This program is supported in part by an educational grant from Lilly. Welcome everyone to Beyond the Basics, Unraveling Challenging Type 2 Diabetes Cases. I'm Dr. Eden Miller. Thank you so much for joining us today. We are going to have an amazing panel discussion with three clinical faculty members exploring the key considerations related to diabetes management. We're also going to have a question and answer segment, and we will all be broken out into specific groups to talk about an in-depth clinical case study, one that's challenging, one that's going to stretch our thought process and how to dive deep into the different portions of diabetes and those different cases that are out there. I'm Dr. Eden Miller. I am a CEO of Diabetes and Obesity Care in Bend, Oregon. I'm today's moderator, and here are our learning objectives. We're going to discuss the use of glucose-lowering medications for microvascular and macrovascular reduction. We're going to recognize agent-specific considerations as they relate to diabetes clinical course among currently available SGLT2 inhibitors, GLP-1 receptor agonists, and those dual GLP-GIP receptor agonists among other medications. We're also going to try to really identify strategies so we can remove those barriers to guideline-interactive therapy. I think that's one of the most challenging things that we do. Now don't forget to stay tuned. We have many upcoming ADA professional webinars. Be sure to register for those. We've got one coming up May 13th from 1 to 2 p.m. Eastern Standard Time looking at exercise impact on cardiovascular function from extracellular vesicles to adipose tissue remodeling. That's going to be a great one to go to. Webinars on demand as well. Remember to learn more or register and visit professionaldiabetes.org slash webinars. There's ones on diabetes retinopathy, hands-on webinars for insights and screening with prevention as well as organized team-based care for diabetes is primary. Now let's meet our faculty. Today's faculty are the esteemed Davida Kruger, close friend of mine, amazing individual who works at Henry Ford Health in Detroit. She lectures extensively throughout the United States. She has been co-investigator in numerous studies of intervention including the NIH-funded multi-center edict and accord trials. She serves as editor-in-chief on two ADA journals. In addition, she is board certified in primary care and advanced diabetes management. And then I would like to introduce, we have Dr. Richard Pratley. He serves as the Samuel E. Crockett chair in diabetes research. He's a senior investigator and diabetes program lead at the Adventist Health Translation Research Institute and medical director at the Advent Health Diabetes Institute in Orlando, Florida. He's adjunct professor of medicine with the John Hopkins University of Medicine. He's both been a writer of over 400 peer review articles. That's a lot. I don't think that's amazing that he's done that. And principal investigator as well with both the NIH and pharmaceutical companies sponsored trials. His current research interests include prevention of diabetes, improved care of the aging person with diabetes, as well as developing new drugs and insight to prevent diabetes and its complication, as well as understanding the fat cell and its role in diabetes. And then finally, we have Dr. Curtis Triplett, a professor of medicine in the division of diabetes at University of Texas Health at San Antonio and associate director of diabetes research center at the Texas Diabetes Institute, which is part of the University of Health Systems at San Antonio. He is extensively involved with diabetes and metabolism research, as well as educating and managing patients with an endocrinologist. He is currently an editor in chief as well as a diabetes spectrum and education focus peer reviewed, published by the ADA. Welcome everyone. Thanks so much for joining us now with all about housekeeping out of the way, we want to dive right in. We want to go into the panel discussion and we have several different deep questions that we're going to be spreading around our faculty to try and get their insights in. And we're going to start with our first one, looking at the micro vascular and macro vascular risks. And I'd like to tee this up first to Curtis to say, can you give us a little bit about discussing the use of medication specifically for both micro vascular and macro vascular reduction? Sure. My, my pleasure. So I, I think a couple of things to remember is that, you know, there was that time, not more than a couple of decades ago where we, we were struggling within the community to convince people that glucose lowering lowered the risk of micro vascular complications. But then some of the other trials came out, such as the DCCT trial for type one diabetes. And we've had some of the newer type two trials, such as UK PDS come out. And so I think that's kind of died down a little bit as far as that. And I think what we in general understand is that glucose lowering has an effect on lowering the risk of micro vascular complications, eye, nerve and kidney disease and diabetes. So I think we're, we're, even though the medications used in those may be, may be metformin, it's a funny reason insulin. We kind of use A1C lowering as a surrogate marker to show a micro vascular risk. That is not true for macro vascular. So macro vascular risk is quite clear. We have clear definitive outcomes. We, we know that we wanted to either lower cardiovascular risk through a heart failure or MI or stroke or things like that. And those, and those outcomes really have switched and that's a paradigm shifting in the last few years. Of course, as we all remember, originally these drugs were being looked at just for safety. So what was happening is that we were afraid that some of these drugs were actually causing a heart disease, heart attacks, strokes, some of the thiazolidine diomes. And so the FDA required that these cardiovascular outcome trials be done. But at that point we actually started to find benefit with some of the classes such as SGLT2 inhibitors and GLP-1 receptor agonists. Yeah, it really goes to show that maybe we are still glucocentric, but we're really trying to go beyond glycemia, right? For sure. Yeah. Glycemic control is, is there for micro vascular complications, but it has, you have to have very long macro vascular, very long glucose control for macro vascular risk reduction. And that, that was clearly shown in advanced accord and VADT that in those kinds of patients who have cardiovascular disease, but you treat them for two, three, four years with better glycemic control, it doesn't seem to improve their cardiovascular outcomes. Yeah. I often say to the young residents, when you choose an agent with diabetes, what else are you doing for me? Like what is the other things? You know, with that, you know, Dr. Pratley, let's, let's go to that next question because, you know, we all know standards of care. We know guideline based medicine, you know, but there, you know, how do you individualize it? Let's go to our next question here. You know, how do those guideline recommendations tailor the choice that you have when you're looking at taking this all into account? Yeah. So I think, thanks for that question, Eden, that this is one of the challenges that we have in diabetes management at the moment. I say that it's kind of like the best of times, it's also the worst of times, it's the best of times because we have so many treatment options that are available for people. But that also makes it one of the worst of times because like, how do we choose from among all these options? What are the best choices for individuals sitting before us? Now the guidelines do help us in some respect in that they give very clear pathways for people with certain comorbidities. So patients with myocardial infarction, evidence of atherosclerotic vascular disease or high risk, those people should either get a GLP-1 receptor agonist or an SGLT2 inhibitor, preferably the GLP-1 receptor agonist with a proven cardiovascular benefit. Patients as Curtis mentioned with either heart failure or with chronic kidney disease should start off with an SGLT2 inhibitor. And the reason for that, of course, is the evidence that these medications help to reduce risk and progression of disease. Beyond that, then we also have other comorbid conditions like obesity. For most of our patients, this is an issue that we need to manage coincidentally with the diabetes. And here where the GLP-1 receptor agonist and to a certain extent the SGLT2 inhibitors come in handy as well. So I think that the guidelines help us by giving us certain categories of patients where certain drugs are preferred. Now that still is pretty broad. And so what we need to do is take a look at the patient in front of us. And frequently what we see is cardiovascular disease plus heart failure, plus maybe some chronic kidney disease. So what do we do in a patient like that? Well, then we have to make the best choice that's not informed by clinical trials. There aren't any trials in which GLP-1 receptor agonists have been combined with SGLT2 inhibitors. We think that they work through different mechanisms. So that patient might best be served with a combination therapy, for example. The other part of tailoring choice, though, is what is the patient's value? What are they looking for in treatments? We can talk all we want about long-term risk for cardiovascular disease, but we have to have the patient on board for them to really pick up the prescription and take the medication. So the other part of tailoring is understanding the patient values, understanding what they're trying to accomplish. And it may be that we can accomplish multiple outcomes or multiple desires at once. We might want to lower their cardiovascular risk with a GLP-1 receptor agonist. They may be most interested in lowering their weight and their A1c, for example. But fortunately, we can bring those two together. So that's the kind of discussion that makes diabetes management still interesting. You know, and we had a question pop up that I think this is a really good time to kind of answer as well. But it says, hey, would you go ahead if somebody had these comorbidities, had type 2 diabetes, had a high BMI, maybe had cardiovascular or not, would you go straight to a GLP-1? And I think the answer is yes, absolutely. It's patient-driven, it's patient-centric, because we're trying to address all of the multi-needs that they have on those different levels. So Eden, the only clarification I would make on that is I think everyone in this panel would agree that you meet the patient and the first thing you want to do is use a GLP-1, however, or GIP, GLP-1, whichever. The problem is insurance. And I want to make sure the audience understands that most insurance today still require that the patient be on metformin, then request it. So you want to maximize your metformin for insurance purposes, and then quickly bring on the GLP-1. I think that's really important to know. Yeah, it's where the science and the payer meet. It's still a challenge, and I still think that there are barriers. But I think one thing to know is it's not that you can't use that. It's just how are you navigating this thing? And so, Curtis, I'm going to toss it back to you because the next question is a little bit more diving down a little bit deeper. You talked about the macrovascular, but how do glucose-lowering medications, how do these particular ones reduce that macrovascular complications with diabetes? Well, to say that we know exactly how these classes do that, I think would be incorrect. But we do know, we know a lot about these classes as far as mechanism of action. And I feel a little funny doing this because Dr. Prowley is an expert in this area for sure. But I'm going to say it anyway. I'm going to do it anyway, Dr. Prowley. So, you know, for GLP-1 receptor agonists, I mean, one of the things is that they, I really call them vascular health drugs. They're very good at decreasing inflammation, improving endothelial dysfunction. They help with glucose uptake, obviously, and that's true not only in, for example, skeletal muscle, but also probably in the heart. We know that they seem to have in the kidney a natriuretic effect and that if your blood pressure is high, they can lower the blood pressure. And then, you know, we're not even talking about the indirect effects such as helping the patient lose weight eventually, lowering triglycerides and LDL, those kinds of things, and even lowering liver fat. SCLT-2s are the same kind of story. There's a lot of different mechanisms. We know that at the core of this drug, they simply make you pee out sugar. And I think a lot of people missed, in fact, I don't know anyone who really thought that these drugs are going to be spectacular drugs to lower renal or cardiovascular disease, but the answer is we're starting to learn all these really interesting mechanisms. And one of them is really offloading the proximal tubule. So by offloading the proximal tubule of all that glucose load and letting that glucose go down the tubule farther and be peed out, seems like that may help with EGFR protection, so through tubular glomerular feedback, improve renal function. We know it lowers uric acid. I'm not saying that that is the way that it lowers cardiovascular risk. Because some outcome trials have not been positive for lowering uric acid, but it may contribute in some way to inflammation reduction that we see. They do lower blood pressure. They are glucodiuretic drugs. They do improve vascular health and decrease endothelial dysfunction. And they also increase erythropoietin, which probably helps with some oxygenation features within the body. And then last but not least, the one that we're studying here in San Antonio quite a bit is ketones. So ketones, it increases ketones, which, of course, could be the risk of euglycemic decay, but also is certainly a super fuel kind of for tissues, including the heart, which may help to reduce cardiovascular disease. So they're very complex. We don't know the mixture of which one does which and how it does it. I think, as Dr. Padley said, the mechanisms are different, though. So we really think, you know, that there is a possibility for a combination long term. You know, Richard, I think Curtis did a pretty good job, didn't he, of summarizing that. But why don't you add your final comments and then take us into some of the microvascular, the kind of the how and the why and that kind of thing in microvascular. Yeah, so I think it is so interesting. There are GLP-1 receptors all over the body, including in the brain. And these drugs have pleiotropic effects, many of which have been documented, not in animal studies, fewer in humans. In contrast, the SGLT-2 inhibitors, fairly focused effects on the kidney. The SGLT-2 transport is not expressed much beyond there. And yet both of these drugs have these somewhat overlapping effects, distinct effects in many cases, and beneficial effects. And what we're really doing is making up stories about how they work beneficially. We do think that reducing inflammation is one of the key benefits of the GLP-1 receptor agonist. The newest data suggests that this may even be centrally mediated, which just blows my mind. And then ketone production and substrate shifting may be very important for the heart and for the kidney with the SGLT-2 inhibitors. But it's really hard to figure out mechanisms. And I think it's fun to think about those things. But we also have to keep in mind what the real outcomes we're trying to prevent are. So it's heart disease, it's kidney disease, and it's lives. And we can do that with these medications. In terms of the microvascular complications, as Kurt has already mentioned, a lot of these are directly related to glycemia. And our studies have been fairly consistent that if you lower glucose levels by any method, you can reduce the risk of microvascular complications. Now, traditionally, nephropathy was one of the microvascular complications. But we know the SGLT-2 inhibitors are effective at markedly reducing risk of progression of nephropathy. There's also emerging data that GLP-1 receptor agonists may be beneficial in this regard. So there's meta-analysis that we were part of that suggested that a composite kidney endpoint was produced with GLP-1 receptor agonists. And people will want to stay tuned for the results of the FLOW study, which was a study of semaglutide that I co-chaired that will be releasing results in May at the end of this month at the European Renal Association meeting. So we're very excited about those results as well. So just like with the macrovascular complications, we're learning more about how these drugs might have beneficial effects on microvascular complications as well as other indications. Well, that's just great. I'll tell you, all things are pointing towards these primary and secondary benefits. I think that's why we're spending this very distilled down time to look at it. But, you know, Devita, take us to the clinical course. I want to look specifically at the person who is utilizing GLP-1 receptor agonist. Kind of give us an idea of how they may differ from other therapies when you're specifically choosing a GLP-1 for an individual. So, you know, I think Rich started off with the best comment that it's the best of times. This is the worst of times. And I always say that it is the best time to have diabetes. It's not a good idea to have it, but it is about the best time ever to have diabetes. Because when I first started more than 40 years ago, all we had was sulfonylureas and mixed beef pork insulin for people who had type 2 diabetes. So now in walks these amazing drugs, GLP-1 and GLP-1 GIs and SGLT2 inhibitors. And the difference is that we were causing, with other medications, lots of weight gain, lots of hypoglycemia. And if you think about the patient who has type 2 diabetes, most of them are going to be obese, if not all of them are overweight. And the last thing they want is to have a deal with weight gain. And the thing that they're most upset about usually for type 2 diabetes is hypoglycemia and weight gain. And I can guarantee you if you give a medication that causes hypoglycemia, that that patient will eat up to that type of day, or they will omit their medications. And the family members will be standing there at two o'clock every day with a meal if that's when they had the hypoglycemia for the rest of their lives. So if we can provide a medication like either the GLP-1s or the SGLT2 inhibitors that do not cause hypoglycemia, they're glucose dependent. So when the blood sugar is elevated, they take care of the glucose when the glucose is normalized, they shut off the glucose lowering mechanism, hence in themselves, they do not cause hypoglycemia. And the GLP-1 category has a greater weight reduction, although then the SGLT2 inhibitors, but both of them have weight reduction and not weight gain. And typically, if I lower an A1c by 1% without those medications, I'm looking at 10 pound weight gain, I've lost that patient's attention. There's no way I'm barely five feet tall, you put 10 pounds in me, I promise you I'm not going to take your medications. Your fun size, Davida, your fun size. So they lower the blood sugars, they don't cause hypoglycemia, they have a weight reduction. And now lo and behold, you know, we're all making history with these medications that have a cardiovascular benefit or renal benefit. What are the things that we're worried about? You know, I always tell my patients, the greatest risk in your life is going to be cardiovascular disease. They have elevated lipids, they have hypertension, not only will these now we're not going to not give them, you know, lipid lowering medications, we're not going to not give them blood pressure lowering medications, that's a must. But if I can give them one of these medications, or two of them combined as my first drug on right after metformin, because I have to look at all the benefits I can provide for the patient. Now, the education has to go with that. And the education is that, guess what, GLP-1, GLP-1-GFP has caused some nausea that's drug related in terms of the dosing. And we have to talk to them about portion sizes. But it does work on the central and the brain and turns off that sense of fullness and delays gastric empty and all those good things. So education has to come with it. So the patient is comfortable with what the drug is what it isn't. And also so we can help them with changing in food activities and intake. You know, just jump in here and expand real quickly. You know, I love what you said, Davida, you and I have both been around long enough to remember when we used to say this is critical, you need to lose weight to manage your diabetes, and then we will put them on insulin, or sulfonylureas. And the way we go up, right, we're now in a position where we can help them with this journey, which has been a problem for decades, and which continues to be a problem. And I look upon the GLP-1 receptor, I guess, and SGLT2 inhibitors as a way to help facilitate patients behavioral change. So yes, they'll cause some weight loss independently. And that's good. But I think they also help people become motivated helps them jumpstart those kind of behavioral changes that are necessary. So a healthier diet, making it easier for people to exercise. So I take advantage of the opportunity of initiating one of these drugs to really get people on a good lifestyle path. In addition, I think that's really critically important for people being successful on these medications and just being successful in general and managing multiple conditions. I think you're right. Physical activity is important. Diabetes education, diabetes, self management, education, seeing a dietician, all of those things have to occur to support we don't just give the drug and say, Hey, lay back and see what happens. There's so much that goes with it that we have to remember and I have to throw in continuous glucose monitoring as well. Absolutely. I think of these as like you're learning to ride a bike and you need training wheels. You don't lean on your training wheels. Your training wheels are there to help you learn how to ride a bike. You still got to pedal. You still got to do all these things. Hey, Curtis, wrap this particular section up with your view from the pharmacology standpoint is, are there any specific things regarding these agents where they're an SGLT2, a GLP-1 or a dual that you're going to say, Hey, I want to make sure that my patient understands that there's these agent specific considerations. What are your kind of top line takeaways with those? Well, I mean, I think most SGLT2s are kind of similar to each other, though. They don't all have the same outcomes. So I think, you know, one of the things about SGLT2s are oral, they're all once daily. They all help you pee out glucose. There are some differences in outcomes. Some of the more recent SGLT2s have not had positive outcomes. You know, we have to lean more on the empagliflozin, the dapagliflozin, and those kind of drugs in order to see some of the positive cardiovascular effects that we've seen. That's also true in GLP-1. So, I mean, if you look, we now have an oral GLP-1, which I think is wonderful. And, you know, when I first started, one of the first things people told us was, Oh, well, gosh, if that was just in an oral form, I think I'd take it. So now we have an oral GLP-1, which I think helps for a certain segment of the population. But now, all of a sudden, it doesn't seem like needles are a big deal, whereas before they were such a big deal. You know, I think it's wonderful that we have a difference in how you administer these drugs. So they're auto-injectors, many of them now, such as the tercepatides and the dulagutides. And these auto-injectors, I think, help people to be able to inject efficiently. On the other hand, you know, if you have someone who does a great job, a pen like a semaglutide pen is more titratable. So you can kind of look at the device and choose a GLP-1. Also, the fact that, you know, the old GLP-1s like Exenatide were twice a day. Then we went to once daily with drugs such as liraglutide. And now we're to weekly. And I'll tell you, there's a lot of companies coming out. They're probably going to be monthly for sure in the next probably several years. So I think it's possible that we have a drug here that could really help people. And I think, you know, there are differences between these classes. I think, you know, as everyone has said, as Richard and Avita have said, you know, SGLT-2s appear to be superior for renal. I would say that at least evidence-based wise right now, I would put an SGLT-2 above a GLP-1 receptor agonist as far as evidence-based wise. We'll see long term what happens. I'd say that for heart failure too. Even though there is some evidence for GLP-1s helping heart failure, I think SGLT-2 has more robust data. And also, but then on the other side, I'd say such like a GLP-1 seems to have a little better robust data for prevention of strokes. So, you know, you look, you can look at the device. I think side effect wise, Davita clearly made the differentiation there between the two. You know, the SGLT-2 inhibitors are more about peeing out glucose and maybe a little hypotension. We had a few patients like that at the beginning who didn't have the blood pressure medicine adjusted, who had a little hypotension, especially in South Texas heat that we have sometimes. A little bit of volume depletion with it as well, eh? Sure, right. And also a few yeast infections and things like that. So, side effect profile is different. As Davita had said, the GLP-1s are about nausea and vomiting and diarrhea and things like that. So, I think overall there are some differences and, you know, you have to pick and choose based on your patient which ones you think would be most pertinent to them. And I always say the same thing, how are you going to know? You have to ask. So. So, our final just area before we're going to jump into our small groups is can, you know, share kind of a top of line of how we overcome barriers to guideline in therapy. I'll share one of mine. I tend to dictate in my note that the guidelines are indicating that we do these particular medications. There is actually a great module through the ADA that Lucia Novak and I did about called Pharmacy Hacks. So, I understand that those are all of those challenges, but I'd like to go to the faculty before we jump into our breakout room. So, kind of your top of line, what may be one of the things you do to try and identify and remove those barriers? Yeah, I think that the most important thing is to make sure what you need, you understand what's required to get it, if that makes sense, and that you document that in your chart. So, these are standards of care. I'm going to follow the guidelines and I'm going to put this in my note and I'm going to say, because the guidelines say this, this is what I'm going to be doing and these are the medications I need to be using. I think that it's just really important to understand what the guidelines say and then think about how to incorporate that into my practice. I think that helps get you off on the right step, you know, when you're trying to get the pre-authorization for some of these medications. Sometimes that's not enough, but it seems like people don't read the notes or don't agree. And so, I also have form letters that I customize for patients that include, you know, the information like the patient has a history of an acute MI, you know, a year ago. The ADA guidelines referenced recommend a GLP-1 receptor agonist. I am prescribing this GLP-1 receptor agonist with a proven benefit for reducing cardiovascular disease. I hope you'll see my side of it. I'm nice, but I use, you know, the guidelines to help make the case for individual patients along with their history, along with their medications, you know, and I think that's one of the strategies that is effective. It's not always effective. I mean, I just got out of the clinic and I was fighting to get one of my patients on something that she really benefits from. So, any other parting thoughts regarding barriers before we jump into our live Q&A? So, we've had some great questions coming, a few of which that I noticed faculty did a great job of incorporating in. You know, we did receive a question about new patients who have a very high BMI, who are struggling with overcoming, you know, their diabetes challenge. Would you go straight to a GLP-1? I think many of us said, yeah, we would based on those guidelines, but again, insurance is that challenge. And I liked how Dr. Pratley says you create a case. I tend to usually say, you know, I'm hitting many things with this particular therapy and this would be the standards of care. But I did get one question surrounding GLP-1s and we'll kind of open it up to the group of, you know, have you seen issues with chronic kidney disease and GLP-1s causing GFR to go down? Well, I know kind of what I'm thinking, but I'd like to see what the group thinks. So, maybe I'll field that one. And what we know from the GLP-1 cardiovascular outcome trials and longer trials is that if patients have nausea, vomiting, become dehydrated, it can precipitate kidney injury. And that's a warning that's in the label. However, if you look across large numbers of patients in trials, what you see are fewer cases of AKI in patients who are treated with GLP-1 receptor agonists, and you see improvements in things like GFR, albuminuria over the long term. So, I think that you have to take each patient individually, make sure that they're hydrated, make sure that they don't run into problems with dehydration and become pre-renal, but also don't be afraid of them in chronic kidney disease. As I said, we have some pretty compelling data that will be presented later this month that suggests GLP-1 receptor agonists are, in fact, the fourth pillar for the treatment of CKD and type 2 diabetes. Nice. I think also is just to remind us as our group, the GFR is a, is kind of a point of care, like flow rate. It can change. It can change by a lot of different things. If you're dehydrated, like you said, if you're taking other medications, but I think that the data we've seen is that these are safe. They are actually eliminated as an intact molecule through the gut. They're not metabolized through the kidney. So really when you're looking at flow rate with the kidney, it's how you keep the kidney happy and hydrated. Now, another comment came up about retinopathy. You know, we know that in some of the GLP-1s there are retinopathy type of issues. You know, I know what we do is, you know, we never stopped screening for retinopathy and treating it. Any top of line in terms of if you use it in those individuals with retinopathy, or if you see retinopathy, how does that change your direction? What do you do differently? I'll start. So I think when you look at the studies, it's important to understand that it was in just the cardiovascular studies. And those studies were individuals who already had some retinopathy or some marked retinopathy. So I think it's really important to understand that that didn't occur in any of the other studies. That's not to minimize it by any means. And if you have someone with marked retinopathy, any therapy you use, if you go too rapidly, you have the risk of a temporary worsening of the retinopathy. So if I chose insulin over a GLP-1, I'm still going to have to go slow and low with the therapy. So in my own clinical practice, what I try to do is I always want to know what the status of their eye disease is, because that's very important. And if it's marked, we work with the ophthalmologist. But otherwise, if we're concerned, we might not use the increase every four weeks, we might start at the lower dose, we might keep that patient there for eight weeks, then go to the next one, and just try to lower the A1c slower, because we really believe that a lot of that has to do with how rapidly we correct the A1c. We saw that in the DCCT, and we had to slow down lowering the A1c. We see that in pregnancy, which is why we often send those women for eye exams every trimester. But I think you still have to lower the A1c, you just go slower so that the A1c is not lowered as rapidly. Hey, Curtis, there's a couple questions here regarding kind of GLP-1s. And you know, one was what about talking about GLP-1s and the risk of cancer. And then the other is looking at this gastroparesis, there's a lot of buzz around it, I like to use the word gastric slowing, because you know, gastroparesis is an autonomic neurological event. And so talk to us a little bit, some of the questions are, do you stop it? What do you do? Do you screen for it? You know, tell us a little bit about those two complications. Well, first of all, I think there is one cancer that these drugs have been associated with, and it's, it is real, and I think you need to know about it. That's medullary thyroid carcinoma. So the drugs, at least in rat models or rodent models, showed at typical doses that there might be a higher risk of this particular cancer. So those with MEN2 or with GLP-1s, those with MEN2 or a history of this particular cancer should not be using this class of drugs. But I also want to always mention here is that, you know, in endocrinology, the ones that we see the most are those who have had papillary or follicular thyroid cancer. And that has nothing to do with this kind of cancer that we're speaking of, even though they're both from the thyroid, embryologically, they're different. So it's important to remember that that is not a contraindication to use of these drugs, because that is the one in practice you'll see the most common. Other than that, it has not been associated with other risks of like pancreatic cancers when I hear thrown around. Remember, there was a person out on the West Coast that did some bad science and came up with some cadaver stuff on some glucagon and things like that. And we have to remember that good science, that was thrown out. A lot of that was withdrawn. And there has been no association with pancreatic or anything like that. There is an association with slowing a gastric emptying, we know that. Over time, GLP-1s do cause a tachyphylaxis to that effect. That's why GI side effects go away. The latest craze seems to be that people are claiming that they go off the drug and this gastroparesis remains. I find that hard, not impossible, but hard to believe. But it's quite clear that these drugs slow down GI transit. We have to accommodate for that. And also, we have to, you know, that's come out with even recommendations from the anesthesia folks saying we should stop the drug a week before elective surgeries and things like that to try to minimize this GERD effect and things like that. I'm not sure it's going to help that much, but it's not going to hurt. So, we certainly can implement that for patients to see if we might be able to help our anesthesia partners as they get some of these surgeries. One of the unanticipated benefits of these cardiovascular outcome trials is that we have tens of thousands of patients on these drugs for up to five years or so. And what this has done besides telling us about the cardiovascular benefits of these drugs has given us a window into some of the safety programs, including things like pancreatic cancer, so not increased in these trials. Pancreatitis, surprisingly, even though there's a warning in the label, in meta-analyses of the GLP-1 receptor agonists, not increased in these trials. And medullary thyroid cancer, a very rare form of thyroid cancer, has happened in these trials. I'm aware of one case in a placebo-treated patient. This has been an issue that just, you know, won't go away because of the animal's signal. What I do is, you know, I talk to my patients because they all read the package inserts. I do this prospectively, and I say, you know, I've done a very careful physical exam, which I generally do. I see you don't have enlarged ears or a long tail. I believe this drug will be safe. Also, by the way, GLP-1 receptors aren't present in the cells of these tissues. So yes, for sure, people with MENTU, family history, any family history of medullary thyroid carcinoma, we should avoid the drugs. Other than that, I, you know, don't make much of the cancer issue. You know, we've got really, really great questions coming. We really only have time for one, but I'm going to smoosh it all together because we see it. And so I'm going to throw it out there to the group. So the first is a little bit, I'll answer first about SGLT2s and GLP-1s and type 1s. There are some studies, there are no indications yet. It's kind of, you know, type 1 diabetes is a challenging one. I think especially with SGLT2s, you got to worry about potentially of insulin deficiency or ketosis. But the question that keeps coming up a lot are these, what we call euglycemic decay. I don't like to call it euglycemic. I call it lower threshold DKA because it's really a relative term because when you dump sugar with an SGLT2, you hide the glucose, you hide kind of the true glucose. But there are a lot of individuals asking about, let's say you see a person on an SGLT2 and they develop DKA type symptoms. The questions are, do you screen for it? Do you not treat it? You know, we all have our own styles of how to do it, but I get this thread of, you know, you're on an SGLT2 and you need to get DKA, what to do, how to prevent it and how to address it. Any thoughts? So I can take this and then, you know, maybe Debita can put a cup or two cents worth in. I know that Curtis has also studied this a little bit. In the studies that we were part of, it was the minority of patients put on an SGLT2 inhibitor that actually developed ketosis and a very small number developed DKA or euglycemic ketoacidosis. So ketone levels do seem to be helpful in predicting and people that I would consider putting on an SGLT2 inhibitor with type 1 diabetes, I would definitely recommend ketone monitoring, particularly if they were not feeling well, if they didn't eat, if somehow they skipped insulin dosing or had a pump failure. It's critically important in those situations because the SGLT2 could enhance that risk. Now, one of the interesting developments that I think may allow more people with type 1 diabetes to go on these medications is that within a year or two, we'll have a continuous ketone monitor that is like a continuous glucose monitor, but will provide thresholds for patients in which they might want to introduce some risk mitigation to prevent ketones from forming or ketoacidosis. So, you know, diabetes is so interesting because it's always evolving and this is going to be one of the newest evolutions in technology that I'm really looking forward to. We're going to learn a lot about ketosis and ketones. I do not think we even know for sure. So any other thoughts, Davida, before we go into our breakout? Yeah, the only other comment I would make, because we do, when we're using the SGLT2 inhibitor in type 2 diabetes, we do talk about the risk of decay, even though it's more of an issue for type 1 diabetes. But I think if I see it, when I see it, I do also like to check to make sure I'm actually looking at type 2 diabetes, not type 1. And I probably would run some GAD antibodies or other studies to be sure that person, that's not to say people with type 2 diabetes don't have DKA or hyperhidrostates, but it just makes me think twice when I see that. Or they may be type 2, but they may have very low insulin reserve left at that point. So those are just a little few caveats of safety and making sure the patient knows what it looks like and they respond quickly so they don't get into trouble. Yeah, I would agree. I don't screen, but you definitely, if you look at somebody in front of you and you start scratching your head, looking at their phenotype, looking at their variability, looking at things up and down, check it out, you know, but there are those, what we call lean phenotypes, ketosis prone, insulin deficient type 2s, you know, they're out there. Okay. So now what we're going to be doing kind of as a collective herd is we're going to be breaking out into four different groups. You will be automatically transferred and we're going to be going through a case. So now we are going to briefly go through our four cases. We're going to start with case number one, which was Davida Krueger's. All right, and I have Will Chapman that's going to help me. This is our newer diagnosed individual. He had type 2 diabetes two years ago and referred for assistance in managing his diabetes, 56 years old, 5'10", his BMI is 33, fasting blood sugar is 276. When he was diagnosed two years ago, his A1c was 7.1 or 7.6, and now it's 8.2. He does have a history of hypertension, elevated lipids. He's on metformin, that should say a thousand milligrams in the morning and 500 in the evening, lisinopril, 40 milligrams for hypertension and 40 milligrams of ruvastatin for his lipids. And take it away, Will. Yes, so he's maxed out on the metformin, therefore we're going to recommend a GLP-1, whichever the insurance company will cover, as well as refer him to MNT and or DSMT group classes for nutritional counseling, recommend increased physical activity, and add a continuous glucose monitor so that he's able to see the feedback of the effect of both the medication and also of the additional education. We focus really hard on the fact that the patient does need education and has never gotten it, and that that will be the backbone of everything he does. We also said we prefer a GLP-1 that has a cardiovascular indication, but you know we we do follow regulations and we will document in the chart that the patient does have is high risk for cardiovascular disease. Nice job, Will. Thank you so much. Yes, ma'am. Thank you. All right, we'll go on to case two, which I am not Ann Peters. I am substituting for Ann Peters, but we had a very interesting case. We had Alma, who is 32. She developed type 2 diabetes after having gestational diabetes. She was employed as a seasonal worker. She manages a lot of stress due to social determiners of health, but I would like to add that she had gestational diabetes, but then she actually presented in DKA and then was diagnosed with diabetes and subsequently recovered, but was placed on metformin, a thousand milligrams twice a day, glipizide 20 milligrams twice a day. Due to her age and her comorbidities, we have a glucose target, an A1C target of less than seven, but she presents to the clinic. She is in an overweight condition, an A1C at 10.7 and an EGFR of 90. So we didn't get to our group of who would like to present, of how we determine what kind of person with diabetes she was, what diagnosis, and then our next steps that we did to manage this. Who would like to with my group? This is Yolanda. I can, I can, I can try. Thank you, Yolanda. You're the best. Thank you. We decided to test, just to rule out, we wanted to make sure she was type 2 diagnosis. So we talk about testing for antibodies, mainly the C-peptide and the GAD and other, other few. We said that if everything is negative, she was most likely type 2. We also discussed the MODY because she had a strong history of type 2, mostly in her family. That wasn't an option for this case. And then for treatment, GLP-1 was the first option. She was put on, on GLP-1 semaglutide. She also got a CGM. And with time, the results came out, time in range with a few weeks, I guess, it was like 20%. Her, her blood sugars were really even. How do we call this? Variability. She had a very low variability. Her numbers were tight and high on CGM. So after that, looking at that C-peptide, I believe that the result was 3.6. So we, we, we knew that she wasn't producing that much insulin. So Eden asked us, what will be the next step of having a timing range of 20%? What will benefit this patient? So because her variability was very even, the group decided basal, basal insulin. And we decided to start her on, as usual, 10 units titrate every two to three days, 10% or two units. And within a few months, she came back and on her CGM results, timing range was 94. So that was a good treatment for her. Thank you so much, Yolanda. It's a very interesting case because it had a little DKA, a little diagnosis of what type of diabetes she was. We placed her on the standards of care GLP-1, but it wasn't everything to try and control her glycemia as her levels were still tight and high on CGM. She needed that basal insulin, but just that addition of that small amount of basal insulin got her into near a hundred percent of her time and target range, which was great. Thank you so much, Yolanda. We'll go to case study three, Dr. Pratley. Sorry, had to take myself off mute. So this is Bill. He's a 66 year old gentleman, history of type 2 diabetes, hypertension, hypercholesterolemia. On exam, his blood pressure is 134 over 84. BMI was 32. A1c was 7.7. LDL was 104. His creatinine was 1.9. EGFR is calculated to be 48. Urine albumin to creatinine ratio was 200. And the medications he was on were metformin, 1000 mg BID, citigliptin, 100 mg a day, simvastatin, 20 mg a day, lisinopril, 20 mg a day, and a baby aspirin. We had some great discussions around this gentleman. He's got a number of issues that we thought needed to be addressed. I'm going to ask Dr. Wilson to summarize because he really got on top of all of the issues, not just the diabetes management issues that I think are key in this patient. Dr. Wilson? So, when we take a look at this patient, one of the things that stands out, that's clearly apparent is the fact that he has chronic kidney disease. He basically has a 3A or possibly a 3B CKD, and he also has albuminuria. So, he's at high risk for progression of chronic kidney disease, and he meets the criteria for the ADAPA-CKD trial. In terms of approaching these patients, I think an excellent reference is the ADA-KD-GO consensus report. And what that suggests is you take a look at these patients and treat them with pillars of care, and the first pillar would be to improve their glycemic control. What was suggested in our group is the fact that this patient really should be on an SGLT2 inhibitor. We would have to remove some of the other medications, and possibly we might have to add later on a GLP-1 receptor agonist. The other issue to deal with is blood pressure, and we really need to maximize the dose of the ACE inhibitor in this situation. The patient should be up titrated to the maximum tolerated dose of an ACE inhibitor in this circumstance. And in addition to that, we should insist on exquisite blood pressure control. It should be clearly less than 130 over 80. Finally, I think that the other thing that we should consider in this particular patient is that he should really be on a high-intensity statin. There's a clear need to get his LDL down. It should be less than 70. If he has any evidence of atherosclerosis or prior MI, it even needs to be lower. So, we need to address this patient by using the pillars of care, and that includes glycemic control, blood pressure control, the use of a high-intensity statin. So, Dr. Eden, I want you to sign Dr. Wilson up to be a panel member for our next education intervention. I was thinking he was just one of our group, for sure. Thank you so much. That was quite a concise and well-thought-out response, and I love to hear that from us as our colleagues out there practicing. Thank you so much for that analysis. Great job. So, let's go on to case four, and that was Dr. Curtis Triplett. Yeah. So, we have John, who's 57, here for evaluation for his primary care doctor. He's had type 2 diabetes for the last seven years. He also has hypertension, dyslipidemia, and obesity. Right now, his blood pressure is 120 over 74, RR872. He's obese. A1c is above goal at 8.7%. Total cholesterol is 131. ALT was 57. His LDL was 49, HDL 31, triglycerides 256, and his EGFR is 56. Currently, he's taking metformin 502BID, Simva 40, Lisinopril 40 daily, hydrochlorothiazide 25 daily, and a baby aspirin, and then he takes a little ibuprofen now and then for some OA pain, and I believe it was Jennifer. Jennifer, at the bottom, there is a place to do a reaction. So, we discussed having possibly, there was no mention about whether or not he was doing blood glucose monitoring. So, inquiring about that, we determined he might be a good candidate for the GLP medications. We wanted to know how does he deal with his nutrition, and what's his lifestyle like, because he does have a high, admitted to a high stress job, eating out for lunch every day and skipping breakfast. We want to know what is his stress management like? What is his quality of sleep like? How does he rest? We want to reassess lipid-lowering medications and increased monitoring of the retinopathy, and possibly cardio follow-up given his family history. Very good. Okay. So, we didn't come to an absolute consensus on which medication we should use. There was teetering back and forth between an SGLT2 and a GLP1 for obvious reasons, because that's the way the case was set up, to teeter back and forth between choices. Well, thank you so much. As you can see that these cases are very specific in how we look at the individual. We're taking the individual, we're determining what this person needs from us. We're trying to make their therapy very specific for them while we're following the standards of care, while we're trying to figure out what type of diabetes this individual has. And so, we thank you so much for your participation. We do have some more time for Q&A, question and answer. What I've done is I've taken some of the questions that we've already answered, and kind of eliminated those and distilled them down. And I'll be trying to get to as many as we can over the next few minutes. And then we will make sure that we try to get to all of them. If you have additional burning questions, please submit them in that Q&A area. We want this to be meaningful. I do see this one, Dr. Pratley, I'm going to send it to you. And there's a few. I'm going to have you talk about the cardiovascular risk reduction of metformin. What kind of dose? I saw some questions of somebody who's on 15, shouldn't we go to 2000? Won't that make all the difference in the world? So, if you can address those two things. Sure. So, what we know about metformin and cardiovascular risk is largely from observational studies. There's not been a prospective study of metformin in reducing cardiovascular risk, nor will there ever be. What we know is that this seems to be at least safe. And compared to some other medications in these observational studies, there seems to be reduced risk for cardiovascular events. But again, this is not the same level of evidence that we get from a prospective, randomized, controlled trial. Nevertheless, I think it's part of the foundational therapy for patients with diabetes, and I think it's perfectly safe in patients with cardiovascular disease. So we shouldn't be afraid of using it. I don't look upon it as a substitute for medications with a proven benefit. In terms of the dose, what we know about metformin is that you get the most bang for your buck when you're initiating and starting at lower doses. And then as you go to higher doses, there's a progressively smaller increase or decrease in the A1c. So you may or may not get a benefit going from 1,500 to 2,000 or from 2,000 to 2,500 a day. It's not unreasonable to try that, but I wouldn't also at the same time expect great outcomes in doing that. Well, thank you so much. That kind of helps us where to know and what to put in metformin. Okay, David, I got some two fun ones for you. You ready for this? I got the scandalous ones for you because I know you like that. That's scandalous. One of the questions was, is there even room for a DPP-4 anymore? And then the other one was surrounding switching Lantus to BID dosing. I know you have thoughts on that. And so those were two questions that we had that were a little different from this, but I think it gives us an idea of how do we navigate those other medications. So the answers are no and no. No and no. Let's start with the DPP-4 inhibitor. When they first came to market, we were pretty excited about them. The problem with the DPP-4 inhibitor is it has limited A1c lowering. They don't last for a whole lot of time. The benefit doesn't last for a whole lot of time and it's weight neutral. Now it doesn't have GI side effects, which is a real bonus. So perhaps if you had an elderly individual, and for me, elderly is like over 75 or 80. When I talk elderly, that's a personal comment. Thank you, Richard Ries. But I think that there's very limited value or use for the DPP-4 inhibitor. Now keep in mind, if a patient's on it and you're going to move to a GLP-1, you want to get rid of it because it's still in the same category. It doesn't cause hypoglycemia, weight neutral, and it doesn't have GI side effects, but it has little value. It's going to probably have the generic punch to it, then people will go to it, but I wouldn't use it. And then in terms of BID Lantus. So now that we have GLP-1s, you're going to start with a GLP-1. You're not going to use insulin, basal. Used to be, you know, meet the patient, give them basal insulin, meet the patient, give them basal insulin. Now we're saying hold the insulin until the A1c when you meet them is greater than 10% or greater than 9% and symptomatic. So you're going to already have them on GLP-1. The Lantus, the problem is, of course, Lantus is only probably about 21 to 22 hours, and there's a little bit of a gap in there. But if you're using a GLP-1 with that, you probably don't need it. Or if you're using a mealtime insulin, and if you're concerned, go to a longer acting basal insulin and, and breaking news too, we're going to have a once weekly come out probably in the next month or so. So I would avoid twice a day because of the onset peaks and durations that could get the patient into more problems with low blood sugar. Oh, thanks so much, Devita. Curtis, a couple questions. One regarding side effects about looking at GLP-1 versus dual incretins, the twinkertins, GLP-GIP. And then the other is, you know, when you add a GLP-1 or an SGLT-2 to an insulin basal already, what do you tend to do? So the first question, I'm a little confused. What, what was the question? Oh, so I'll make it straight up. Which one has more nausea, the twinkertins or the GLP-1? Oh, okay. Well, I, I think first of all, I mean, the, the, the dual actually has been shown to be pretty well tolerated. And I, and I think that, that was a little bit of surprise to us because of the fact that the, we thought, you know, more potency, more side effects. That's the way most of these drugs have kind of gone. But we didn't really see that. It didn't seem to be that way really with the terzepatide drug. So I think there is some room there to say that there could be a slight difference between the, the two as far as GI side effects. I, I do think there are differences, of course, in the other GLP-1s. It seems like the shorter acting may have slightly stronger effects. That just may be due to acute effect versus chronic effect. And also I think it, as most people have mentioned, I think it's about titration. So it's really, it's really about listening to the patient and titrating appropriately based on what the patient is telling you, not what the package insert tells you to do. So remember that the package insert is there to guide you, but the patient is there to tell you what to do. So I think that that's where we start with that. And then the second one was about. When you add an SGLT-2 or a GLP-1 to basal insulin already, what's your kind of, we all kind of have our little titration algorithm. Yeah. So I think if you're below, below eight, I, I back off on the, the basal insulin by 20% when they started GLP-1. I do not do the same for SGLT-2. And I'll tell you why. I think this is how you get yourself into trouble with the diabetic, you know, the euglycemic decay. When you look at the literature, I don't think, I haven't seen that these drugs are extremely insulin sparing, SGLT-2 inhibitors. And so I think the answer is that one, let the patient prove to you that they're going to go too low before you back off on the insulin. So I treat SGLT-2s differently than GLP-1s. If you're above eight, I keep GLP-1s, I keep the insulin at the same dose until again, they prove that A1C goes down low enough where I should lower the insulin. Thank you so much. I don't want to let you off the hook without a scandalous question. We got a question regarding compounded semaglutide. So the short answer is don't. You can't tell for sure the concentration. You know, what I heard is that, you know, there's been a flood of different reports on side effects. And a lot of those that are being reported actually are with a compounded semaglutide. It's coming from nefarious locations around the world to your pharmacy. And I just think that, you know, it's a very gray area how they actually even get it onto the market because of the shortage. But I think as a patient, I can understand the need to consider it. But the problem is that side effect wise, I just can't recommend it. I just can't as a pharmacist. Well, thank you so much. Devita, you wanted to comment about insulin titration? No, I want to comment on the GI side effects. I just want to say on the compounding is that that's not a negative on compounding pharmacies. We know they have a good role in our lives. It's just not with this. So I just wanted to say that if you have a patient who does have GI side effects with one GLP-1 or GLP-1-GIP, whatever it is, go ahead and try a different one because the side effect may be different. But also you see nausea that is self-limiting and occurs when you increase the dosing. But if you have someone who has a lot of nausea and vomiting, I tend to go back and talk to them about portion sizes, eating less, getting rid of the fat in their food, you know, all of those things that we teach people because, you know, we know so much about the medications now that I see very little actual nausea, vomiting, more of as we titrate and then it goes away kind of nausea. Well, thank you for that. If I could make just one comment about the compounding too. I don't know if anybody remembers, but a year or two ago, maybe a little longer, there was a lot of concern about contamination in metformin from various generic manufacturers with some carcinogenic molecules that were, you know, a by-product of some of the manufacturing. And we caught that because those medications are actually tested and those are part of the FDA pathway. We have no idea how these compounded drugs are made, what they are contaminated with. If anything, they may be perfectly fine. They may not be so fine. And that scares me. So I recommend my patients don't go down that pathway. I'm going to stick with you, Dr. Pratley, for this one. This particular question was very specific. It was like, you have a patient who is on high dose statin, who seems to be developing diabetes. Would you choose an SGLT-2 or a GLP-1? You're muted. Sorry. That's a really good question. So a couple of things. One is, you know, the statins are associated with increased risk of progression to diabetes. The risk is small. It's around 11 to 14%. They calculate that that works out to be an extra three or four months with diabetes. And the benefit from the cardiovascular risk reduction with the statins more than outweighs any risk associated with diabetes. That's the first point. Patients should stay on statin. Your question was actually, what drug should you choose? That depends upon the other comorbid conditions. Why is the patient on a high dose statin? Do they have pre-existing cardiovascular disease? If they do, then regardless of their A1c, regardless of whether or not they have a diagnosis of diabetes, there are drugs, GLP-1 receptor agonists, that are indicated for reducing cardiovascular risk. Semaglutide in either the diabetes dose, if they have diabetes, or in the obesity dose is indicated for cardiovascular risk reduction. I think that's great. That's, you know, we're getting a lot of the questions regarding cardiovascular, you know, and I think many of you are thinking in an in-depth realm. You know, I see several that ask, you know, should I do SGLT-2? Should I do GLP-1s? And I think, and I like that you're thinking, I don't want you to feel like you're doing a wrong answer. Many of these agents have dual effects. Many of these agents have complementary effects. And I know you guys all want to do the best for your patient, but remember, you look at the person in front of you, you have a shared decision, you talk to them about the benefits of each different therapy, and then you look at the secondary benefits as well. When you go, what other additional things? Do we need weight loss? You know, are we looking at kidney? Are we looking at heart failure? And I know it may sound, you know, like you're literally following them through that. And I'm going to just take a moment, not to, by any means to, but we've gotten three questions regarding type 1 diabetes and GLP-1s and SGLT-2s for weight specifically, and cardiovascular. I'll take that one as I'm due to be presenting in the future with this. So again, we do not have any indication for SGLT-2s or GLP-1s for type 1 diabetes, but I will tell you that they also have kidneys. They also get heart failure. They also get heart disease, and they also struggle with excess adiposity. And so one of the most important things to do is to treat the patient in front of you. So there are times that you may decide to choose agents that help with secondary weight loss. In the realm of GLP-1s, I will tell you that GLP-1s seem to be a little bit easier to incorporate in terms of the science and the insulin reduction. We do not really have an issue with DKA. You have to be mindful of hypoglycemia. Of course, CGM, the standard of care for all persons with type 1 diabetes, and how to navigate that volume loss and the such you're going to have to do. SGLT-2s are a different animal. I never use them in ketosis. People who presented with ketosis, especially if you're using it for heart failure or kidney protection, like our colleague said, we are all getting very anxious in a great way looking for that ketone sensor coming out. So, so exciting. I think we're going to learn a lot. And we're going to be able to know how to safely use medications that aren't indicated for type 1, but may have secondary benefit for those individuals. And so I like how you're thinking. I like how you're going in that direction. And it's great. But just continue to practice in a responsible way. So just about one more type of question that we see, and this has come up a couple different times, is metformin dosing and kidney disease. What do you guys do with metformin, metformin dose? And when do you reduce it? At what level? That's a Curtis question. That's a Curtis question. No, I think when you get to 45, you should definitely be reducing the dose. And the reason why, right, make it clear, not the 45, not the age, 45, the GFR. 45, the EGFR. Yeah, I mean, yeah, at an EGFR of 45, I think is when you need to consider reducing the dose. And that's based on pharmacokinetic data. I mean, the data shows that you can get about the same level with 1000 milligrams a day, as you could with 2000 milligrams a day when you're above that. So usually I limit it to 1000 when we're below 45. And I do stop at around 30-ish, 25. I think it's important to remember that. I don't think it really increases the risk of lactic acidosis, but I do think that there are people who are trying to prove that it does, and I don't want to be a part of that. So I certainly stop at around 30, 25. Do you ever have any patients on GLP-1s who are on dialysis? I have. And they've done fine, as it turns out. Now, these are people that entered and had reduced kidney function and were on a GLP-1 receptor agonist, and they just ended up on dialysis, but they did fine. I think you have to be a little bit careful when initiating a GLP-1 receptor agonist in people who are on dialysis or have end-stage kidney disease, because they are a little bit more prone to issues like nausea. And we also want to pay a lot of attention to the weight loss effects in these people. Now, many people on dialysis can stand to lose a little weight, but you also want to pay attention to whether or not they're losing muscle mass. And there is such a thing as too much of a good thing. So they're a little bit more fragile, a little bit more difficult to manage, but in my experience, they are also benefited by the GLP-1 receptor agonists. You know, Eden, the one thing that hasn't come up tonight, and I'm really excited about it, is nobody's asked us any questions about sulfonylureas. Yes, we don't want to use those. Yes, and I suppose we can end with a very controversial question before we wrap it up. And I will tell you, faculty, we got over 100 questions. We didn't get to all of them. We tried to get to the top of line ones. I like how everybody's thinking, and stay tuned. We still have more presentations in the future that can answer some of your questions. But a lot of discussion of, do you feel comfortable, we won't go into the weeds because this is a deep one, but do you feel comfortable with some of the shortages of the GLP-1s of switching to other GLP-1s? Do you stop it? Do you wait? Do you switch? What have you guys been doing to try and overcome this? I feel comfortable switching. This is a nightmare for my patients. I had started a patient on, I think it was terzapatide. Good news, the insurance covered it. Bad news, there is none within 450 miles. Curtis, what is the article that was in Spectrum that, I think it was last year, that actually gave people a chart on if you have to switch them from one drug to another, how to safely do it and how to do it. Do you recall? I thought you might've been one of the authors. No, I'm not one of the authors, but I do remember that. And it was, we had a section on GLP-1s. I think Dr. Pratley was involved with some of that. So he wrote an article for one of those, but it wasn't that particular one, Dr. Pratley. You didn't- I'm pointing fingers and none of us can remember. He didn't write that particular article, I don't believe. I think Josh may have written it. But anyway, I agree that it depends on how long the shortage is going to be, because remember how long these drugs last too. So if it's going to be a week or two, sometimes I just wait. And sometimes if I can get the lower dose, I might go down to the lower dose. I rarely jump a dose because I'm concerned about that. And then if I have to, I go, but this is a nightmare. It truly is a nightmare. Yep. We just wish you all the best of luck in navigating through that. Continue these medications. These are chronic diseases that we want to manage. We don't want to let it slip through our fingers. We want to keep pressing in and doing that. And with that, I want to thank you from all of our faculty. What a deep dive, what a great presentation for us. We hope that you found this webinar discussion and case study approach insightful. Please visit us at professional.diabetes.org to join or renew your American Diabetes Association membership, access it, and you can get those benefits. We've talked today about the diabetes care, diabetes spectrum, clinical diabetes, all the different subscription. You can also get registration discounts to the scientific sessions and clinical update conference, free members only webinars on diabetes technology and primary care, as well as access to the latest advancement in those related topics of diabetes technology treatment and education. Again, thank you so much for staying tuned. Learn more if you found it very insightful and are eager to deliver some additional things. We invite you to enroll in some of the upcoming courses, Beyond the Basics, Unraveling Challenging Type 2 Cases, Expanding Your Knowledge and Refine Your Skills, and Navigating Intricate Diabetes Scenario. Register now on professionaleducation.diabetes.org. Thank you so much and have a great evening.

Dr. Eden Miller

clinical faculty members

diabetes management

glucose-lowering medications

SGLT2 inhibitors

GLP-1 receptor agonists

individualized treatment plans

medication side effects

collaboration with specialists

evidence-based approaches

comprehensive diabetes care