Latest / BioSpace / The next era of diabetes management
Transcript
- BioSpace: My name is Jennifer Smith-Parker, Director of Insights at Biospace, and you're listening to Denatured. In this episode, I'm joined by Dr. Sarah Howell, CEO at AeroCore Therapeutics, and Dr. Wendy Esleen, Clinical Endocrinologist and Director of Clinical Research at the Mountain Diabetes and Endocrine Center in Asheville, North Carolina. We discuss how the diabetes landscape is improving, but treatment still needs to become simpler and easier for patients to use every day. Hey, Sarah and hi, Wendy. Thank you so much for joining this episode of Denatured. If you could please introduce yourselves, that would be great. So I'll start. My name is Dr. Sarah Howell and I'm the CEO of Aricor Therapeutics. We're a clinical stage biotech developing superior therapeutics for the treatment of diabetes, obesity and some other cardiometabolic diseases. Great. Wendy? I'm Dr. Wendy Lane and I am a clinical endocrinologist and primarily a diabetologist. And I've been in practice for 37 years now in Western North Carolina and the United States. Perfect. Okay, so let's go ahead and kick this off and let's set the background for our audience. So if we zoom out, how would you both describe the current state of diabetes technology? POMs, CGMs, algorithms, new drugs? versus what people actually experience day to day living with diabetes. And I'll start, let's see, start with Sarah. Okay, great. I'll talk a little bit about the tech and then Wendy, I'll hand over to you to talk about the lived experience for people who live in diabetes, because obviously you see these patients every day. So first and foremost, first thing to say is there's been huge advancements in diabetes care and treatment options, but it is still a high burden 24-7. disease to manage. So when we talk about technology, I think here we're really talking about continuous blood glucose monitors that ⁓ measure a person with diabetes, blood glucose in real time. These are now fed to algorithms that can calculate based on those blood glucose readings, how much insulin do they need to keep themselves inside a target blood glucose range. And that's the daily challenge here. And then the insulin is automatically delivered by the pumps. these, so these are so-called automated insulin delivery systems or AID. So this is fantastic technology. If we go back a hundred years when, you know, the first insulin was developed there, insulin was slow acting. We now have faster acting insulin. So act more like a healthy person's pancreas. So absorbed more quickly, bring down blood glucose more quickly, but there's still a way to go there. which I'm sure we'll talk about, and there still needs to be quite a lot of interaction and decisions that need to be made and interactions with the technology from the patient perspective there. So technology is advanced, insulin is advanced, but it's still a high burden disease to manage. And maybe that's a good segue for you, Dr. Lane, to talk about a little bit more detail. Yes. Well, first of all, I'd like to say we've come a very long way. I remember when I started practicing, we only had slow acting insulins. They had to be taken with a syringe, not with a pen, with a big needle. People had to poke their fingers multiple times a day to check blood sugars. And in fact, the meters weren't even that small to check your blood sugar. It was basically the size of a notebook on a table. Then they became smaller, but people still were poking their fingers. So the technology has... really dramatically improve the lives of people living with diabetes, particularly people who require insulin. And diabetes went from being a fatal disease when insulin was first discovered to a disease where you can have a long, healthy, productive life. So that's the good news. Now, are we there yet in terms of making this just a minor nuisance or life like anybody else? And the answer is no, we're not there yet. And even though the technology, particularly the continuous glucose monitors, which read the blood sugar every one to five minutes. And as Sarah was talking about, it'll send it to an insulin pump, which will modify the insulin infusion rate to control the blood sugar within a range. These are great devices. They've improved the quality of life tremendously. The pumps can shut off the insulin now, which we couldn't used to do if the sugar is dropping and prevent hypoglycemia, which can be life threatening. Huge, huge advancement. Is it 100 %? No. the patient still has to take an additional, we call it a bolus or amount of insulin to cover the food and they can make a mistake and deliver too much and once it's in, you can't get it out. So we still see some hypoglycemia and that of course is very distressing and interferes with people's lives. The other thing is the insulins we have right now aren't fast enough. They're delivered subcutaneously under the skin. So even if people have to think, I have to take my bolus of insulin 15 or 20 minutes before I eat. And some of the older insulins and the concentrated insulins, I have to take them a half hour before I eat. Well, who can do that? And so, ⁓ you know, there's still quite a burden of day-to-day thinking. And it's not just, ⁓ I put on my pump and away we go. I have to think about what time I take my insulin. How much insulin do I take to match the carbohydrates in my food? Is my pump working properly? Did I lay on my sensor? And that's why it's reading low. So this is not... ⁓ a carefree state by any means. Is it better? Yes. It's no longer fatal. We have ways to control the glucose and control long-term risk and complications. But are we there where we are equivalent to a person without diabetes? We are still pretty far from that, and we still need to improve on how we deliver the insulin and the types of insulin that we're delivering. Both of you actually have laid out quite well the landscape right now and still So you said the incredible advancements, but also the room for improvement. So let me ask, what are the biggest myths or practical barriers you see that keep pump adoption so far below its potential? Sarah, I'll start with you. Yeah, and you're right. So if we look at the US and zoom into the US where actually pump adoption is the highest, it's higher than we have here in Europe, still only 40 % of people with type 1 diabetes. And only around 5 % of people with type 2 diabetes use these pumps and use these AID systems, despite the fact that there's a huge amount of evidence out there showing that people that move from multiple daily injections through to continuous infusion on pumps do much better. They have better time in range, which leads to better HbA1c, better outcomes. you're right. So why, how do we increase adoption? What's stopping people moving across? And there's a whole myriad of challenges here, and this is what we looked at, but part of this is if we look at the type two patient population, for example, only 5 % of them using pumps. Now the fact is, again, looking at the US here, that around half of people with type two diabetes need more than a hundred units of insulin a day. And that means with current insulins that are available to them and current pumps, They can't even get to a three day standard of care wear time. they'll run out. Sorry, but that's incredible when you're saying that hundred. Yeah, exactly. You know, that's your pretty average type two diabetic patient now who requires insulin. And so around 50 % of them are not getting to standard of care of three day wear. And that means So if they're wearing a patch pump that's disposable, they've got to throw it away. They need another patch pump. They need to fill it with insulin. need to apply it. Quite a lot for them to do, a lot of burden, but also they're going through a lot of pumps and consumables here. That's expensive. The payers won't pay for that. And then really we're looking at people want to fit and forget, I think is the idea. And I think Wendy was alluding to that. But if you, and that means wearing these pumps for longer. and preferably for them to be much smaller. But if we look at that type two patient population, if we go to seven day wear, almost all of them can't get to seven day wear without running out of insulin. And it's a type one problem as well. Over 50 % of the type ones also can't get to seven day wear. So that's a real challenge because it means more interactions with the pump, more changing around of infusion sites. and more consumables, more costs. So there's lots of barriers there that make it a high burden, high cost therapy, even though again, we know they will do better if they move across to an AID system. perhaps Wendy, I'll let you ⁓ talk a little bit more about the patients and the barriers as well, because you see this every day. I sure do. Yeah. So basically what Sarah said, everything I echo, everything she said. It's all true. But I'd like to point out that people with type 1 diabetes are needing almost as much insulin as the people with type 2 diabetes. And even though, like you said, in the US we have the most adoption of technology, we also eat the most ultra-processed carbohydrates. And so that leads to, sadly, the obesity epidemic that parallels the diabetes epidemic. We know that leads to type 2 diabetes. But now it's leading to this entity we call double diabetes, where people with type 1 diabetes who didn't used to be obese, now have similar obesity rates. And when you are obese, you're resistant to the action of insulin. You need much more insulin. So most of the patients I see in my practice, you could look in the waiting room and know who had type 1 and who had type 2 by their body habitus, whether they were using automated insulin delivery, that kind of thing. Now there's so much of an overlap. Everybody needs a high insulin dose because it's weight related. so as Sarah said, it's a challenge to get enough insulin, 100 units a day for one of my patients would not be very much, believe it or not. Now, the pumps hold anywhere from 200 to 300 units for the largest cartridges. And that's of a U100, so a concentration 100 units per milliliter. So they hold two or three milliliters. And that's all our options. And so imagine you needed, and this would not be unusual if you were a very overweight, obese person with diabetes, either type 1 or type 2, you might need 400 or 500 units a day. The other thing is on top of, let's think about physiologic situations that aren't even related to obesity. Teenagers, they're all insulin resistant. And a lot of the teenagers now are sadly overweight or obese. Pregnancy, ⁓ dear God. People's pregnancy insulin requirement from the beginning to the end can triple. And a lot of women now, even with type 2 diabetes, they didn't, they used to be older women who didn't really get pregnant because they were older. Now the young women are getting type 2 diabetes, so they're already insulin resistant. Now they're getting pregnant and they might need 600 units of insulin per day. So they would be changing a pump cartridge twice a day on the largest cartridge. typical day is trying to figure out how to get enough insulin into people. And that's both type 1 and type 2, and even teenagers. And the other thing is there's a sort of a shortage. I don't know if it's true in the UK, but in United States, expert diabetes care is lacking. And so I think the primary care don't feel comfortable with the technology, and they don't feel comfortable especially because right now there's no on-label way to put a concentrated insulin into a pump. And of course, Sarah mentioned the access and the affordability. And of course, the payers, you if you're changing out your device every day or God forbid, twice a day, there's no payer that's going to cover that many cartridges or pods. I'm just curious for what are some of the underappreciated ways where real life movement and work environments drive pump failures, site issues or non-adurance, and how could design and training respond better? You've both done a great job of illustrating. the range of where this sounds to me for my ears, incredible amount of insulin is needed really across kind of the demographic areas and how we're seeing it so much more now. But I just want to go back to where do we see to this impact upon day to day with patients? I mean, people want to be able to live their life freely, right? They want to be able to know that their diabetes is under control, that their glucose is under good control without them having this high burden of interacting with the system. But also then if it's a kind of wearable pump, wearable AID system, they want it to be small. Because if you're wearing, and you'll have seen people wearing pumps or all sorts of wearable devices now on the back of arms. But if that's protruding out of your arm, you can catch that on things. And people are not just automatically necessarily sitting at a desk. They want to play sports or they want to be active. might have a very manual labor job that means so. there's the one piece about it being a really visible indicator if you've got a chronic condition. So people want it to be minimized as much as possible. But then there's a practical element, which I think is what you're asking around, around the size of these pumps. These are large. If you look at a child, these are still It's a large amount of real estate on their body effectively to wear these pumps. So, you know, there's a real need there to miniaturize them and make them smaller. So they're practical for day-to-day living. I'm curious about insulin and diabetes in the realm of GLPs. In our initial discussion, we talked about how there's a perception that we have GLPs, so diabetes will be going away. We're to worry about this anymore. I think you made a really good point, Wendy, in our discussion of that's actually not the case at all. So let's get into that a little bit. How is that narrative helping or harming care? And I think what's some more realistic picture for patients about insulin control when you have GLPs? Yeah, so basically the GLP ones are life-changing drugs. Let's face it. They really are. ⁓ Their main use, yes, they do very well in terms of treating patients with obesity and type 2 diabetes, but all type 1 patients by definition cannot make insulin at all and never will. Unless we get to a point, which we're hoping to, where we replace the cells that make the insulin. At any rate, right now, today, ⁓ all type 1 diabetics or people with diabetes will need insulin replacement. And because of the obesity epidemic, they will sometimes need quite a lot of insulin. And there's no getting around that. We do use a lot of GLP-1s to reduce the insulin requirement, but it's not going to make the insulin go away. And a lot of them, even though you reduce the insulin requirement, it's still, it goes from like 300 to 200 units a day, or 200 to 100 units, still quite a big insulin burden. It used to be, before the GLP-1s, about 50 % of people with type 2 would need insulin replacement because their pancreases had burned out, if you will, and they could not make enough insulin after 10 years. And I suspect that number will go down from 50 % because of the GLP-1s. The problem will be catching them early enough because once they begin to lose beta cells from hyperglycemia, ⁓ there can be ⁓ inexorable loss of beta cell insulin production that we can't fix at this time. Now, if you catch it early enough, you can reverse it with GLP-1s. there's still a... Remember, this disease is asymptomatic, type 2. for a long time. Many of these people haven't even been diagnosed and have had it for years. And the way they present is they lose vision in an eye or their doctor just checks the lab and their sugar's 300 and they didn't even know it. Now you can minimize that with GLP-1s and you can, you know, reverse some of it, but it's not going away. And a lot of these people who don't tolerate GLP-1s, it's about one in five, get too many adverse GI side effects. They are not candidates for this. That makes sense. So I think for just to round up our final question here is that, so in terms of the future, which is always a nice way to end a podcast. So what would a genuinely patient centered diabetes tech ecosystem look like to your cells in terms of device size, wear time, data burden, affordability? Obviously there's a lot of different factors even within what I just said here. But if you talk about your crystal ball, your hopeful crystal ball, where would we be? Yeah, so I mean, think the holy grail for patients would be a body wall system, preferably all in one. So it's one small kind of disc that's your insulin pump with your algorithm and your continuous blood glucose monitor, all integrated into one system, which you could wear for as long as possible. So at least seven days, maybe two weeks. that has very fast insulin inside it. Obviously that insulin would need to be concentrated as well so that you could get it into that kind of small volume, which then you don't have to interact with. You can put that on, you have all the technology. It's managing your blood glucose while you get on with your life. You don't have to announce a meal. You don't have to tell it how much you're going to eat, count your carbs. because the insulin is fast enough to deal with all of those fluctuations and those swift rises in blood glucose. So it is that kind of fit and forget model as much as you can. And you know, we say this, it's not sky-fying. This is all possible. The technology, the pumps have moved on significantly. I mean, when he was talking about the insulins, the very first pump was a backpack. The next leap, miniaturizing them again, is feasible. And you're talking a 10-year timeframe. It's not something that's going to take 20, 30 years. Well, that's exciting. Wendy, final words to wrap that up? Yeah, I think that we have the pieces of the components of a very user-friendly insulin delivery system. Of course, I would like to see a cell replacement in my lifetime for my patients. But until then, what Sarah said, we can get smaller is better. unobtrusive, you know, ⁓ a small, you know, quarter size in the US quarter size device that has can meet the insulin requirements of all patients. So the algorithm of the pump needs to be able to deliver all insulin requirements. So we need a pump that can deliver ⁓ regular insulin requirements with very precise microdosing of both the basal and the bolus insulin. But for patients with larger insulin requirements, we need an ultra rapid insulin in that. pump ⁓ that can hold a week's worth of insulin. And that would have to be ideally like a U500 or even a U1000 insulin. ⁓ combined with a glucose sensor and an algorithm, and the pump insulin has to be fast acting. So as Sarah said, it would be ideal that you didn't have to announce carbs. Or maybe you could tell it, just give it a little tap and say, I'm eating now. And it would have an algorithm that would sense the rise in the glucose. And then quickly figure out, ⁓ this is food intake, and ⁓ deliver what we call the bolus without the patient having to do any calculations or put in any carbs. And then we want it, of course, to be fast in, fast on, and fast out, which means it's not going to have this big long tail on it the way our current concentrated insulin, U500 insulin, lasts too long. So you can cover your food just fine. And we don't have any insulin that can do that for high insulin requirements or to miniaturize a pump right now. That's what we want to see, that's we're working for. Well, on that end, thank you so much, Sarah and Wendy. I like that we're ending at a very optimistic viewpoint for the future. This has been a fascinating discussion talking about the current environment in diabetes, insulin, where we can go with pumps. If you'd to listen to more episodes of Denatured, please turn into biospace.com. And thank you very much.