The Future of CGM Use in Type 2 Diabetes
The Future of CGM Use in Type 2 Diabetes
Hello, and welcome to season two of Diving Into Diabetes, the podcast where we explore the latest advances in best practices on individualized diabetes care. I'm your host, Dr. Ron Goldenberg, and today we'll be discussing the utility and potential benefits of continuous glucose monitoring in type 2 diabetes, it's a pleasure to have with me today, Dr. Ilana Halperin. She's an endocrinologist at Sunnybrook Health Sciences Center and an assistant professor at the University of Toronto. Importantly, she has a very large diabetes practice with a special interest in both young adults and an adult woman and has been recognized as a national expert in the application of diabetes technology to improve the lives of people living with diabetes. So welcome, Dr. Halperin. I'm very excited that you could join us today to discuss this important topic. Thank you, Dr. Goldenberg. I'm thrilled to be here. Great. Once we got started, and traditionally, and for many years, we only used self-monitoring of blood glucose or capillary blood glucose testing as the method for glucose monitoring. Maybe we can discuss the drawbacks of this type of monitoring before we get into the potential differences or benefits of continuous glucose monitoring. Certainly, Ron. I think we know that when you do a finger stick or a capillary blood glucose, you see a moment in time. That moment in time is helpful, especially if it's before a meal and you're trying to decide how much insulin you need to give. Maybe it's before you go to bed and you want to make sure you're not at risk of going low overnight. But even if you check your blood sugar six to eight times a day, which we know most adults with diabetes, especially those with type two, are not going to do, that is still about 23 hours a day where you're sort of driving with your eyes closed. And you don't know what's happening with your glucose values. And we have probably lots of underdiagnosed hypo and hyperglycemia. And we can all think of those patients in the clinic where they check just their fasting glucose every day. Their fasting glucose looks good, but their A1C is above our personalized target. And so that's where the limitations are with capillary or finger prick glucose testing. They're great in production. So I guess when we drive a car, we have to look through the windshield. When we treat diabetes, we need a continuous viewpoint of the glucose over 24 hours. But Dr. Helper, the terminology is a bit confusing because we've had flash glucose monitoring, which I understand has recently had a name change and a general term of CGM. And then there's real-time continuous glucose monitoring. Can you give us a capsule summary of the terminology? So as we move through our discussion today, our audience will have an idea of the terms that we're mentioning. Certainly. So I like to use the term glucose sensor as an overall catchphrase, as opposed to including the C. I like to first describe to our listeners how a glucose sensor works and that it measures something different than capillary blood glucose. So glucose sensor is a soft, flexible filament that sits under the skin and constantly measures the glucose in the surrounding interstitial tissue. And so your glucose sensor value and your finger may poke blood glucose will not be the same because they're measuring two different compartments. So we can talk about accuracy if you want, but I think that's an important first step. And so under the glucose sensor category, we have two main types of sensors available here in Canada today. We have the intermittently scanned continuous glucose monitors, I.S. CGM, which we used to call flash glucose monitoring, and we have the real-time CGM, the RTCGM. And I think that in the next couple of years, we're going to find that there's these terms are already going to become outdated because there are going to become more similarities and differences. But for our listeners in Canada today, most people who are using an intermittently scanned CGM are using the freestyle, liberated device. And the reason it's called intermittently scanned is because the glucose is not pushed to the patient. The patient has to pull the glucose from the sensor that they wear on the back of their arm. And they can do that with an app on a smartphone or with a reader. There's no actual poking or prodding. You just flash or scan the smartphone app or the reader over the device. You get glucose as well as a retrospective look at where your glucose has been over the last eight hours and a trend arrow that tells you where your glucose is likely going. With a real-time CGM, the glucose values are pushed to the individual. Again, that can be pushed to a receiver, an app on a smartphone, or an insulin pump. Real-time CGM also gives you that sort of retrospective look and alerts and alarms. But the big difference is that it pushes the data. And so, we know, I saw a patient in clinic today who's using a CGM like a finger poke. And she only scans when she wakes up in the morning. And her time in range is excellent. But her A1C is high because I'm pretty sure we're missing her post-prandial hyperglycemia. After all, she's not scanning and using the device to the maximum benefit. So hopefully that clarifies the terminology and sets us up for the rest of the conversation. I think it's a great summary, especially for our listeners who don't eat bread and sleep diabetes like us and our endocrinology colleagues. So you know, you get excellent reports from the CGM devices for people who are familiar with the reports. They can be a little bit overwhelming and out of it, interpret them. So maybe before we get into the topic of type two diabetes, you can just give us a brief overview of the key CGM parameters that both clinicians and our patients should be aware of. So that's an excellent benefit of using this technology. Certainly. So I do as an academic endocrinologist, I teach this topic to the residents regularly. And so I like to talk about the ambulatory glucose profile, which has both numeric output and graphical output as the ECG of the endocrinologist. And you know, when you think about retrhythm and access at the beginning, we think about our time in ranges. And so the most important metrics are how much time in this is usually displayed in percentages are patients spending in the target range of four to 10 millimoles per liter below range, which is less than 3.9 and above range. Another really powerful and important metric to look at is variability. I like to look at the coefficient of variability, but other people who may not be familiar with that term might just look at standard deviation. And after you've kind of looked at those metrics, you can also get, if there's enough data, a GMI, a glucose management indicator, which is just an estimated A1C. And that can also be very powerful because perhaps your patients made a change to their medications in the last two to four weeks. And their glucose has really come in range. And the estimated A1C has come down. That may be a number that is meaningful to you and your patient, even though their laboratory A1C does not yet reflect where they're at because the A1C is only going to change after, you know, two or three more months of the new therapy. And so well, we know that there are lots of reasons why we can't rely on A1C because of Hebrew, but empathise and anemia and just the fact that it doesn't give us enough insight into the quality of glycemic control. But the GMI is still a powerful indicator because everyone's so used to focusing on what's my A1C. Well, now I can tell you your estimated A1C based on your time in ranges. And so the target for most adults living with diabetes is to spend about 70 percent of the time in the range with less than 4 percent spent below the range. But I think it's important to remember that one percent of your day is 15 minutes. So that's still an hour a day that we find acceptable for patients to spend in hypoglycemia. And obviously, that's patients who are using insulin, and some of our patients with type two diabetes as we'll discuss might benefit from these devices without a risk of hypoglycemia. But certainly, we'd like to see patients exceeding these goals as opposed to meeting them. Ideally, we have more than 70 percent time in range and no hypoglycemia. The coefficient of variation looks at how many fluctuations are you having from high to low. And that can be within-day fluctuations versus between-day fluctuations. And we know that if we target a CV of less than 36 percent, then the glucose is relatively stable. And that's helpful because when the glucose is stable, you can adjust pharmacotherapy specifically insulin. But the glucose is unstable. The CV is high. And it's much more important to start talking with the person in front of you living with diabetes about what are the habits. When do they take their insulin? How comfortable are they adjusting their insulin based on their exercise or their mealtime? Do they tend to give corrections two hours after a meal because they get a high alarm and then they end up going low? Those types of behavioral changes are what's needed to bring the CV in range. And the last thing I'll talk about is just the ambulatory glucose profile, which is a graphical representation of the glucose over 14 days. And it can be very powerful and help you to identify where the changes need to be. And it's probably more powerful for our patients than any of these metrics we've just talked about because they can see, oh, wow, I tend to go high after dinner. And maybe if I just instituted an after-dinner walk, I would start to see the improvements in my glucose without even making any pharmacotherapy changes. And so that's why these new data that we get from these new devices can be so powerful. Great summary. So just to recap for our listeners, look at the time in ranges, particularly time below range and time in range, I tell my patients to look for the green zone to be higher because green is good and red is bad. Look at measures of variability and maybe the glucose management indicator and the overall profile and the ups and downs. So with that, traditionally for many years, we were using CGM mainly for type one diabetes. Both in MDI or multiple daily injection patients and definitely in insulin pump patients. there's a wealth of data going back many years now showing the benefits of type one diabetes. But as you know, the data were type 2 diabetes is kind of still emerging. Most of the initial trials were done in patients on basal-bolus insulin, kind of like type ones. But recently, there's been more evidence to suggest that we should be using CGM in type 2 diabetes in two populations. One, the basal insulin trait of patients, and number two, even in people not on insulin therapies for type two diabetes. So maybe you can describe to our audience the two important trials. The first is the mobile trial in basal insulin-treated patients, and then the immediate study which is in type two patients not on insulin. So let's start with the mobile study, maybe a summary of why that's an important study in the CGM space for type 2 diabetes. Certainly, Ron, it's a really important study. If not only because it was patients with type two on basal insulin because it was patients in primary care. And we think that that's an important thing for us to put in perspective is the majority of type two diabetes is going to be treated in primary care. And while traditionally these advanced technologies are felt to sort of only be prescribed and managed in specialty clinics, I recently listened to your interview with Irene Ramack and you talked about starting insulin in primary care in the early 2000s and how revolutionary that was. And now we have studies showing that primary care physicians can help patients manage their diabetes using advanced technologies like CGM. So the mobile study took patients who had an average A1C of around 9% on basal insulin and other non-insulin agents and they randomized them two to one to CGM or traditional finger poke or capillary blood glucose monitoring. And they followed up to see what would happen to both the time and range and the A1C. There were no specific titration patterns or guidance or anything like that. It has really been a while since you've been using CGM, let's see how you do. And they had them in primary care with the primary care doctors reviewing their data and making adjustments to their medications. And so at the end of the study, the time and range was only 43% in the CGM group, sorry, in the finger poke group, but up to 59% in the CGM group, which means that the CGM group was spending 3.6 hours more a day in the target time and range. The way they figured out what the time and range was for the group which was the traditional finger poke group was they had them where a blinded CGM for 14 days at the beginning and end of the trial so they could compare across time and ranges. They did look and saw that there was possibly less hypoglycemia in the group that was on CGM, but those were just sort of secondary and exploratory outcomes. The mobile study had a second component to it, which I think is even more important from a clinical practice perspective. So in phase two of the study, they took the capillary blood glucose monitoring group and gave them real-time CGM. Then they took the real-time CGM group and randomized them to discontinue or continue. And so they just looked at that group who initially had CGM in the first part of the study and saw what happened if they continued or not. Unsurprisingly, the gains that were made while they were on CGM were lost when they stopped using CGM. So I think this is important because I think a lot of us would initially conclude, oh, this is a useful tool for helping with basal insulin titration. But once you're at a stable dose, you may not need it any longer. But I think that phase two of the mobile study shows us that it's probably not just about the basal insulin. It's the actual feedback that they get in terms of lifestyle modification that continues to help them stay in range and keep the A1C down. So when you're using real-time CGM, you get to see the impacts of whether you eat salad or pasta for dinner and whether you go for that walk or not. And so probably that's an important piece when we think about whether we're going to use CGM intermittently or continuously for patient care. So if you stop looking through the windshield, you're going to crash. So basically, if you have diabetes and you stop using your CGM, you're not going to get the information that you can get otherwise with CGM. So the immediate study is a little bit different. I've been a fan of using CGM in non-insulin-treated patients for a long time because you learn a lot of things that you wouldn't pick up otherwise. But there weren't good randomized trials to address that. So our group took part in the immediate study in non-insulin treated type 2 diabetes. And maybe in a couple of minutes, you can describe the results of the study and why that's important to clinical practice. Yeah. So certainly, as you said, I'm with you, too, even though it wasn't in the guidelines. I think the biggest limitation for me would be cost and coverage. But if patients could avail themselves of a CGM early in the diagnosis or even at a point where they're seeing me and I'm sort of like, I could add a third agent or maybe you just need a relook at your lifestyle. Let's get you on CGM and connect you with a good diabetes educator. And even without the diabetes educator, they can just learn, like you said, because they're driving, looking for the windshield and they can see when they're going off the road. And the CGM helps them stay on the path. So the immediate study took patients like you and I are discussing and randomized them one to one to use flash glucose monitoring or sorry, intermittently scan CGM, I should say. The group that did not receive the intermittent scan CGM did have a blinded CGM at the beginning and the end of the study. And there was almost a 10% time and range difference between the two groups towards the end of the study with a 0.3% lowering in the A1C at 12 weeks. And that's quite common to what we see in most studies. So while it was statistically significantly different, more importantly, the 10% time and range difference is clinically significant because every 10% increase in your time and range is about a 0.3 to 0.5% lowering in your A1C. And so this could be as powerful as starting some of our second-line agents and potentially offers a lot of other benefits because maybe it helps our patients lose some weight. After all, they are eating better or just increasing their physical activity, which I know you've had a conversation about on the podcast as well, and about the importance of physical activity for longevity and not just diabetes management. So I think the immediate study is really helpful in kind of confirming what people like you and I were doing before. Hopefully it will actually slowly change practice so that we'll have more access to these devices for patients who are not on insulin because again, today I think the biggest limitation is the coverage piece and that people who are not on insulin may not get coverage to use these devices on an ongoing basis. I really like your comment about the effect of putting an individual on CGM is almost like adding another anti-hyperglycemic agent so maybe I asked clinicians we should be aware of that, especially in the context of polypharmacy for a lot of our patients. So we're moving to the end and what we do practice in Canada and Diabetes Canada has tremendous clinical practice guidelines, one component of that are recommendations around glucose monitoring. I think can you tell us that in the most recent iteration of the monitoring guidelines in Canada or the specific recommendations for CGM in type two diabetes and does that kind of match with the studies we just discussed today? So well, I am a huge fan of the Diabetes Canada clinical practice guidelines and I've partaken in many of their chapter updates. We are not that our chapter updates are quickly out of date because both of the studies that you and I just discussed were published after the most recent 2020 monitoring guidelines finished her now almost three years old as we sit here at the end of March 2023. And so those guidelines said that we could may use CGM in patients with type two diabetes for improvements in A1C, that those the main data that they had at the time and it was really focused on patients with type two diabetes on basil, bolus, insulin because that was the evidence they had at the time. But now you and I have just discussed to well done randomized control trials for other populations of patients with diabetes, one that used real time CGM and the other that used intermittently scan CGM, two different populations with different devices. But I think if we had an update in the chapters, these certainly these studies would make their way in and may strengthen the recommendation for the use of CGM and patients with type two diabetes on basil insulin alone or even only on oral or I should say non-insulin hyperglycaemic meds because certainly, many patients are on injectables. Great. Well, thank you, Dr. Halperin. I think that was an excellent conversation on the topic of the utility and potential benefits of CGM in type two diabetes. So thanks to our listeners for joining us in this latest installment of the diving into diabetes podcast.
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