Hello, and welcome to Section 2, Therapeutics, where we will be talking about intensifying diabetes treatment in a timely manner. My name is Diana Isaacs. I'm an endocrine clinical pharmacist, as well as the Director of Education and Training in Diabetes Technology at Cleveland Clinic in Cleveland, Ohio. We have two learning objectives in this section. The first is to review the latest evidence-based guidelines on implementing complication-centric treatment options in persons living with type 2 diabetes. Our second objective is to identify methods to intensify therapies to reach timely, sustained glycemic targets and maintain weight or promote weight loss. In terms of the content we'll be covering in this section, we'll start off with the goals for treatment, really emphasizing individualized targets. Then we'll talk about our medication choices and how to determine which medications to use and what the different algorithms state. We know cost can be a barrier to using medications, and we'll talk about the cost considerations and some programs that may help to reduce the cost. And lastly, we'll finish up with diabetes technology, talking about how it can be a great tool for behavior modification, as well as helping with medication adjustments. Before we dive into things, let's talk about the principles of type 2 diabetes management. ACE updated their treatment algorithm in 2023 and really has these 10 principles for the comprehensive type 2 diabetes management. You'll notice that number one is lifestyle modification underlines all therapy. Number two is maintaining or achieving optimal weight. And then the choice of anti-hyperglycemic therapy reflects glycemic targets, as well as other conditions like cardiovascular disease, the presence of heart failure or kidney disease, presence of overweight or obesity, or the presence of fatty liver disease. The choice of therapy includes ease of use and access. The optimal A1c is less than 6.5%, or as close to normal as possible, as is achievable for most patients. But we also want to individualize our glycemic targets, and we'll be talking about other things in addition to A1c, like some of our CGM key metrics, like glucose management indicator and time and range. Getting to goal as soon as possible is important and not delaying, so adjusting therapy less than or no greater than every three months. We want to avoid hypoglycemia. CGM, continuous glucose monitoring, is highly recommended to assist patients in achieving their goals safely. And then comorbidities must be managed for comprehensive care, including things like hypertension and hyperlipidemia. And now we'll talk more specifically about the goals for treatment. There are two major guidelines that we utilize in the United States. That is, on the left, the ADA, the American Diabetes Association, and on the right, we have ACE, the American Association of Clinical Endocrinology. You'll notice that there are some differences between the goals, although there's actually a lot more similarities than differences. So ADA advocates an A1c target of less than 7% for most, versus ACE is 6.5% or less. And then this corresponds to slightly different pre-prandial versus post-prandial goals. So pre-prandial, that would be fasting or before meals if it had been four more hours since eating. The ADA targets 80 to 130 milligrams per deciliter, versus ACE is really targeting less than 110. Now peak post-prandial for the ADA, that would be the highest it gets after eating, typically occurs one to two hours after the start of the meal. The goal is less than 180, versus ACE has a target for two hours post-prandial of less than 140. But I say there's more similarities than differences because both guidelines advocate that this should be individualized, and we'll see more about that on the next slide. Both organizations advocate individualizing A1c goals. And so for some people that might be less than 6.5% or even lower, or for others that might be a higher A1c target, such as less than 8% or even 8.5%. So what are those factors that might indicate what target to use? Well, one can be the risk of hypoglycemia, especially people that are on therapies like insulin and especially mealtime insulin, where they might have a greater risk. Age and comorbidities. So more advanced comorbidities, as well as more advanced age and shorter life expectancy, all might be reasons to have a higher A1c target. Other considerations are a person's resources and support system, as well as how motivated the person is and what their actual preference is. Some people are happy to be on multiple medications if it can help them to get that lower A1c target, and for others, they really want to minimize any potential side effects and want to be on less medications or may just not have a support system where it makes it easy to be able to achieve those targets. We also think about the duration of diabetes. Longer-standing diabetes can make it more challenging to reach those lower A1c targets. And then other things are the established vascular complications. Those with more advanced complications may have a higher A1c target compared to a newer diagnosed person that does not have any complications. While A1c has long been a marker that we use to assess glycemic management, it does have some limitations, mainly that it's based on an average and it doesn't tell us anything about glucose variability. So what you're seeing in this image are actually three different profiles of an A1c of 7%. And number three would kind of be that optimal where there's low variability. And most of the time, the glucose levels are between 70 and 180, which is what we consider the target glucose range. Number two, though, is showing someone with a lot of glucose variability who's going pretty high and also pretty low. And that's not what we want. But unfortunately, when all you have is an average, you don't know if a person could be experiencing some unrecognized hypoglycemia. Number one is showing someone with medium variability where there's some hypoglycemia and hyperglycemia. When we utilize continuous glucose monitoring, or CGM, we get a lot more information. These are devices that actually measure glucose, typically every 1 to 5 minutes, and record that data every 5 to 15 minutes. And so we get information about time in range, as well as time above range and time below range. And this is part of the ambulatory glucose profile. And typically, we're aiming for maximizing that time in that target range between 70 and 180. And it's been described that spending 70%, at least 70% in that range, correlates pretty well with a less than 7% A1c. And a good way to think about this is each 1% of time is equivalent to about 15 minutes of the day. In addition to the target of 70% or more in range of that 70 to 180, we also have targets for time below range, or that time spent in hypoglycemia. We're trying to minimize that to less than 4% for most people, below 70, and less than 1% below 54. For time above range, we're trying to minimize that to less than 25% of the time over 180, which includes less than 5% of the time over 250. Now, for those that are older, or higher risk, or have more advanced comorbidities, where we might be shooting for that higher A1c target, maybe less than 8%, the priority becomes to really minimize hypoglycemia, that time below range, even below 70 to less than 1%. And we aim for at least 50% or more in that target range of 70 to 180. And we still try to minimize that time above range to less than 10% for over 250. Now that we've talked about how to individualize glycemic goals, next, let's talk about the medication options that we have that we can utilize to get to those glycemic targets. It turns out we have a lot of medication options to treat diabetes. We have the biguanide, metformin, we have sulfonylureas, drugs like glipizide and glyburide, we have glitinides, drugs like nitaglinide, repaglinide, we have the thiazolidinediones, like pioglitazone, we have DPP-4 inhibitors, drugs like sitagliptin, we have the glucagon-like peptide 1 receptor agonists, or GLP-1 receptor agonists, drugs like semaglutide, dulaglutide, and then, more recently, we have the dual-incretin GLP-1 and GIP receptor agonist terzapatide. We have SGLT-2 inhibitors, drugs like hanagliflozin, ampagliflozin. Less commonly known, the bile acid sequestrant colicevelum actually has an FDA approval for type 2 diabetes. This is also used for cholesterol lowering. And then, also less well-known, the dopamine 2 agonist bromocryptine controlled release. Usually, we think of bromocryptine for Parkinson's disease, but in the controlled release form, there is actually an indication for type 2 diabetes. There's the amylin mimetic, pramalentide. We also have alpha-glucosidase inhibitors, drugs like acarbose, and then, of course, there's insulin. That's actually 13 drug classes. And then, of course, we have glucagon, which is used to treat severe hypoglycemia. Why do we have so many drug options for diabetes? Well, it turns out there's several different targets that are known, and the idea is that the more of these that we can target, the better outcomes we'll have in diabetes management. Here's what you're seeing is the ominous octet, which was described by Ralph DeFranco, eight different areas that we can target in diabetes management. Starting off with the pancreas, we've got alpha cells and beta cells. The beta cells aren't secreting enough insulin, so either giving insulin or using drugs like secretagogues to allow for more insulin release is a target. There also tends to be too much glucagon, which then causes increased hepatic glucose production. So drugs that target the glucagon, like GLP-1 receptor agonist or the dual GLP-1-GIP receptor agonist, also drugs that target the hepatic glucose production, like metformin, can help. We've also learned that there's some neurotransmitter dysfunction. In the brain, satiety signals may be affected, and drugs like the GLP-1 receptor agonist affect there. Also, it's thought bromocryptine-controlled release may affect circadian rhythm, and that can be a target for that neurotransmitters. Decreased glucose uptake in the muscles, and so a good example of this would be like pyoglitazone, the TZD. We also see that there's increased glucose reabsorption in the kidneys, and SGLT2 inhibitors target that. There also tends to be increased lipolysis, and the TZDs, again, target this pretty well. And then also the decreased incretin effect, which can affect gastric emptying, amongst other things, satiety, and so the GLP-1 receptor agonist, the dual GLP-1-GIP receptor agonist, as well as DPP-4 inhibitors target this as well. So we have a lot of choices for diabetes agents. Fortunately, the ACE guidelines provide a nice summary of the different effects of all of our different drug classes, including things like the efficacy for glucose lowering, as well as impacts on things like cardiovascular disease, kidney disease, and then if there's need for renal dose adjustment, if there's any hypoglycemia risk, or what are the impacts on weight and fatty liver disease, if there's GI adverse effects, and other special considerations, as well as things like access and cost. And one of the areas that I do want to highlight on here are the impacts on cardiovascular disease, including the things like MACE, major adverse cardiovascular events, heart failure, and stroke. Fortunately, all of the drugs since 2008 have cardiovascular outcome data where they're studied to show that they have safety. And in doing this, many have actually gone on to show that they're not only safe, but they have benefit in these populations. And so that's what you're seeing here. For example, with the GLP-1 receptor agonist, the benefit for MACE and for stroke, you're seeing that for the dual GLP-1 receptor agonist, GIP, that it's considered to be safe. And then for SGLT2 inhibitors, seeing that benefit for MACE, reduced risk for heart failure, and possible benefit for stroke. And so this provides a great, great summary for all of these different areas. So how do we decide what agents to use in the treatment of diabetes? Well, fortunately, our guidelines provide nice algorithms to help us determine. What you're seeing here are the guidance from the ADA. And what you'll notice is that based on the cardiovascular risk profiles, we recommend certain agents. So on the left, for those with atherosclerotic cardiovascular disease or have indicators of high risk, we recommend using a GLP-1 receptor agonist with proven cardiovascular disease benefit in this population. So that would include semaglutide, liraglutide, or dulaglutide. Or you could use an SGLT2 inhibitor with proven cardiovascular disease benefit in this population, which would include empagliflozin, canagliflozin, or dapagliflozin. And then if anyone sees above target, choosing one of the agents you haven't used already from the other category or a TZD is an option. For heart failure, SGLT2 inhibitors clearly have the most benefit for this population. And then when it comes to kidney disease, using an SGLT2 inhibitor can be protective, especially utilizing one of the ones that showed the benefit. And that includes dapagliflozin, canagliflozin, and empagliflozin, or using a GLP-1 receptor agonist with that proven cardiovascular disease benefit. Now, what if someone doesn't have one of these high-risk cardiovascular risk factors? Well, then we want to choose agents based on their efficacy for glucose lowering, especially if we're starting off with a higher A1c or that lower time and target range. And very high-efficacy agents include things like dulaglutide, semaglutide, interzepatide, as well as insulin or combination therapy using like metformin plus one of these agents. Now, many people with type 2 diabetes have this dual goal of not just glucose lowering, but also weight management. And so, if we're choosing agents that really will have the most powerful impact on lowering weight, very high would be semaglutide and interzepatide. And then when it comes to high, that would be dulaglutide and liraglutide. Intermediate is considering a GLP-1 not listed already, like exenatide. And then an SGLT2 inhibitor. And then neutral would be your DPP-4 inhibitors or metformin. Now, ACE has very similar guidance in their type 2 diabetes algorithm. If cardiovascular disease or high risk, they recommend that GLP-1 receptor agonist or SGLT2 inhibitor. For heart failure, recommending SGLT2 inhibitor. They also include in theirs stroke or TIA, in which case GLP-1 receptor agonist or pyoglitazone is actually recommended. And then for kidney disease, we see an SGLT2 inhibitor or GLP-1 receptor agonist. And if not at goal, continue or start metformin as appropriate, as well as adding one of the therapies that was not previously used. Now, what if someone doesn't have one of those complications? The ACE also has a glucose-centric algorithm as well. And you'll note the foundation are, of course, lifestyle interventions. As well as for most people without comorbidities like heart failure, cardiovascular disease, or kidney disease, we're going to be starting metformin as first line. Versus if they have one of those other indications, irrespective of glucose target or metformin use, we're going to use one of those agents that shows that cardiovascular protection. Now, in this case, it's split up for those with overweight or obesity, in which case preferred agents are going to be GLP-1 receptor agonist, our dual GLP-1-GIP receptor agonist, or SGLT2 inhibitors. For hypoglycemia risk, those are also going to be our preferred agents because they don't cause hypoglycemia. If access and cost is an issue, then utilizing an agent like a TZD or a sulfonylurea or glitinide can be good because those are all available as generic options and will be lower cost. And then for severe hyperglycemia, so often that would be like an A1c over 10% or glucose that's over 300, we're going to go right away and start basal insulin or basal plus prandial insulin. And also utilizing very effective glucose-lowering therapies like our weekly GLP-1 receptor agonist or the dual agonist. And then for those that have A1c's that are over 7.5%, starting with two agents can often be a great strategy versus just starting with one and waiting, going ahead right away and starting with two. You'll notice that there's alternatives listed for each one and then also a concern or not preferred. So for example, for those with overweight or obesity or hypoglycemia risk, you really would want to go ahead and avoid the sulfonylurea or the glitinide. If cost is an access or major concerns, then you'd want to be careful about using GLP-1 receptor agonist or the dual incretin or even SGLT2 inhibitors because those can be higher costs and they may not be preferred. Although we are going to talk in a little bit about some strategies to be able to obtain those agents. And then it says to titrate to maximum tolerated doses. And also you can consider other agents listed on here as well at the bottom if someone's not meeting their goals. And so you'll notice in this algorithm, they have listed some of the less commonly used agents like colicevelum, bromocryptine controlled release, as well as pramlentide. For type 2 diabetes management, we usually try to utilize our oral agents and non-insulin injectables. Over time, though, due to the progressive nature of type 2 diabetes, people may require insulin. We typically start with a basal insulin or a long-acting insulin, and we have several different choices available. We now have ultra-long insulins, which typically last well beyond 24 hours. And include things like Glargine U300, as well as Deglutat, which comes in a U100 and U200 formulation. We also have our longer-acting insulins that are close to 24 hours, sometimes a little bit shorter. That includes insulin Glargine, as well as insulin Datamir. And then an oldie is intermediate insulin, NPH, which typically does have a peak and needs to be dosed down. Does have a peak and needs to be dosed twice daily to have that full 24-hour effect. Although in people with type 2 diabetes, sometimes taking one dose of NPH in the bedtime can work at least to lower that fasting glucose level. And then for those that require mealtime insulin, we have several options. Regular insulin needs to be dosed 30 minutes before meals. And you'll notice it lasts a little bit longer in the system, so can predispose to more hypoglycemia. Compared to now, we have several faster-acting insulins, which includes Aspart, Lispro, and Glulosine. There's also inhaled insulin as well, which is a little bit faster than the injectable rapid acting insulins. In terms of starting insulin, generally we're going to start with a basal or long acting insulin. Now before even going here though, if someone's not already on a GLP-1 receptor agonist, this is typically recommended as the first line injectable agent, so we always want to assess for that first. If they're still not meeting their goals, then we can start that basal insulin. And if A1c is less than 8%, typically a total daily dose to start of 0.1 to 0.2 units per kilogram per day works well. If they're up an A1c of greater than 8%, then starting off straight with 0.2 to 0.3 units per kilo per day. And then we can continue to adjust this every two to five days to really reach the glycemic goals. And at this time, it's a good idea to discontinue or at least reduce a sulfonylurea if someone's on that. And basal analogs like our longer acting basals like that Glargine or Daglodac are generally going to be preferred over our intermediate acting like NPH. And also we've got some guidance here. If there's hypoglycemia, reducing that total daily dose. If there's glucose levels below 70, going down 10 to 20%. Or if it's less than 40, decreasing even more by 20 to 40%. You do want to be cautious about basal doses getting beyond 0.5 units per kilo per day, or what's called a beam score. When bedtime to morning glucose drops by more than 50 points without giving any insulin, like any fast acting insulin right before bedtime. That could be a sign that someone is over basalized, that they're just getting too much long acting insulin without any prandial insulin coverage. And in this case, what we would want to do is add some prandial insulin. So a good approach, you can do a stepwise approach where you begin prandial insulin either before the largest meal or the meal that causes the greatest glucose excursion. And rapid acting insulins like your Aspart, your Lispro, your Glucosine or inhaled insulin are generally going to be preferred over your regular insulin. And in this case, we can titrate the insulin every two to three days to reach those glycemic goals, increasing the pre-meal dose by 10 to 20%. Aiming for that pre-meal blood glucose of 110 to 140. And for hypoglycemia, any pre-meal blood glucose that's less than 70%, we'd want to go ahead and decrease by 10 to 20% for that previous meal. Now that we've talked about all of our medication choices and how we select them, next, let's dive into some cost considerations. So there are several lower cost medication options that are available as generic and often can be purchased for like $4 a month or $10 for a three month supply. That includes metformin, which for those without other comorbidities is often our first line agent. It's available in immediate release and extended release. We do have to be concerned about the common side effect of diarrhea or loose stools, which can often be helped by using the extended release or taking it with food. With TZD or thiazolidinedione, potential side effects of this include edema or weight gain. And that includes the drug pioglitazone, which often has beneficial effects for stroke as well as fatty liver disease. Sulfonylureas, so this includes drugs like glibizide, glimepiride, gliburide, which are all available as generics. Side effects, though, we do have to be concerned about hypoglycemia as well as weight gain. With TZDs, we can also see edema and weight gain. And then insulin, so there are many lower cost insulin options. Regular insulin and MPH are often available for $25 a vial or a low cost pen pack. There's also several insulins now that are follow on or generics which have lower costs. And side effect profiles we need to worry about this are hypoglycemia and weight gain as well. When it comes to affordable insulin, fortunately, there are many different options. So generic insulins are often a lower cost. These are insulins that are made by the same manufacturer and are actually identical to the reference product. They're just marketed as the generic. So examples include insulin Glargine, insulin Aspart, and insulin Lispro. There's also several follow on biologics that are available at a lower cost. And some are even interchangeable, meaning that if you prescribe for one, the pharmacist can change for another if it's a lower cost. Because insulin is a large peptide molecule, creating a generic as you would for a tablet is more challenging. And so that's why these are considered follow on biologics. And for example, with insulin Glargine, which is the reference product for Lantus, some follow on products include ResvoGlar, Semgly, and Basaglar. And actually, both Semgly and ResvoGlar are considered to be interchangeable with Lantus, meaning if you prescribe for Lantus, it could get changed to Semgly or ResvoGlar if that's going to be a lower cost for the patient. And then insulin Lispro is also the reference product for Humalog. And so some follow on products for Humalog that includes AdmiLog. So unfortunately, many people may not be adequately managed on some low cost alternative medications. And as we saw, there can be more side effects with certain agents as well, like hypoglycemia or weight gain. And then not all of these agents, like sulfonylureas, for example, don't show the cardiovascular benefits that we have with our other agents, like GLP-1 receptor agonists and SGLT2 inhibitors. Fortunately, there are several cost savings programs that can help people with diabetes obtain other medications. So those include things like manufacturer patient assistance programs. And these often have an income threshold, although they often are higher than people might realize, going up to the 300 or even 400% poverty level. So based on someone's income and family size, they may qualify for these programs. There's also several copay cards that are eligible for people with commercial insurance. So people should always check to see if there's a copay card for their medication that they can utilize to bring down that price. And then there's also several third party discount card programs. Those are things like GoodRx, where people can check to see if there's a lower cost option available that they could pursue. Some additional cost saving strategies include utilizing combination products. So that's where you can get two medications instead of one. And this may allow for one copay instead of two. And a couple of good examples are the GLP-1 insulin combinations, Selequa, which is a combination of insulin glargine with lexysenatide. And then Zoltify, which is a combination of the long-acting insulin Deglidac with Leroglutide. Using generics whenever possible, although again, the SGLT2 inhibitors and GLP-1 receptor agonists do not have generic options quite yet. Using those follow-on and generic insulins. And then also there's things like Walmart insulin or other places that have lower cost alternatives, especially for Novalin N and Novalin R. There's also a rely on form of Novalog insulin aspart, which is a lower cost. It's $73 a vial or $86 for a pack of five pens. So those are some additional strategies. Also, several medications do have free trial offers. Now, this is not a long-term solution as this is typically 14 to 30 days. However, many medications do require prior authorizations and this can at least get a person started while they're waiting for that prior authorization paperwork to get through. Also, some companies have like a one-time immediate supply. So for example, Novo Nordisk has the one-time kind of emergency supply where you can get up to three vials or two packs of pens. And then some offices do carry samples. I wanna stress this is definitely not a long-term solution, but in a bind, this can get someone through. And then Medicare recently capped their monthly insulin cost to $35. And so this can really help to at least make insulin affordable. And also, this $35 cap even includes the combination products like the GLP-1 with insulin, so that is a way that people can also obtain their GLP-1 for this lower cost that have Medicare. And finally, here are some various clinical scenarios and options. So if you have a person that's enrolled in Medicare, which is typically the 65 and over adults, you can look for an insurance plan formulary alternative. For example, there might be a preferred SGLT2 inhibitor or GLP-1 receptor agonist. Certain people may be eligible for patient assistance programs as long as the conditions have been met in terms of the income requirements. And then also, this population qualifies for that $35 capped insulin. And as a reminder, this also includes this combination insulin GLP-1 receptor agonist products. For those that have commercial insurance, here's where you can look at insurance plan formulary alternatives. Often there may be one agent that's preferred over another, completing prior authorization paperwork. And then also, this population's eligible for the manufacturer co-pay cards. Just pay close attention to the max savings with each card because that can vary. And some cards may say, as low as $10 or $0 a month, but it only covers $100 off the drug. And if the drug is $500 or $1,000, that's not gonna save very much money. Some cards do pay down quite a bit, so just you can look at that. Now, what about a person that's on their state Medicaid program? So often here, there are certain formularies that you can look up online. And so making sure you choose the drug that's on the person's formulary, and going through the prior authorization process as needed. And then for those with no insurance, this population is eligible for those manufacturer patient assistance programs. Each insulin manufacturer has programs, like Sanofi has the Insulin Value Program. Novo Nordisk has the My $99 Insulin Program. And Lilly has a $35 program that patients can be eligible for insulin. Also looking at the human insulin or generic types of insulin. And also looking to a referral site for a free clinic or pharmacies that are affiliated with the 340B status. And now for the last part of this section, we are going to talk about diabetes technology. So coming back to CGM, we talked a little bit about this in the beginning, when we talked about glucose targets. As a reminder, these are devices that measure glucose every one to five minutes and record it every five to 15 minutes. If you do the math, that's actually 288 readings per day. They are measuring the glucose in interstitial fluid, as opposed to finger sticks, which actually measure in the capillary space. So there sometimes can be a tiny bit of lag time when glucose is rising or falling rapidly. And then there's three components of these. There is the sensor, which is that little filament that's just below the skin. And then that is communicating through a transmitter to some type of receiver or reader, which often can be a smartphone. And the transmitter, depending on the device, is either disposable and attached with a sensor, or in some devices, it is reusable. Some even require charging in between use as well. This highlights the difference between BGM, blood glucose monitoring, versus CGM, continuous glucose monitoring. And so what you're seeing here, these four dots represent BGM. So a person that's checking maybe before their meals and at bedtime. The green represents that target range of 70 to 180. And this is basically representing a 24-hour time period. And so if all you have are those finger stick readings, you might make assumptions about someone's glycemic management. Such as, in this case, it looks like it all is at goal. However, when you have that full 24-hour picture of CGM data, we actually see there's some undetected hypoglycemia. And especially alarming, that's even occurring overnight. And then we also see that there's some undetected hyperglycemia, likely occurring after meals. And so this is a very different picture compared to just that BGM. Another advantage of CGM, in addition to being able to see that whole glycemic picture, being able to assess time and range and glucose variability, is that it provides real-time data for people living with diabetes. And so they can know what their glucose level is, in addition to the direction that it's going. As well as getting alerts in real time for high or low glucose values. And for example, if you look at these first three images, a 110 with that arrow steady versus a 108, that arrow's going down, and a 112 with the arrow partially going up. These are three very different scenarios. Let's say a person was getting ready to drive in their car or exercise. Well, if they did a finger stick and saw any one of these numbers, they'd probably think, okay, I'm in the safe zone. It's safe to go and exercise or drive my car. But what about this middle scenario, where it's the 108 with the down arrow? This means in the next 15 or 30 minutes, this person may be experiencing hypoglycemia. And by being able to see that arrow, the person can actually take action and treat it and do something about it before they actually go low and experience hypoglycemia. There's actually two categories of CGM. There's real time, which provides the readings without any action. And then there's intermittently scanned or flash CGM, which requires an action of scanning the sensor to be able to see the glucose reading. So the ACE actually has a nice little algorithm of matching glucose monitoring option to the complexity of the anti-hyperglycemic regimen. And so when would you maybe rely on capillary glucose monitoring, blood glucose monitoring, or BGM versus reliance on CGM? And so if you're utilizing agents that have a very low hypoglycemia risk, such as just SGLT2 inhibitors or GLP1 receptor agonists, then in that case, reliance on more BGM may be appropriate. And as you start to go up the ladder here, as you have increased complexity or increased risk of hypoglycemia, that's when it might be better to rely a little bit more on CGM. And so up this ladder goes the oral insulin secretagogues, that's like your sulfonylureas and your glitinides, basal insulin. When you get into the multiple daily injections or use of smart pens, that's gonna increase the hypoglycemia risk. And it includes other forms of technology on here as well, like the smart pens. We also have patch pumps, which are kind of a wearable way of taking insulin, as well as more advanced insulin pumps and even sensor augmented pumps that rely on CGM readings to adjust the insulin delivery. And so as you get higher up here, you're definitely gonna wanna rely more on CGM as opposed to BGM. I'd like to close out with a case study and showing how we can utilize CGM to help with medication adjustments and even with deprescribing. So here we have Susie, she is 73 years old, living with type 2 diabetes, coronary artery disease, status post stent placements, and chronic kidney disease. Her weight is 288 pounds, BMI is 56, most recent A1C 7.5%, GFR is 40. She did try an SGLT2 inhibitor in the past and experienced multiple urinary tract infections. And in terms of her current medications, she's taking insulin clargine 16 units daily and insulin Lyspro 5 units with each meal three times a day. This is her AGP report, so she is utilizing intermittently scanned CGM. And we can see that she's spending 78% time in range, 17% between 108 and 250, and another 4% over 250. So in total, 21% above 180, and then 1% below 70. Her glucose variability is acceptable at 32.4%. And actually, her estimated A1C is indicated by our GMI is 6.8%. So even lower than her last lab, A1C. And so really, she's meeting the goals. It would be nice to have a little bit more data because we have 68% based on scanning, usually we aim for 70% or more. But when we look at this, overall, we see that she's meeting her goals. So it might be easy to say, well, maybe we should just let this patient continue on because overall, she's meeting the glucose targets. However, when we go back and look at our complication-centric algorithms, both through ADA and through ACE, we see that for people that have a cardiovascular disease, we want to utilize therapies like GLP-1 receptor agonists and or SGLT2 inhibitors. In this case, she did not tolerate the SGLT2 inhibitor. However, she is not on a GLP-1 receptor agonist. Also, our guidelines advocate that really the first injectable should be a GLP-1 receptor agonist. So we want to ask, why is she not on it? And could this be a viable therapy for her? The other consideration is her weight, her BMI is elevated, she has obesity. So she would clearly benefit from the weight loss from a GLP-1 receptor agonist. So we can initiate a GLP-1 receptor agonist. In this case, we went with semaglutide. We start with the lowest dose, that 0.25 milligrams weekly. And then we can titrate after four weeks to 0.5 milligrams, and then another four weeks to one. And then we have the option after another four weeks to go up to the max dose for diabetes, which is 2 milligrams weekly. But the question becomes, well, what do you do with her other medications when you go ahead and add this? Well, we can learn from a recent study called the Transition T2D Study. This was a prospective randomized control trial that took people that were well controlled on basal bolus insulin and started a GLP-1 receptor agonist. In this trial, they actually stopped the mealtime insulin and just incorporated a correction scale. If glucose was over 150, patients could take some mealtime insulin. And so this is a strategy that we can utilize. Also, going back to our insulin algorithms, if a person experiences hypoglycemia, we can decrease insulin by 10 to 20%. Those pre-meal insulin doses or if it's fasting hypoglycemia, the long-acting insulin. So this is the profile now six months later. Semaglutide has been titrated up to the maximum dose for diabetes of 2 milligrams weekly. Initially, the mealtime insulin was stopped. But over time, as semaglutide was increased, the long-acting insulin was also decreased to the point where it was completely stopped. Now, of course, some of this was the effect from the medication. But also, the patient reported making lifestyle changes based on utilization of the CGM and seeing how different foods impacted her glucose levels. So she was able to make healthier choices and also felt safe to incorporate more physical activity without experiencing hypoglycemia. In total, she experienced a 22-pound weight loss and reports that this has been a total game changer. And when we look at our AGP report, she's now actually 96% in target range, very low glucose variability. That curve looks almost completely in that 70 to 180. It's flat, narrow in range, and her estimated A1C based on this data is 6.3%. Some key takeaways from this section is that glucose targets should be individualized. And some of those factors we take into consideration are things like the risk of hypoglycemia, life expectancy, different comorbidities, and a person's support and system and resources. It's important to identify and optimize medications that can help preserve organs like the kidneys and the heart and reduce cardiovascular risk. And this especially includes use of the GLP-1 receptor agonist and SGLT2 inhibitors. Some therapies, unfortunately, have higher medication costs. However, there are several cost savings programs that can improve access. And when we think about it, by improving cardiovascular risk and reducing diabetes complications, this actually leads to long-term cost savings, like reduction in hospitalizations. And finally, when it comes to diabetes technology, continuous glucose monitoring has a wide variety of uses. It can really help with behavior modifications, promoting healthy eating, physical activity, and it also can help with dose titration and can support deprescribing medications when indicated.

Diana Isaacs

intensifying diabetes treatment

glycemic targets

medication choices

Continuous Glucose Monitoring

CGM

cost considerations

American Diabetes Association