Some actually saw increases in their agency, although by and large, they still stayed below seven. But what was interesting about those people who saw rises in their agency, they generally had significant reductions in their time less than 54. So they were seeing an increase in their agency, because they were having a lot fewer lows,

Scott Benner 15:31
people who were coming to their agency, sort of, not honestly, right, like they it was being offset, their standard deviation was being offset by low blood sugars.

Steven Russell, M.D. 15:39
That's right, okay. And on average, the eyelet didn't change the amount of time less than 70 or less than 54, there was no difference in the control group and the islet group, and time less than 54. Median was point 3% of the time less than 54. And that was true in both groups. But that does conceal a little bit that conceals interesting things. So for people who had very high levels of hyperglycemia, at baseline, the eyelet, decreased them quite a bit. For people who had none at baseline, it tended to increase it a little bit from say zero to point 2% of the time. And that might be the cost of you know, somebody having an agency of 10 or 11, or 12, with zero hyperglycemia, you bring them down to an agency of seven or seven and a half, they're going to have a little bit but still acceptable amounts. And then people who had hypoglycemia below 1%, at baseline, typically no change.

Scott Benner 16:38
Okay, so I have a ton of questions here. And if you don't mind, I don't I don't mean rapid fire, like we're going to be exhausted and sweating when it's over. But I'd like to maybe lose the conversational nature of this a little bit and go to more of a question answer if you don't mind. Of course. Okay, that's excellent. Thank you. Let's start with kind of the basic stuff. Let's just start with dosing. Like you just said, breakfast, lunch, or dinner. So you you pull up your pump and say, hey, it's breakfast, and I am having an average meal for myself, do I Pre-Bolus that,

Steven Russell, M.D. 17:09
we suggest that you announce the meal at the time you're starting to eat

Scott Benner 17:14
it. So that's a no then to the Pre-Bolus. Right? If

Steven Russell, M.D. 17:17
you are some people really like to do that and find that, you know, they might get some people say that they get better glycemic control less of a postprandial excursion. If you're going to do that, though, you need to do it consistently, because it will affect how the islet learns how much insulin you need for that meal.

Scott Benner 17:34
Okay, let me jump to that word, then learn what is learned mean, in regards to eyelet? How does it learn? What is it do with that information? How does it change the future?

Steven Russell, M.D. 17:44
Sure, it depends on which part of the insulin dosing you mean. So there's basil, there's a basil algorithm that learns, there's a correction algorithm that learns. And then there is the meal dosing algorithm that learns, and they, it is unique in that all of those do truly adapt and learn the individual's insulin needs. Most of the other AI D systems don't actually adapt or learn anything. The one exception I would say would be Omni pod five, because it it does actually determine the basil dose, it updates it every time you change a pod based on the average basil for the previous pod. But all of the other systems and all the other aspects of Omni pod five, are just reacting to the circumstance at hand, right? It's not changing how it doses in the future. But with the island, it truly is learning and adapting. So you ask about the meal doses, what we do is for each of those meal types breakfast, lunch and dinner, which are which adapt independently of each other. The island initially the first time you announced a meal, it gives just a very small weight base dose, which is point o five units per kilo. So if you're an 80 kilo person, it would be roughly four units, which for most people isn't enough, then what it does is the corrections algorithm automatically provides additional insulin to correct the blood glucose back down to the target. And it keeps track of how much insulin it needs to do that over the next four hours. Then the next time they announced another say usual for me breakfast, it looks back at that previous meal and say Oh, I gave for at the beginning but then I had to give another for correction. So it looks like a usual for me breakfast needs eight units, and then the eyelet gives 75% of that. So six units. Again, that's because we want usual for me to be most of the meals we want it to be a range so that people aren't counting carbs or just qualitatively estimating. And then the next meal keeps track of additional correction insulin maybe this time it uses a total of nine units. So the next time You announced the usual for me breakfast, it averages those two previous meals. And it keeps doing this up to seven meals. And so it's constantly looking at the average of the insulin dose it thinks you needed for the last seven meals once a day, once a day to as eight days old, it's forgotten, and you've brought a new day in. So we're always looking at the average amount of insulin needed for a meal announced that way over the last seven days. Okay, we give 75% of that.

Scott Benner 20:28
What happens if in the middle of that week, I throw a breakfast sausages or bacon in with my meal that I haven't had before. And suddenly my digestion slows down. It'll address that as a higher blood sugar when you get the fat rise. This episode is sponsored by Medtronic diabetes, Medtronic diabetes.com/juice box. And now we're going to hear from Medtronic champion Jalen.

Speaker 1 20:51
I was going straight into high school. So it was a summer heading into high school was that particularly difficult, unimaginable, you know, I missed my entire summer. So I went, I was going to a brand new school, I was around a bunch of new people that I had not been going to school with. So it was hard trying to balance that while also explaining to people what type one diabetes was. My hometown did not have an endocrinologist. So I was traveling over an hour to the nearest endocrinologist for children. So you know, I outside of that I didn't have any type of support in my hometown.

Scott Benner 21:25
Did you try to explain to people or did you find it easier just to stay private?

Speaker 1 21:30
I honestly I just held back I didn't really like talking about it. It was just it felt like it was just an repeating record where I was saying things and people weren't understanding it. And I also was still in the process of learning it. So I just kept it to myself didn't really talk about it.

Scott Benner 21:45
Did you eventually find people in real life that you could confide in. I

Speaker 1 21:49
never really got the experience until after getting to college. And then once I graduated college, it's all I see. You know, you can easily search Medtronic champions, you see people that pop up and you're like, wow, look at all this content. And I think that's something that motivates me started embracing more. You know how I'm able to type one diabetes, Medtronic

Scott Benner 22:10
diabetes.com/juice box to hear more stories from the Medtronic champion community. I used to hate ordering my daughter's diabetes supplies, and never had a good experience. And it was frustrating. But it hasn't been that way for a while, actually for about three years now. Because that's how long we've been using us med us med.com/juice box or call 888721151 for us med is the number one distributor for FreeStyle Libre systems nationwide. They are the number one specialty distributor for Omni pod dash, the number one fastest growing tandem distributor nationwide, the number one rated distributor in Dexcom customer satisfaction surveys. They have served over 1 million people with diabetes since 1996. And they always provide 90 days worth of supplies and fast and free shipping. US med carries everything from insulin pumps, and diabetes testing supplies to the latest CGM like the libre three and Dexcom g7. They accept Medicare nationwide, and over 800 private insurers find out why us med has an A plus rating with the Better Business Bureau at us med.com/juice box or just call them at 888-721-1514 get started right now. And you'll be getting your supplies the same way we do?

Steven Russell, M.D. 23:42
Well, there's going to be really two effects of that right. One is that it may slow down the absorption of the carbs. But it may also make you have to get more insulin ultimately, because the fat is interfering with the action of insulin. That's part of the reason that we only give that 75% Because we don't want to overdose right up front. If somebody eats on the lower side or for instance, eats something that's going to slow down their absorption. So we tell them not to consider the amount of protein not to consider the amount of fat. That's part of why we're conservative with that initial dosing knowing that our corrections algorithm can come in and fill in any gaps. So there's an element of adaptation. It's learning how much it thinks you need, but then we're only giving three quarters of that. And then there's an element of being reactive to how this meal might be different from previous meals. Because the correction algorithm it doesn't, you know, give 75% and then give the other 25% it gives 75% And then just sees whether more is needed. Maybe none will be needed, or maybe it'll be needed later in that four hour period than earlier because they had more protein. If

Scott Benner 24:54
I flip that on its head then and I eat that fattier meal to three days in a row and then the fourth day I just I have the same amount of carbs, but just nothing that's going to slow down digestion am I going to see a low blood sugar there?

Steven Russell, M.D. 25:04
Well, if you have nothing that's going to slow down the absorption, the glucose may be absorbed faster, you may get a sharper spike, actually. And so the correction algorithm may jump in sooner to give more correction insulin, but then, because there's no fat or protein slowing it down, it may not need to give any more after that initial dosing. But

Scott Benner 25:26
in that situation, if the carbs are the same five days in a row, the first four are fat laden. And so it's it's correcting, correcting correcting on the fifth day, does it not think breakfast is going to need more? And then suddenly, it doesn't is that's where I'm asking. Like, almost like with Right, right? Yeah,

Steven Russell, M.D. 25:42
but that, but that's part of why we only give 75% That's what helps that? Yeah, exactly. Okay. Yep.

Scott Benner 25:48
It's interesting. Now what happens? I mean, do you see I guess the question should be, do you see in testing or with real life use high blood sugars that it just can't affect? Like, what happens when a person who's used to taking care of their blood sugar's looking and saying, God, I have been to 50 for three hours, I want to Bolus here like what are they supposed to do then?

Steven Russell, M.D. 26:09
Right, I think that does sometimes happen early on before the meal doses have had a chance to adapt. So it's almost by design, that you probably if you're somebody who needs more insulin than that sort of low initial estimate, almost by design, you're going to see hyperglycemia after that first meal. And the island needs to see that hyperglycemia to give correction insulin to know that you're going to need more insulin next time. Okay. And so if you are patient and wait, and assuming your infusion set is working, and it hasn't failed or anything, the the eyelet will bring your blood glucose back down into range. And then the next time you announced the usual for me breakfast, it will increase the amount of insulin that it gives you for that meal. So you do have to be a little patient over that first day, or two or three or four days in some cases, or the islet to learn how much insulin you need and to adapt up and if you short circuit that process by say, I can't stand this my blood glucose 250, I'm gonna have to do something. Let's say you give insulin that the island doesn't know about, you give an injection and the island doesn't know that you gave that injection. Now the island doesn't think you need more insulin. So the next time you announce a meal in the same way, it's not going to give more insulin, because as far as it's concerned, you didn't need more insulin, you came down on your own. Or if you announce a fake meal, you know, one, do another meal announcement, even though you're not eating more. Well, we have certain rules about our adaptation, if you announce another meal in that period, that will cancel the adaptation because we can't tell which insulin we're going to give as ascribe to that first announcement or the second announcement. And so we just decide, okay, we're not going to learn from that announcement. You know, we're conservative about which meals we use for learning. And that's fine. As you're using the device over a long period of time, you don't have to adapt on every single meal. But if you consistently are using extra insulin, either by telling, you know giving insulin, the eyelet doesn't know about or doing additional announcements, you will completely block its ability to learn that it needs more insulin the next time,

Scott Benner 28:26
how long do I need to be on the device before I don't expect it to struggle?

Steven Russell, M.D. 28:31
Well, it varies a little bit from person to person, it depends on how high your total daily insulin dose is. But I would say that if you follow the recommendations for allowing the island to learn you, most people have have gotten to a pretty good place in terms of their meal announcements within five to seven days. Okay. Now, what we found in the pivotal trial was that on average, people got to their new time and range within 48 hours. But that doesn't mean that the meal doses it adapted that fast. What was happening is that the islet was relying more on correction, insulin, the correction algorithm. And they they were getting under pretty good glucose control, on average within that 48 hour period. But over time, there was a shift as more insulin was coming in from the meal algorithm and less insulin was being delivered by the corrections algorithm. Okay.

Scott Benner 29:28
So here's my next question. Then. Exercise. I have a message here a question. So this person says or a camp director to T one camp. He says we have many families that are on I let the they're debating on sending their kids to camp due to concerns that there's no way to reduce basil for demands of camp. These people are citing to him that they are having issues around activity with no way of announcing activity or reducing Basal. So what do you think about that?

Steven Russell, M.D. 29:56
My recommendation to kids go into camp is to think about how much their activity is actually going to change a camp. Because some kids are much more active at Camp than they are at home, and others are not. So if they're not going to be more active, it's, it's probably not going to be a different issue than whatever they've been addressing at home. If they are dramatically increasing their activity, then one of the things they could potentially do is raise the glucose target. That's a lever that to that we've haven't really talked about to date, or at this point in the in the discussion, but there is the possibility of changing the glucose target. I would say that, you know, exercise is a whole conversation. Yeah, and right now, we don't have an exercise mode for the eyelet. What we recommend is that people, for the most part, keep the eyelet on. And most kinds of exercise actually don't cause the blood glucose to drop, you know, weightlifting, high intensity, interval training, and so forth typically don't cause a drop in blood glucose. And so it makes sense to leave the eyelet on and running. For exercises that do cause the blood glucose consistently to drop, the recommendation is to do one of two things, either leave it on, you'll, it'll see your blood glucose drop, and it'll suspend insulin. And you may still need to take some carbs to cover that period, until the insulin levels of the insulin on board decreases. And that takes some time because it takes, you know, on average, five or six hours for insulin to really clear. And so you should definitely have some carbs available. And then take whatever amount of carbs is needed to keep you from going low, although try not to over treat below, so that you're not provoking the islet to give more insulin, or you can just disconnect from the eyelid. And that way, the insulin levels will obviously be much less, much lower. And if you disconnect from the eyelet, then you have the option to take some carbs to raise your blood glucose. Okay, going into the exercise, just like any other AI D system, it's really important not to re carb load for exercise without disconnecting from the island. Because then what you'll do is you'll cause your blood glucose to go up the Island will see that and respond to it with additional insulin dosing. And so then you're going into exercise with even more insulin on board. We are aware that there is I think, a need for an exercise mode for the island. And we have designed one, and we're working on the strategy for for getting it out there, we have to talk to the FDA about you know what, what the appropriate way is to get that update out. And once we have clearance for that it will come out just like any of our other over the air updates. Okay, is that,

Scott Benner 32:51
uh, you hope for this year or you can't even say inside of a calendar year?

Steven Russell, M.D. 32:58
I think that I better not have any chances of getting it out in a particular timeframe. I certainly hope for it this year.

Scott Benner 33:06
Okay. You're working on it. Now. You hoped for it this year. Okay. Well, that maybe doesn't answer that question. Hey, you talked about targets. What do you mean that you haven't been telling people that there's targets? What does that? Well, we hadn't talked about it in conversation, one of the targets that I can set with eyelid.

Steven Russell, M.D. 33:20
So there are three levels of target, there's the usual target, the lower and the higher target. We intentionally don't talk about the what glucose level those are right up front, because we're trying to simplify it and to allow people to manage their diabetes without thinking about numbers. But everyone wants to know what they are. And they are on 120 is the target for usual 110 is lower, and 130 is higher, I just want to make the point that they aren't directly comparable to targets with other systems, because the algorithms work differently. So Ed likes to joke that if somebody asks what the target says, he's like, Well, what is the gear ratio in your car, what matters is not actually what the target is, but what kind of average glucose you can achieve with it. And what we found in the pivotal trial was that about 60% of the time was spent with the usual target 20% with the lower 20% with the higher. And with that mix of targets, we had an average glucose of about 155 and adults. So you know, right at an average a one C of 7%. But of course, the target for a particular person is what's appropriate for that person, right. And I should also point out that there you can have two different targets a day so you can have one target during the daytime and one target at night. And you can choose the timing of the start of that daytime target and shifting back to the nighttime target they can be at any time. So that's something that we think people shouldn't just do on their own, they should talk to their healthcare provider about but it's not uncommon to have two different targets one during the day and one at night, can they be automated? Yeah, they are. So once you set the pattern, it's just a recurring pattern happens. Okay. So, you know, probably the most common target is just to be at the usual target the whole time. But probably the most common after that is to have a target, that's one step lower during the daytime when people are eating, and a step higher than that at nighttime when they're not. And that means the eyelid can be a little bit more aggressive at dosing, any postprandial any after eating rise in the blood glucose, okay. And it just tends to make it more efficient at managing any hyperglycemia during the day for some people.

Scott Benner 35:51
My next question is from a woman who says that her husband has a co worker, a friend who's using ILF, that the guy's a snacker. And the pump doesn't seem to be handling that well. So what should I do, if I'm the kind of person who walks through the room and grabs seven carbs of something and throws it in my mouth, what we

Steven Russell, M.D. 36:07
recommend is that people announce carbs that they're eating, snacks that they're eating, if they have as many carbs as a meal. So the usual for me meal is one, a half a less meal is half of that. And a more is one and a half times that. So those are sort of the levels of what we call a usual for me a more and less meal. So if a snack has as many carbs as a less meal, so it has as many carbs as half of your normal breakfast or half of your normal lunch, or anywhere down to a quarter. So that that range is like a quarter to three quarters, that's a last meal. If it's anywhere in that range, they should go ahead and announce it. We say if it's less than a quarter of a usual meal, they shouldn't announce it. And they should just let the correction algorithm manage it. But if it's in this case, if if they're finding that they're having hyperglycemia, after not announcing those snacks, my guest is that they have significant carbs in them. And they probably should be announcing them as meals. So

Scott Benner 37:15
you're thinking already about the activity addition? Do you think about like a grazing mode? Or like you don't? I mean, there's, I mean, it'd be Listen, you've been an endo for a long time, right? So Thanksgiving comes, I tell people all the time, like put your basil up 20% Like you don't you mean, like you're gonna be eating throughout the day? Like, let's lay a heavier, you know, blanket of insulin over the situation? Like, is there thoughts about like, I guess my, my real question should be, as you're seeing it in people's hands. Are you thinking like, oh, this would be good to add? Like, are you having those thoughts, we

Steven Russell, M.D. 37:50
actually have designed a snack announcement that will be even less insulin than a less meal. There'll be a kind of a different category. I would say that for most snacks. If they're gonna if they're causing a significant rise in blood glucose, it's a meal, they probably should have been announced as immediate. Right, right.

Scott Benner 38:10
But I'm talking about like, the real like, you know, like, I don't know, a candy bowl and you grab seven gummy bears, and it's, you know, it's eight carbs or nine carbs, something like that. And like, you have no ability to maybe the biggest, like sticking point right now. And I am I'm certainly not leaning into it. I am not a person who says I don't want to change, right. So I don't get upset when Facebook changes the way it looks. You know, if a car company puts out a card, it's not quite done yet. I'm like, Oh, this is what they need to do to get to it. Like I'm okay with it, like, so I'm flexible about that stuff, and about diabetes as well. So my question, I guess is, how do people who are just so accustomed to doing something one way? Do you think if they just tried it? Eventually they they'd be like, Alright, I'm good with this? Or do you think that there's going to be a happy medium in there? So you're looking for a snack button, you're thinking about exercise? I mean, I love the idea of eyelet. Like, it's it's a romantic idea about taking good care of yourself with less input. But what does that mean? I guess, like, I'm going on a little bit, but if you told me my daughter's blood sugar was going to be 155. I'd say oh, God, what did we mess up? Right? So like, I'd be looking at like, is the basil wrong? Do we have the insulin to carb ratio wrong? Like there's part of me that feels like we're having this initial conversation with beta bionics, who is now looking at how to go to a by hormonal pump. And I'm thinking like, I'm going to look back on this one day and just see this as the infancy of the pump is is that maybe how I should be thinking about that?

Steven Russell, M.D. 39:46
Well, let me say that I think we we really see tremendous value in by her model. And the reason is, I like to think about it in terms of a population health reason with the island we can get About 50% of people to have an agency less than 7%, most of the remainder to have anyone see less than seven and a half with the buyer hormonal, we expect to be able to get 90% of people to have an agency less than seven, and 100% to have an agency less than seven and a half. That's what our pre pivotal data says. So it's it's lowering the average glucose, if you will, by about another 15 MCs per deciliter or about another half percent of a one C, you know, why do I keep talking about seven and seven and a half, obviously, seven is the recommended a one C target that ADA has come out with, and that's based on the diabetes control and complication trial, it's worth pointing out that the diabetes control and complication trial started with people who had an average valency of nine. And what they found is that if they got their control group that had and I want to point this out, on average, a one C of 7%, not everyone got lower than that, the intensive control group had an average a one C of 7%, they found that that was sufficient to cut the the progression of complications or the development of new complications to the background level. So if you look at that hockey shaped curve of complications versus a one C, below seven, there is no signal for further progression of complications. Since that time, there has been some data like registry studies from the Scandinavian countries that, you know, look at people who have been in there, who everyone who gets diabetes is immediately tracked. It's like a registry studies the whole country. When they go back and look at that, they find that people who had an A one C below seven and a half from shortly after the time they were diagnosed throughout their entire lives never get complications of diabetes. And one more piece of information is people who have what's called Glucokinase Modi, it's a particular single gene mutation. That means that people have a average glucose from birth in the 160 to 170 range. They're born, their their pancreas works, it just works for a higher setpoint. So there's several 1000 of these people in the world. They've been carefully studied, followed throughout their lifespans, they don't get any complications of diabetes. So I think that probably if we were able to get everyone below and a once you have seven and a half, diabetes, complications wouldn't be a thing.

Scott Benner 42:29
You bring up something that I never know how I've been doing this a long time. And one of the questions that people asked me that I just don't know how to answer is what is the benefit of being lower? And I don't know, I have, I always say I have no idea. Like, I don't know, when it always comes down to if you can, without it being too much trouble. I'd err on the side of doing it. I can't tell you. And I mean, those are interesting studies for certain. I think the problem ends up being and this is obviously more philosophical than anything else is that if it happens for a person, they live their whole life with a seven, for example, and then they have a problem. You can't go backwards and try again. Like, right, so there's the that's the rub. And I also feel like if we were alone in a bar, and I asked you, if you were working on the algorithm having a lower target, you would be like, oh, yeah, of course, Scott, we're on that, don't worry. I'm just super interested in where this is all going. I love the form factor. I love how it wants to work. And I appreciate you sharing that information, because that's the closest I've ever come to an answer to that question like, what's the what's the benefit of lower?

Steven Russell, M.D. 43:36
I would argue that there isn't, there isn't evidence that there's a benefit for lower. So what do I tell people? I tell people that if you can achieve a lower ANC without hyperglycemia, then great, and you want to then great, then fine. But if there's a significant trade off in terms of increasing hypoglycemia, it's not worth it. No, I don't I hate to either. And I would never target below, say 6.5. I mean, there's, you know, you just can't make an argument and evidence based argument for for shooting for an A one C lower than that in my mind. Well,

Scott Benner 44:09
you're also not trying to sell a pump to somebody who's walking around with a five, five a one C to begin with, by the way, none of these algorithms without some real like, intervention, tinkering, like deeper understanding. Like you're not you're not getting there unless you unless you really know that hey, yeah, that makes me wonder, how does the algorithm work for people who are very low carb works

Steven Russell, M.D. 44:30
great. I mean, that's, that's an easy case. Okay. Those people tend to do well, no matter what they do. So the algorithm works really well in that context. Okay. I kind of want to go back to that issue of, you know, what's the advantage of going lower? And, you know, as I said, I think that there isn't much evidence that there is an advantage in going lower and if we go to the sitting in a bar scenario, the reason that I give for wanting to use The by hormonal system is that we can just get more people, in this case, everyone to have that a one C that I think will pretty much eliminate complications, it's not about taking somebody who already has an A once fee of 6.5 and bringing them down to six, I do you think that for individual people, because we can be a little bit more aggressive with the algorithm, it probably will give them the capability of lowering their agency by another half percent, whether they should is a separate issue. I would at that point, if if somebody you know, has an agency of six and a half, the way I would use glucagon is not to further lower their agency, but to further lower their hyperglycemia. Okay, that's where the, that's where the benefit comes from my perspective perspective. And also, it has the additional advantage of meaning that you don't have to take oral carbohydrates, with all these insulin only systems, they're all pretty good at suspending insulin, if it looks like the person is going to go low. But they all occasionally fail in that, that you still need to take carbs to treat a low. And, you know, it's frustrating to people to be, you know, doing exercise because they're trying to, you know, trim down or something, and then they wind up having to take a bunch of carbs, to treat a low that happens when they exercise. So the glucagon has an advantage from that standpoint, and it also just the spontaneity standpoint, you know, not having to take carbs, just seeing your blood glucose going low, and then just going right back up without you doing anything, that certainly increases peace of mind. And, you know, whereas with the insulin only system, we found that we were able to lower that agency by half a percent, on average, more for people who are higher, obviously, we didn't lower it for people who already had agencies below seven, and we didn't increase hyperglycemia. With the bio hormonal system, we're able to lower it even further. And actually also reduce hyperglycemia.

Scott Benner 46:58
You're, you're testing it now.

Steven Russell, M.D. 47:01
We are not testing it again. Yet. We just recently announced an agreement with Cirrus pharmaceuticals, to test a new formulation of stable glucagon. And we're moving forward with that with all haste, because we really do think that that by hormonal system is going to provide terrific advantages.

Scott Benner 47:24
People are listening right now if you go back a week in the podcast, you'll see an episode with zeros and eyelet talking about that agreement that they that that Dr. Russell, just, yeah, I've done an interview about that yet that's gonna go up right before your stuff. I'm excited by it. Like, I have to tell you, I believe my daughter's 20. Right. For the most part, my daughter is away at college right now using IEP s. And a she's got an A one C like six one, I think and that's at college like and not just the college like you're thinking of it, my daughter is not like a crazy party person, she's working incredibly hard, like seven days a week doesn't take off long quarters that go into six months, times when she's at school, and that she's managing that is insane. It's absolutely fantastic. But we also do a really good job of her not having lows. Having said that, I've seen really emergent lows. And I've I've watched her have a seizure when she was two years old, she had one when she was a high school senior, it was both times variables that were not common everyday stuff. I just think in my heart if her pump would have noticed that and given her some glucagon, it might have been maybe the greatest thing that I've ever seen in my life. Like, seriously, I don't know how people who are using insulin are not Ultra aware of this constantly. To take that brain worm out of the back of my head would be amazing. You know what I mean? So I'm with you, I that. This is probably an unfair question. But if you ever talked about would you license this to other pump companies if they were interested? Or are you guys gonna keep glucagon, your your, your algorithm and everything? Like it's some point? I keep thinking at some point one of these systems is going to show and everyone's gonna say, Well, yeah, that's how we should be doing it. And then what are we doing? Then we're in what a retail game. Like, that's ridiculous, right? Like, at what point? Do we just say, because listen, I have my questions here for you 50 people, this is nice. We'll never be tubeless. So like, you know what I mean, there are people who they don't care if it comes with a free pack of bubble gum. You don't I mean, in a bus pass, if it's not tubeless they don't want to hear about it. Like that was my wonderment like, you know what I mean? Like, I wonder if it'll ever it will really get into that interoperability that we all kind of got teased about with tide pool. It doesn't seem like it's ever gonna happen, I guess is what? Yeah,

Steven Russell, M.D. 49:52
we're certainly aware that people are interested in the tubeless form factor. All I'm gonna say about that right now, but okay. where you're we're certainly aware of that. And we realize that that's really important for some folks. So all right,

Scott Benner 50:07
I take your point, don't worry, I can read between the lines. I'm good.

Steven Russell, M.D. 50:12
As far as as far as licensing the algorithm, I mean, you know, Ed, would, it would be a better person to talk to you about this. But we definitely, were interested in making the algorithm available to other pump companies. And there were no takers. That's why beta bionics got started, you know, the, the idea of having a system that's this automated was something that I think was scary to other pump manufacturers, and they preferred a system that still left more of the responsibility in the hands of the user, I say, so that if something went wrong, they could say, well, you know, we were not responsible on

Scott Benner 50:52
the pods gotten away from that they're basically telling you now, we don't even want you to understand how it's working. You know what I mean? Like, it's, you know, it's going to do what it's going to do and let it do it. And I mean, you're saying that to you are saying, like, let the thing work, right, like don't? Well,

Steven Russell, M.D. 51:05
I think that's that it's different, I would argue, because we're very clear, we have a lot of information about how our algorithm works. And I think that's a little different than than Omni pod. But Omni pod also still requires the user to do a lot. What I've learned clinically with the Omni pod is that if you want to get good glucose control with that system, you need to make sure that you fully dose your your meal, your your meal, carbs, sure, because it's a fairly conservative algorithm in terms of giving corrections and adjusting basil, and so forth. So you can get good glucose control with that, but you need to be pretty aggressive about giving the full amount of insulin for carbs, and also giving manual correction bonuses to get the best glycemic control. So it's still quite dependent on the expertise of the user in being able to count carbs accurately, and to choose the appropriate times to give corrections and you know, to to give the corrections that are needed and not give the rage boluses. So it still is quite dependent on the user, whereas the eyelet is not with the island, it's really more about not doing certain things that can confuse the island. And and, you know, sort of teach it the wrong things, right. It's often about doing less with the island, not more than and in that sense. It's really unique. Every other diabetes control system, the more you interact with it, the more you pitch in, the better glycemic control you're gonna get. And the island is unique. And that's not the case. What's

Scott Benner 52:37
our average excursion, I expect with an eyelet? Like, what number am I going to see a spike go to, for example?

Steven Russell, M.D. 52:47
Well, if you have a meal and you and you do announce that meal and your meal doses have adapted, it might be quite small, might be 150. But it might also get to 200 are transiently above 200. It just depends on where you are in that in that range of what your usual for me meal is for instance, how much of the insulin actually came up front and how much is coming as correction Bolus. I see. I

Scott Benner 53:14
mean, it's all like relative like I when I tell people my daughters they want to see I think they imagine like an ad three blood sugar that goes on for weeks and months, but she has spikes at meals just like everybody else.

Steven Russell, M.D. 53:25
And soda. Why, by the way? Yeah, I don't have diabetes. Yeah, but I wear CGM. And my blood glucose goes above 200. Sometimes no kidding. Absolutely. And yeah, I mean, that's not uncommon for people without diabetes. And I think we're only now appreciating it because you can wear CGM and you can see that which you normally wouldn't have seen right. Now mine automatically comes back down and I don't have to do anything about it. But it's not uncommon for it to go above 200

Scott Benner 53:53
Can I ask how old you're 5066 Okay, I'm 52 I have to wearing a CGM. I have to eat intentionally to get my blood sugar to go over like 160 But I'm talking about like pizza on top of fast acting sugar that's like it's I had to like gorge myself to make it happen. So it's interesting. Look at give me I'm showing off. Steve varies

Steven Russell, M.D. 54:15
varies from person to person to person to person. And I think you know, breakfast is the meal if I eat a high carb breakfast, I'm definitely going high. Okay, because it's you know, and it changed the way I ate you know, I would in the morning would have you know, some waffles and some peanut butter and maple syrup. And when I saw what that did to my blood glucose, all of a sudden I started eating more eggs.

Scott Benner 54:39
Everyone who's ever come on here, as Kevin Sayer was on here one time he's like, I wear my own product and just like four things I just stopped eating. Yep. So listen, we talked about like, okay, but even a person without diabetes is going to see an excursion up but there's also truth is there not that a person without diabetes also might see a blood sugar into the 60s throughout the day. So I mean it So it begs the question like, why were you guys not a little more aggressive with it?

Steven Russell, M.D. 55:04
Well, I think it's the idea is to try and tune the system so that we're improving or lowering the average glucose, we're lowering the a one C without increasing hyperglycemia. That was, effectively the way it was tuned over those pre pivotal studies that we did. And that's what we found in our pivotal study, we lowered aid, what CD didn't change the amount of time less than 70 and less than 50 for sort of a pragmatic choice to tune it that way. And of course, that means that, you know, in some people are going to have more hypoglycemia, and some people are going to have less, right. And we're just trying to kind of pick a middle path where we get the best glucose control we can without putting people at risk.

Scott Benner 55:52
Yeah, in fairness to every company. And every algorithm, there's the nebulous part of the conversation that we don't talk about, which is some people just eat differently. And so you're trying to make a thing that you can just handle the world without knowing each person individually. So there has to be buffer, I guess, on either side of it. I guess my more maybe, maybe my, my bigger question is, if the mind if the if the brain trust that is beta bionics now existed on day one. Do you think the algorithm would be more aggressive today? Like, have you learned more now? Or you're still very comfortable with how it's done?

Steven Russell, M.D. 56:25
I don't think it would be different. Okay. I think we might, you know, we're seeing that, we would like to add a, a, an exercise button on the island. And that wasn't built into it from the very beginning. And so now we want to add it. And I think one of the reasons that wasn't built into it from the beginning, is because the island kind of started as a by hormonal system. And we didn't really need it for the bio hormonal system. And then we got to insulin only. And we found that we were still getting very good, sort of surprisingly good results with the insulin only system. And it was quite differentiated, it was getting results similar to what other ad systems were getting, but with a lot less work. And we thought, you know, that is, that is a differentiated thing that we should get out there, even though, it's going to take us a little bit longer to get the buy hormonal product out because of the complexity of doing a drug trial as well. So that's why we chose to move forward with the insulin only system, because it it is a big difference. It I think it does bring a tremendous amount of value. But that's also why we're not stopping on the by hormonal system, because we think there's additional value that we can bring by bringing in that that by hormonal piece. So back

Scott Benner 57:45
in the day, the glucagon wouldn't hold up in the pump, right? That was the biggest.

Steven Russell, M.D. 57:49
That's absolutely right. So we did all of our pre pivotal studies, or most of our pre pivotal studies using the red kit from Lilly, and we would just reconstitute that glucagon. And we had to change it out every day. Because it wouldn't, it wouldn't last longer than that. And shout out to Lily for providing us enormous amounts of that red kit glucagon for free, they were fantastic about that, we would literally get boxes that were three feet on a side full of nothing but those red kits to be able to do our pre pivotal studies. But that wasn't going to be practical in the long run. Yeah. And so that's why we needed a stable glucagon. And fortunately, two came along. And we're, you know, moving forward with with one of those a new formulation of the zeros that the actual zero Asal glucagon that's available right now for rescue treatment. That one won't work in a pump, because it actually damages the plastic. But a different version of it a slightly modified version, it looks like it's going to work just fine and a pump. And so that's what we're going to be moving forward with.

Scott Benner 59:00
Paul was explaining that to me in that recording, because I said, Oh, you're just gonna put g voc into the pump. He's like, no, no, we have to do a formulation that changed. And I was like, Oh, that's really interesting. Like, and you know, pretty cool. Honestly, Steven, that an idea? That is how old now? I mean, when when did that study happen with those red kits?

Steven Russell, M.D. 59:20
For you guys? Well, the very first one happened in 2008.

Scott Benner 59:24
Okay, so a lot of years later, like 17, that sounds like to me, you know, you're still on it, which is pretty great. I also want to say this too. I recently just floated out into the world, like if anybody wants to come, I think I said online, if you have a device or a product that helps people with diabetes, and you want to come on the podcast and talk about it, come on, and you and I are having a pretty honest conversation I'd say about, you know, about eyelet. And I appreciate that because not everybody stepped forward and was interested. So thank you. I really do appreciate talking about it like this, because it's fair to say all these algorithms and They can all be better, obviously, right? It doesn't it's not a denigration of what they are now. And if we don't talk about it like this, then where's the onus to do the work? You know what I mean? Like I all these companies should be in a room right now looking at their data thinking, how can I make this better? And if they're not I, I hope, and I hope they'll consider doing it. And it sounds like that's what you guys are doing. So I appreciate it. I

Steven Russell, M.D. 1:00:23
totally agree. I mean, look, AI D is so impactful, it makes a huge difference. CGM was huge. And AI D is huge. And I think that probably everybody with type one should be on an AI D system. I think that beta bionics with the eyelet is trying to be available and reach a group of people that may have a harder time working with some of these other systems that require more sophistication on the part of the user ability to carb count, choosing the right times to do corrections, and so forth. Yeah. And so I think that I talked about democratizing good glucose control, it shouldn't be just for the elites, it shouldn't just be for the small percentage of people who are very numerous and, you know, have the best executive function so they can be on it all the time, and paying attention and, you know, not working two jobs, because, you know, you really with diabetes, it's like a second job. So if you already have two jobs, then you know that your ability to spend the amount of time it takes to get that excellent glucose control is limited. So I think one of the things that we bring is bringing the possibility of good glucose control to people who might not be able to do it with the other devices. And for people who already are able to achieve good glucose control with other devices, it's another option that can reduce the amount of time they have to spend with it. Yeah, not everybody wants that. You know, I think it's important to note, it's not for everybody, that kind of people who are want to be on loop or one of these other systems and are the people who are have control IQ, but they've turned it off. And they've just got it on, you know, sleep mode at all times. Because they, they they feel like they can do a better job. Those are probably not the people for the eyelet. Right. Frankly,

Scott Benner 1:02:14
the button the button pushers in the dial. Turner's might not be your your bread and butter. But there's a listen, I say it all the time. Well, let me go back earlier, when you were describing how the algorithm works, I thought, Oh, my God, that's how I managed manually, right? Like, I think back to like the Pro Tip series in this podcast, which is just me telling you how I got my daughter's a one C down and stable, and how I think about insulin and diabetes. It's all timing and amount. And, you know, understanding the variables like that, that is literally what the algorithm is doing. I didn't realize that till the first time, I saw my daughter on loop, and I could watch through Nightscout. I watched it work. And I thought, Oh, I would have Temp Basal here. Or I would have done this, like you don't even I was like, This is so interesting. It's doing everything for me. And I'm getting asleep. This is insane. You know how happy is about it. But it's never lost on me that even though I watched the podcast help, like, seriously, I'm not trying to, like blow my own horn here. But But this podcast charts in 48 countries around the world, right? Like I wake up to a dozen notes every day from people are like, Oh my God, look at my one say, it's amazing how many people it touches. And yet, if I stopped myself in a quiet moment, I remind myself, I'm probably not touching 5% of people with type one diabetes. Like it just I'm not reaching nearly everyone. This is for the people who have the time to listen to it, that have the acuity to understand it, and have the patience to put it into practice that have the patience to watch it go over and over again until it finally makes sense to them. And then they can kind of do it blindly without even thinking about it. That is not something that's going to work out for everybody. I just know it isn't. And everyone should be thinking about that like, because if not, if not, then what we're doing is we have a bunch of different pump companies who are saying to themselves, there's a block of people with type one diabetes, this percentage of them can figure out how to use this pump will market to them. And then the rest of them just they get left behind. That to me is like I have thought from day one about this algorithm like this is for the people who got left behind. And if you can turn it into something as for everybody, not just for them, then in my opinion, you know, you just jumped ahead. So, you know, everyone else should try to keep up. But you know, I would love to see this on more people and see how it works out. Speaking of it being on more people and seeing things, have you seen it on somebody who's using a GLP yet? I would imagine that's like a low carb vibe. Right?

Steven Russell, M.D. 1:04:46
Right. We have I don't have statistics for you. Sure. And I would say also in our we do post market surveillance all the time. You know, we we can look at the whole population of people on the island and Look at what average glucose they're getting and how much hyperglycemia all that stuff we look at. Unfortunately, we often don't get any information about other medications that they're on. That's not part of the information that we get. But I am aware of people on GLP one agonists with the islet. And as far as the eyelids concerned, that just means that the person is using less insulin. And their glucose excursions are less acute, less sharp, or eased, and they're easier to manage. So and you know, on the island, of course, is continually adapting to the need for insulin. So if somebody starts on a GLP, one, and their insulin needs go down, the islet just adapts to that online. And if they are absorbing food a little bit slower, the meal dose adapts to that. So I don't think there's any reason why you think that it wouldn't play nicely with a GLP one agonist and in the cases I'm aware of, it seems to play just fine with GLP, one agonist,

Scott Benner 1:06:00
I'll say here that my daughter is using Manjaro. At the moment, I I've said it over and over again, but so that, you know, I estimate show you 16,000 fewer units of insulin this year because of it. And it's, it's, and we were doing fine before like, you know, we in fairness, and we're very good at using insulin like so it doesn't matter how high or low carb she has we know how to manage. But this is just like her stability is even more stable. The it gives the algorithm that makes the algorithm look like it's better what it's doing. You don't I mean, like, Yeah, I used to say to people, you know, if you if you came to my house that I have to give one of these things back, I probably fight for the CGM over the pump. But then once they got integrated now I kind of see them as one in the same thing. But I'd have a long, hard think, before you ask me, What can I have back the algorithm or the GLP. I'm doing a small series right now with a guy you might know Tom Blevins. He's an endo in Austin. And Tom and I are recording a small series about GLP I am literally hoping to be one of the voices that pushes JDRF and other big institutions into pushing for coverage and testing, you know, for people with type one diabetes, just based on what I've seen, and what I'm hearing from other people, which has nothing to do with our conversation. But anyway, sure,

Steven Russell, M.D. 1:07:21
I will say that, you know, this is entirely separate from my role of antibiotics, but I'm still a practicing endocrinologist. And I personally use GLP one agonists in people with type one diabetes, who also have the physiology of type two diabetes, and there's plenty of those people, right? There's nothing about having an autoimmune attack on your pancreas, or B or beta cells that modifies those genetic risk factors for Type two diabetes. So as far as I'm concerned, you can have both types of physiology. And for those people, absolutely GLP. One agonists makes sense, I think, perhaps more controversial is the idea of using even people with type one diabetes who are lean, not insulin resistant. And I think that's where, you know, the companies just chose not to pursue an indication for it. But clearly, it does reduce the amount of insulin use and it and it does tend to appetite. Yeah, and appetite and it smooths out the glucose excursions. So it does make a lot of sense that, that it just makes diabetes easier to manage,

Scott Benner 1:08:33
I have to thank you, because you just put that I've been trying to make that point. I keep fumbling with it. Every time I tried to make it. The idea like they used to hear people say like, my doctor says, I have type one and type two diabetes, then people would say that and you'd like you can't have both and it would kind of like, you know, people get upset. But my daughter, for example, like very clearly has PCOS symptoms, which is just the thing you really can't even get diagnosed, you know, weight gain, acne, high need for insulin no matter what she's eating or not. And she didn't, you know, she wasn't overly you shouldn't gained a ton of weight. But she was also 20. Still, whereas I know a person who doesn't have type one diabetes is a young girl in her mid 20s, who has PCOS. And is a clean eater who exercises daily who gains weight every week, just can't stop, right? And goes on a on weego V, and boom, it all just ends and the weight starts coming off and everything goes back to normal. It's absolutely amazing. But the what you're starting to see right now and you probably know this because it sounds like you're doing it is you're you're having to diagnose your patients as having insulin resistance and type one diabetes to get around the quagmire that is the insurance at the moment on this. But I just I really, Dr. Blevins believes that if you don't go out there and do the studies that it's going to be very difficult to push through insurance and it it's going to take a big voice to push the studies along. So Oh, I'm trying to magnify that if I can, just like I'm trying to do with you and anybody else like I listen, there's part of me, Steven. Yeah. I don't want everybody fighting. And I take ads from a pump company. Like, I have no trouble saying that. But I don't want anybody get uncomfortable. Like, I make a podcast and you know, people pay me for ads, but I got a kid with diabetes. I need you guys all out there hustling? You know what I mean? You know, for anybody, you might be listening, thinking, God, I can't believe Scott had this these people on when you know, Omni pod buys ads from him. I want Omnipod to work hard. And I want you all to work hard. You know what I mean? So I mean, absolutely.

Steven Russell, M.D. 1:10:35
I think it's incumbent on all of us to continue innovating. And I'm, I'm thankful that we have multiple different AI D Systems, because I think they're not all perfect for everybody. And I think everyone should be on an AI D system. And it should be one that fits their lifestyle and their predilections and their interests and, and it works for them. And so I think there's no way that any one system is going to be all things to all people. So I think it's great that there are choices. I agree.

Scott Benner 1:11:06
I also think that when you're being diagnosed, the next thing you thought you should have is, what's that you're putting on my arm? Is that a CGM? What is that, but you shouldn't leave the hospital without a CGM. If you had a heart issue, they would put a monitor on you. They would not let you out of the hospital without it. But

Steven Russell, M.D. 1:11:22
yeah, 100% agree. Yeah. And I, you know, one of the things I do is I still work in the hospital. On the weekends, we have this inpatient diabetes service. And it's getting pretty big. Now it takes three doctors to cover it every weekend, we see all these patients in the hospital. And, you know, we're seeing the patients who are already on our service with consults to us. But we also get new onset people in, you know, people get new onset type one diabetes all the time as adults. So I see these folks. And I really try and take it upon myself to try and get them on CGM as soon as possible, you know, send the script down to our pharmacy, and get them on a Dexcom or an Abbott sensor before they leave the hospital. And put in a statement of medical necessity for an AI D system if they're willing to consider it. Yep, as soon as possible. I'm really grateful that there, there are more than one systems out there that are automating glucose control. I really like to get people on CGM as soon as possible after they're diagnosed. And, you know, there's adults getting diagnosed all the time. And, and I really want everybody to think about an AI D system. On the day they're diagnosed when I see them in the hospital. Yeah,

Scott Benner 1:12:42
I completely agree. And I like again, not only is it good for people to have choice, but from a different perspective, it is very good if the space is not controlled by one company, we've seen in the past that company gets comfortable, and then nobody gets served. So that's

Steven Russell, M.D. 1:13:01
absolutely true. And I and I think it's really, it's really important for us to continue innovating. You know, once you have something that's approved in a very highly regulated industry like this, there is the tendency to feel like well, we, you know, it would be too costly, too time consuming. To continue to innovate, let's just keep pushing the product that we already have. But I don't think any of us should be satisfied with that. We should always be looking to how we can make it better.

Scott Benner 1:13:28
Yeah, listen, I have a two year outboard for podcast, they should be doing the same thing. As soon as everybody I always say you get your thing through the FDA, everybody gets a vacation, then we come back. And we started thinking about how do we push this farther. And if you're not doing that, then I think shame on you a little bit. So seriously, like, it's just, I mean, you saw it in the past, one company had control of everything. And they were just like, whoo, and now look at them rushing around trying to get back in the game, you know what I mean? So it

Steven Russell, M.D. 1:13:55
can, it can be that kind of behavior winds up coming back to burn you in the end, but it tends to be years later in their case. I think now that there's more people in the game, it's doesn't take as long right? For that kind of behavior to loop back and burn. It's

Scott Benner 1:14:14
not just cyclical now because it's cyclically happening, like four or five different in four or five different buildings. And that really is valuable for us because listen, if you're gonna talk about the business of it, we got the big thing through now we're going to make the money I'll cut costs right now I'll be a big hero bringing a nice bonus for myself, I'll retire and then the problem will be on somebody else when we're not innovating anymore. That's the backside business problem. So I guess what I'm saying is if you're in a business where that's happening, you better speak up or 10 years from now your job is going to be worth much anyway there. I just want to make sure everybody's working Steven, that's all I got. I got a I got a daughter I got to worry about you know, well you know,

Steven Russell, M.D. 1:14:49
we are we are working very hard on it and and as you as you know, you know, we launched the product with G six and shortly after We put out an update that made us compatible with g7. And, you know, we've been very clear that we want to be compatible with any CGM that is able to meet the ice CGM stand there. It's because we think people should have choices. And we're going to continue to innovate in other ways as well. Cool.

Scott Benner 1:15:19
It sounds like maybe you've reached out to the people ever since then, perhaps they just got their IEP s. Distinction, didn't they? They did. Or I used the wrong terminology. I CGM. Excuse me, but yeah, CGM.

Steven Russell, M.D. 1:15:34
Yeah, yeah. And I actually a fan of that technology. I, one of the things I do in clinic is to replace and replace those Eversense sensors. And I think it's a it's a good system.

Scott Benner 1:15:46
That's excellent. Good. Well, hopefully, I mean, I, they buy ads from me too, like, just so I'm being clear. But I always say to them, like, you know, like how the transmitter vibrates as like, Wouldn't it be cool if the pill vibrated? And they're like, Wouldn't it be? And I was like, it would be wouldn't it be? Like somebody work on that? That's a great, I mean, can you imagine that an implantable CGM that gave you a little shake if you were low or too little shakes? If you're getting high? That's insane. I mean, I think it'd be fantastic. Anyway. Is there anything I didn't ask you that I should have something we left out?

Steven Russell, M.D. 1:16:18
Hmm, let me think I know there was some because I had some things on our because I have here.

Scott Benner 1:16:25
Can you tell me about the you

Steven Russell, M.D. 1:16:27
know what, there was one that was on there? What are the best practices in the first two weeks? I'd love to address that, please. All right. Well, one of the questions that comes up is what to do when you first start on the island, what are the best practices to get the most out of it. And those best practices really are derived from the way the algorithm works, what you want to do is give the algorithm the best chance to learn you as quickly as possible. And because the way the meal algorithm works is it looks at the the four hours after the meal, we do ask people to space out their meals by four hours, initially to allow the islet the chance to learn how much insulin they need for the meal, because we have these rules that if you get another meal announced within that four hours, it will cancel the adaptation, okay, now there is an exception to that, which is if you announced multiple meals in the first hour, it will actually combine those meals and adapt on the sum of those meals. And that's quite useful for announcing meals by courses. So you go out to eat for dinner, and you have an appetizer. And that appetizer has sent you out to eat maybe as many carbs as your usual meal. So you announced the appetizer, and now your main course comes out. And that may have more carbs than your usual meal. So you announced that and maybe you then have dessert, you want to announce that it will combine all those announcements and adapt on the some of them. And that may be better than trying to anticipate at the very beginning of the meal, how much total carbs, you're going to have for the entire period, for two reasons. One, because it may be hard to do you not sure whether you're going to have that dessert or not at that point. But to because if you took all of the insulin, if you told the islet, you're going to have all those carbs right at the beginning, it might give too much insulin too early. In other words, you know, an hour later, when you actually have the dessert, you want to have that insulin, then not at the very beginning, it might be too much too soon. But after that first hour period, if you announce another meal in that two to four hour period, it'll cancel that adaptation. So if you never space out the meals by four hours, it's never going to have a chance to learn after that initial learning, then you can be much less regimented about it. You know, if you decide to have a snack a couple hours after the meal, have at it, go ahead and announce it. That'll cancel the adaptation for that meal. But so let you know there you have lots of opportunities to sort of update the meal announcements, and most people tend to eat about the same amount, you know, same stuff anyway, right. And so you probably don't need to update it. But in that first week or so, spacing them out is good. Also, eating meals that really are typical for you or usual for you is good so that it has a chance to learn that there is always this temptation that you've got a new system, like a new fancy car and like let's try this thing out, see how it goes. And we definitely see some of that. Yeah, I remember in one of our first outpatient study, a long time ago now, we this was early on when Twitter was new and shiny. And one of our users had a Twitter account and he was tweeting all of his meals that he was having. And you know one of them was a plate with a burger fries, a couple beers and then stack of of little dessert dishes hmm And, and he's like, you know, I just had this meal. And, you know, seven bowls of ice cream hashtag bionic pancreas?

Scott Benner 1:20:09
Can I tell you how old I am? I know that photo. Yeah, I can't believe. I just thought have I been doing this that long? I know exactly what you're talking about. That's crazy. Yeah, yeah. So what's the downside isn't doing that?

Steven Russell, M.D. 1:20:25
Well, the downside, of course, is that the chances of being able to adapt on that meal are not very good. And certainly it's not a usual meal. least not for most mortals. Yeah. So really, if you want the eyelet, to learn you, you've got to, you've got to give it the right information. And this is when we see problems. These are the kinds of problems we see somebody, like, let's say they, they, they have habits that they've developed over the course of a long time with diabetes. That totally makes sense with some other systems, but don't make sense with the eyelet. But they find it hard to readjust. So I'll give you an example. Somebody has that first meal with the eyelet. And their blood glucose goes high. And that's a common occurrence, because it's starting off with this very low dose, they see that go high. And they think, Oh, this thing isn't going to give me enough insulin. And so the next time they announced a meal, they announced it as a more meal instead of a usual meal, even though they're eating a usual meal, right. If they just announced it as a usual meal, it would have given them more insulin, because it learned from the last time, okay, but now it doesn't have a time, it doesn't have a chance to show them that. And they will get a little bit more insulin that one time because, of course, they announced it as a more than usual. But that will actually make it think that they need less insulin for a usual meal. So it has the exact opposite effect over time that they intend. So it works wants to get more insulin, but in the long run, they'll actually get less. Yeah. So the islet, because it's adaptive, it has this unique characteristic that you can, you can't trick it, but you can confuse it. And if you tell it things that aren't true, it will learn the wrong thing, right. And another example that is totally understandable, given you know, how people have been managing their diabetes is they're about to eat a usual meal, but they're like, but my blood glucose is dropping. So I'm going to announce it as a lesson meal instead of a usual meal, so I'll get less insulin. The problem with that is that the islet is already taking into account that dropping glucose in terms of its Basal dosing, it's correction. It's like, if you're in a self driving car, and it's turning around the corner, but you grab the wheel and turn it to, and now you at the curb, you're both trying to take care of the same thing. And you're overdoing it, I've

Scott Benner 1:22:46
come to believe that we've reached the level in some technology, you can outsmart it, you can't even understand what it's thinking about. And you know, your little thoughts are gonna get in the way I learned that with loop when my daughter started using a loop. Like if this isn't working, our settings are wrong. Our timing is wrong. Me trying to fix a problem is just going to make it more confused. And it wasn't like a learning stitch. Yeah, I'm going to try to hack through. Plus, why am I putting myself in that situation where I'm constantly having to do more, when it should be automated as much as it possibly can be? Yeah, no, I mean, it's, it's it's AI, right? Like, it's it's a it's a learning model. It's considering just more things than, you know, exists, let alone that you could consider and and it's on different timelines, which is That's right. Yeah, yeah, all

Steven Russell, M.D. 1:23:37
that adaptation is going on. And if you try to outsmart it to hack it, it'll just screw up the adaptation, things will get worse, not better. But that is a really hard thing, especially for the knob, Turner's button pushers, folks, it's just so hard to sit on their hands and and wait for the system to learn. And so we, you know, some of those people do want to try the eyelet. And we're encouraging of that, if they want to, as long as they're, you know, willing to at least try re considering how they manage things. And some of them find that they can push through, they can sit on their hands for long enough for it to learn and do well. And then they think, Oh, great, I, I'm fine with not doing all that extra work as long as the results are good. Yeah. Interestingly, we've also seen some folks who got undeniably great results on the eyelet in some cases better than the results that they were getting with all of their work. And they just still find it an uncomfortable thing. They want to be able to go in and give that insulin, even if they're not going to achieve a better result. That's just who they see themselves as being Yeah, and that's fine. That's fine.

Scott Benner 1:24:52
It's interesting. It is it's the psychological. We I've had these existential conversations with type ones before about Like, what would you do you know if diabetes disappeared, and the number of people who say that they wouldn't even want that to happen, because they don't know who they are without diabetes is fascinating. Like, you know what I mean? Like, it really is interesting how much it becomes a part of, of who you are and what you do every day. Anyway, and there's

Steven Russell, M.D. 1:25:17
just sort of a pride of being able to manage it, like you're really good at this, this is something that I have got down. And so taking it away feels like a loss almost. Yeah,

Scott Benner 1:25:27
I did all this work to understand this thing. I let it go. I have to tell you, it's even between you and I, I don't want to sound pompous. But I can manage insulin within an inch of its life. I'm really good at it. I kept my daughter's a one C like 5355. No problem through like middle school, high school, no big deal. And then I was like, oh, god, she's going to go to college. And you know, like, she's not going to do the stuff I do. But luckily, prior to that, we started to use a loop before Omnipod five was even available. And I got to sleep. And once I got to sleep, I thought, Oh, I was gonna die. I didn't even know it. You know, like, like, I was my my No kidding, that by the time I got my daughter off to college, like I had to go to a doctor and say, Okay, now we gotta save me. Like, you know what I mean? Like my health had gotten poor. Just it's not sustainable. It just really Yeah. So

Steven Russell, M.D. 1:26:20
that's right. I mean, that's very impressive. And I'm always impressed by people who can do that. And there are plenty of people out there who can do it, but there is a cost to it, there is a real cost to it. It just takes years off your life. You know, I

Scott Benner 1:26:33
was not going to make it the whole way. Like I just if I had to do that for another 10 years, I have had times in my life where I've sat in bed in the middle of the night, and my brain is vibrating because I hadn't slept. And I've actually had the conscious thought, I'm going to have a heart attack. Like I'm gonna die like I have to go to sleep. And then you look at that blood sugar and you go I can't right now because we made a correction and like Boba, like that whole thing. All that is gone. Like I just, and I'm telling you, if you add glucagon to that, I might, I might, man, I might sleep with a noise machine. Like I might be like, I really don't want to hear a damn thing. Well, this is let me sleep. Anyway. Good luck to you. Godspeed. Seriously, I hope it goes exactly the way you guys are envisioning.

Steven Russell, M.D. 1:27:18
All right. Thanks a real pleasure talking to you. Oh, sincerely thank you for thank you for taking the time to have me on now. It's a pleasure.

Scott Benner 1:27:24
Hold on one second for me.

A huge thank you to one of today's sponsors, G voc glucagon. Find out more about Chivo Capo pen at G Vogue glucagon.com Ford slash juicebox. you spell that GVOKEGL You see ag o n.com. Forward slash juicebox. A huge thanks to us Matt for sponsoring this episode of The Juicebox Podcast. Don't forget us med.com/juice box. This is where we get our diabetes supplies from you can as well use the link or call 888-721-1514 Use the link or call the number get your free benefits check so that you can start getting your diabetes supplies the way we do from us med Jalen is an incredible example of what's so many experience living with diabetes. You show up for yourself and others every day, never letting diabetes to find you. And that is what the Medtronic champion community is all about. Each of us is strong and together we're even stronger. To hear more stories from the Medtronic champion community where to share your own story visit Medtronic diabetes.com/juicebox And look out online for the hashtag Medtronic champion. If you're not already subscribed or following in your favorite audio app, please take the time now to do that. It really helps the show and get those automatic downloads set up so you never miss an episode. Thank you so much for listening. I'll be back very soon with another episode of The Juicebox Podcast. The episode you just heard was professionally edited by wrong way recording. Wrong way recording.com

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