Welcome, everyone, to today's webinar on the American Diabetes Association Standards of Care in Diabetes 2025. The purpose of today's webinar is to highlight important updates to this year's standards of care and how these changes impact clinical care, especially as they relate to type 2 diabetes, cardiovascular disease, and chronic kidney disease. The standards are a living document and are intended to provide clinicians, patients, researchers, payers, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care. On this slide is the American Heart Association disclaimer, and this slide lists the faculty disclosures. My name is Dr. Alexander Chang, and I will be moderating today's program. To share a little bit about myself, I'm an associate professor in the Department of Nephrology and also the Population Health Sciences at Geisinger Medical Center in Danville, Pennsylvania, where I see patients with kidney disease and hypertension, a lot of diabetes patients, and conduct clinical research and quality improvement population health activities trying to improve cardio-kidney metabolic health. I've had the pleasure of serving on the AHA and ADA for the last couple of years, and it's also my pleasure to welcome our esteemed expert to today's webinar. We're joined by Dr. Dennis Brumer, staff cardiologist and director of the Center for Cardiometabolic Health. He's a professor of medicine at Cleveland Clinic, Lerner School of Medicine, Case Western Reserve Medical School, and Dr. Brumer specializes in preventive cardiology, particularly in the comprehensive management of cardiovascular risk and metabolic control of patients with diabetes. He has a special interest in cardiac intensive care, echocardiography, and is board certified in internal medicine, endocrinology, cardiovascular disease, and echocardiography. Please note that there will not be any CEs offered for today's webinar, but we are excited to provide you with this important education session. We'll be hosting a Q&A session at the end of today's presentation. Please use the Q&A feature to submit questions, and we'll try to answer as many questions as possible. I'll turn it over to you, Dr. Brumer. Dr. Chang, thank you so much for the kind introduction. I think this is a fantastic opportunity for us to really review some of the main aspects of cardiovascular care for people with diabetes. We will go over some of those changes and some of those new guideline recommendations. I've been sharing the cardiovascular section for the Guideline Committee for the past three years, and we've made notable changes on really all aspects of cardiovascular care over the past few years. We have made changes on the blood pressure goals. We have made changes and simplified the lipid management. And of course, we have adapted the guidelines to the evidence from new agents, which we use to prevent cardiovascular disease and to improve glycemic control in people with diabetes. So, we will go over those four pillars of cardiovascular care for people with diabetes. We will go over some of the evidence, but it's mostly a review, and we will also look a little bit at the screening recommendation, and then Dr. Chang will share a few cases and some important new discussions on kidney disease with us. So, I think first it's important to highlight that comprehensive management of all risk factors is really what makes a difference. This was first shown by the STINO2 trial, which was a multifactorial intervention trial that really addressed blood pressure, lipids, smoking, albuminuria, hyperglycemia in a comprehensive fashion, and really showed a 53% risk reduction in cardiovascular outcomes. So, this was one of the first key landmark trials that I would like to mention to support we have to look at all risk factors in combination and combine this with new treatment approaches. When I see patients, I encourage them by a cohort analysis in addition to the prospective randomized STINO2 trial that was published in 2018, the New England Journal of Medicine, which looked at a large group of people, 200,000 people with diabetes matched to 1.3 million control people, and showed really when all the risk factors, no smoking, cholesterol, blood pressure, hemoglobin A1C, when those are combined, controlled, people with diabetes have essentially no excess mortality compared to the general population. I think this is very reassuring that we can manage cardiovascular risk in people with diabetes. Now, there are a lot of barriers, of course, to implement these strategies, and I think we have to keep working on this. So, this initiative is one important aspect of education and really going over some of the evidence. So, I'll briefly talk about the glycemic management. This is the first aspect on the left, and this is the algorithm for glucose-lowering medications in people with type 2 diabetes. And when we talk about people with type 2 diabetes, the vast majority of people will have either indicators of high cardiovascular risk as shown in the second column here, overt atherosclerotic cardiovascular disease, signs and symptoms of heart failure, or CKD. So, for those people with diabetes, the most important aspect of treatment for hyperglycemia are really medications not just to treat elevated blood glucose levels, but to reduce those outcomes of atherosclerotic cardiovascular disease, heart failure, and CKD. So, people that fall in this category should be treated with either a GLP-1 receptor agonist with proven benefit demonstrated in cardiovascular trials, or an SGLT2 inhibitor. If there's heart failure, SGLT2 inhibitor, CKD, SGLT2 inhibitor, ultimately GLP-1 receptor agonist. For people with atherosclerotic cardiovascular disease, actually the ADA recommends, it says, or here, actually there is a class 2A recommendation to consider combined treatment with an SGLT2 inhibitor and a GLP-1 receptor agonist for additive benefit. So, ultimately, this is the goal, combined treatment in these people. So, this is for the glycemic management of these people. Now, if we look at the second part, we can look at blood pressure, and we have changed the goals of the past few years based on new evidence. So, recommendation 10.4, the on-treatment blood pressure goal is less than 130 over 80 if this can be safely attained. This has been reduced from previously 140 over 90 to now 130 over 80. Since the guidelines were published last year, there's even additional evidence, the blood pressure road analysis that had shown and supported lower goals for people with type 2 diabetes and hypertension. Of course, as always, we need to individualize the care for our patients and make sure that the blood pressure goal, tighter than previously recommended, is safely attained. When we look at lipid management, we'll try to keep this as simple as possible. Lipid management for people with type 2 diabetes, I think, is actually pretty straightforward, and I will go over this briefly. So, this is for primary prevention. So, those are those people who do not yet have atherosclerotic cardiovascular disease, and those are not the people who you find incidentally on a chest CT scan, done in the ED for shortness of breath, who have, for example, coronary artery calcification. Those fall into secondary prevention. So, this is no evidence of atherosclerotic cardiovascular disease, and people age 40 to 75 use high-intensity statin, and those with—and this is the majority of people with diabetes because the majority of people will have an additional risk factor for cardiovascular disease—the LDL goal is less than 70. So, when you think about primary prevention, those people without atherosclerotic cardiovascular disease, you need to remember one number, that's an LDL of 70, and this includes statins, and if statins are not sufficient to achieve this goal, it may be reasonable to add additional non-statin therapy to these people. Now, if you look at people who already have atherosclerotic cardiovascular disease, stenting, PCI, atherosclerotic cardiovascular calcification, cabbage operation previously, etc., high-risk people with events, the LDL cholesterol goal is less than 55. That is the second limit number you need to remember, and this is usually accomplished with high-intensity statin therapy, and if that is not enough to achieve an LDL cholesterol goal of less than 55, the recommendations are to add azetamide or PCSK9 inhibitor therapy. Keep in mind that in all the trials that combined statin therapy with non-statin therapy, so this is statin plus azetamide plus statin plus PCSK9 inhibitor, the reduction in cardiovascular event rates were mostly seen in those people at higher risk, which includes people with diabetes. So, those are the people who benefit the most from combination therapy, so have a low threshold to add non-statin therapy to statin therapy. Now, treatment of other lipoprotein fractions, this is always a question that frequently is asked by patients, and I would like to point out if the triglyceride levels are elevated, first we look for secondary causes of hypertriglyceridemia, and then we can consider additional medical therapy, particularly if the triglycerides are above 500. That is to reduce the risk primarily of pancreatitis. If there's moderate hypertriglyceridemia and increased triglycerides in general, it is very important to emphasize lifestyle modification. Now, in people with established atherosclerotic cardiovascular disease who are treated with a statin and who have an LDL between 150 to less than 500, the addition of eicosapentaethyl can be considered to reduce cardiovascular risk with the class B recommendation. Now, the last slide is, again, agents with cardiovascular and kidney benefit. I had briefly already mentioned this under the first glycemic management. It is important to address concurrently cardiovascular risk reduction therapy with guideline-directed medical therapy that includes blood pressure, lipids, glucose, antiplatelets, but the vast majority of people with diabetes are actually at increased risk for atherosclerotic cardiovascular disease, have overt atherosclerotic cardiovascular disease, or have signs of heart failure or CKD, and those should be primarily treated with an SGLT2 inhibitor or GLP-1 receptor agonist with proven benefit, and there is evidence to use combination therapy for additional risk, additive risk reduction, and that is actually a class A recommendation in the cardiovascular section of the standards of care. Now, one last couple words on screening, and we'll go over the screening briefly for atherosclerotic cardiovascular disease, for heart failure, and for peripheral artery disease because there are some new treatment recommendations, which I summarize in the next slide. Actually, you can see this is a nice overview that was added this year to the standards of care for coronary artery disease. Routine screening is not recommended if the patient has no symptoms. If there are signs and symptoms, atypical symptoms, or other findings on EKG, routine echocardiogram, or again, or symptoms, then of course we recommend routine screening methods for the evaluation of coronary artery disease. Now, there is a recommendation to screen all adults with diabetes for heart failure, and this is with measurement of BNP or NT-PRO-BNP. That is because diabetes increases the risk for asymptomatic heart failure. Diabetes itself is considered a risk factor that would be called stage A heart failure, but if they're stage B heart failure, but there are ways now to protect the progression from asymptomatic to symptomatic heart failure, that is from stage B to stage C heart failure, and this is why the screening becomes important, particularly if, for example, you have a patient coming in with diabetes who presents with edema or shortness of air. That would be considered symptoms, and then screening becomes even more important for these people with type 2 diabetes now, or with diabetes in general. Now, peripheral artery disease, when there is a long-standing history of diabetes, advanced age above 65, any findings of microvascular disease, any clinical findings, then we typically recommend considering screening for peripheral artery disease using anchor brachial index testing. I think those are some of the nuances and some of the new recommendations for screening of people with diabetes for cardiovascular risk. Now, I'll turn it over back to Dr. Cheng, and we'll go over a couple cases now to kind of highlight some of this what we discussed. Wonderful. Thank you, and thank you, participants, for putting in questions in the chat. We'll try to get through them either, you know, during some of the discussion or in the Q&A section. So, there's no actual poll here, so don't feel like you need to click on anything or answer. You can answer in your head. That would be great. So, this is a 58-year-old, a Caucasian male with type 2 diabetes, difficult to control hypertension, and severe obesity. The blood pressure is 145 over 80 at the visits. The A1c is 6.4%. Their EGFR is 100, and their urine albumin-crantinine ratio is a little bit elevated at 50 milligrams per gram. Currently, they're on flipazide and metoprolol. So, the question is, what would you do next? A, advise the patient to do home blood pressure monitoring, and as you can see that, you know, this question is kind of around blood pressure, but also the cardio-renal risk as well. B, switch flipazide to SGLT2 inhibitor or GLP1 receptor agonist. C, switch from metoprolol to an ACE inhibitor or an ARB. D, all of the above. So, I think the answer here is really, you know, we want to make sure that the blood pressure is indeed controlled. You want to make sure that they're on the appropriate guideline-recommended therapy for their concurrent conditions, including kidney disease or coronary artery disease with the ACE or ARB, and of course, we want to encourage more use of cardio-renal risk-reducing medications. So, this is a nice flow diagram from the guidelines, and a couple things I wanted to point out is that, you know, it talks about the initial blood pressure, and the reason why it does that is because there's pretty good evidence, really, that, you know, if the blood pressure is pretty high, say, above 150 over 90, you know, you really should be starting with two agents, and of course, a lot of times, you're seeing them or sharing them with other clinicians, so they may already be on one agent, but, you know, we really should be more proactive in managing hypertension and knowing that, you know, you actually have multiple different ways to get the blood pressure down. The days of sort of maximizing one medication and then waiting and then increasing the other one are changing. You know, there's a lot of trials that are looking at combination pills versus monotherapy. You know, one of the common things that I, you know, hear is that, oh, well, I'm afraid that they're going to be on, you're going to have multiple adverse effects if you're on more classes. But actually the trials do show that you don't have more adverse events, you know, starting combination therapies. So usually tell the patient that, you know, we're going to hit the blood pressure for multiple different angles. And really it's just about, you know, getting to the goal of getting your blood pressure under control. And, and rather than focusing on, oh my gosh, there's more medications. And of course there's combination pills now too. So those pills often will have better adherence and are associated with better outcomes in the long run. Of course, we're going to address the lifestyle management. I think, you know, with all of the different things that we have in store with the GLP-1, you know, thinking about obesity and the role that that could play in the regimen as well as important on top of all the dietary stuff and making sure you refer them to a dietician or a weight management clinic as appropriate. And then if they have albuminary or coronary artery disease, you really want to make sure they're on an ACE or an ARV. This has not really changed, you know, but even, even still, you know, we still see patients that are maybe on suboptimal dosing, or for some reason, maybe their creatinine bumped a little bit and then it got stopped. But, you know, really have to appreciate that, you know, you could have this transient worsening of the kidney function when you start these medications, but in the long run, they're going to be better served. And if you're not sure, you know, of course involve a kidney doctor and a nephrologist. And then, and then in terms of, let's say they have albuminary and the blood pressure is quite elevated, then this puts in the guideline here that, you know, you start the ACE or ARV along with the calcium channel blocker or a diuretic. And I think there's, you know, you probably look at the patient's various, you know, considerations of what they might be afraid of in terms of adverse effects with when you're choosing exactly what and looking at their potassium levels to their, you know, more their potassium from the higher side, I would like to use a diuretic, for example. And then after, you know, you've treated their blood pressure at that visit, the important thing is appropriate follow up. One of the things from recent trials that have included a lot of diabetes patients, including a trial that was done in China that was kind of like the sprint trial, but for patients with diabetes, they often are involving home blood pressure monitoring. And so if I'm really, you know, trying to do a good job with my patients, and their blood pressure is out of control, I always encourage them to do home blood pressure monitoring. But you know, making sure they know how to buy an appropriate blood pressure device, making sure it fits, make sure that they are educated on how to do this. You can even do some billing for self measured blood pressure, if you get that set up correctly. And then you can use that to titrate their medications further and add more agents as needed or maximize the therapy until you get under control. And then lastly, of course, you want to consider a mineralocorticoid receptor antagonist, if you have a patient with resistant hypertension, or they're not tolerating one of those other classes. And those are really kind of a game changer here. And of course, there's also the consideration that they have persistent albuminuria. Saneranone has been shown to further reduce cardiorenal risk in these patients. All right, this is the second case, a 76 year old African American male with type two diabetes, hypertension, hyperlipidemia, coronary artery disease, ischemic cardiomyopathy, ejection fraction 35%. Stage four kidney disease here for follow up. Overall, they say they feel great. They're not experiencing any heart failure, complaint related complaints and their exercise tolerance is good and everything looks good on exam. Their blood pressure is well controlled. They're A1C 6.8%. You know, you look at the EGFR trend, and two years ago was 28. Last year, it was 26. And this year, it's 24. You know, the patient's concerned about the kidney function, the potassium is 5.2. And their albumin cranial ratio is 175 milligrams per gram. So the medications they're currently on are lisinopril 40 milligrams, carvedilol 6.25 twice a day, torosemide 20 milligrams per day and rosuvastatin 10 milligrams per day. So the question here, you know, the potassium is a little bit high, it's 5.2, the GFR is dropping about two per year. At this point, are you going to stop the lisinopril, decrease the lisinopril? Again, we don't have a poll set up. So please just, you know, think about this through your, and we will discuss. Start potassium binder or start SGLT2 inhibitor. So, you know, I could see that all of these seem like they could be reasonable options. But really, you know, what we want to do here, and I'll just go back to the case here is, you know, think about, okay, you know, we know that the patient has so many risk factors for kidney disease and progressive kidney disease. You know, the GFR is dropping, but that doesn't mean, you know, we often jump to the conclusion that it must be one of the medications they're on, we got to stop these medications. But really, the studies show that, you know, you try to optimize the therapies based off of what the research tells us. And for this type of patient, we do have solid evidence that adding an SGLT2 inhibitor should reduce the risk of heart failure events and potentially kidney failure. A little bit trickier since they also have, you know, both conditions. But the other side effect about SGLT2 inhibitors that has been studied is that it tends to decrease the potassium a little bit as well. So that's kind of a nice side effect that you may see. So and then of course, it's indicated for kidney disease itself. So there's multiple indications. And I think that should really give you the best benefit there to try to tackle those things. I don't have a follow up slide for, you know, what happens afterwards. But also realize that you start the SGLT2 inhibitor, and the GFR can drop a little bit. Again, you know, if it drops, you know, down to 20 or 19, that, to me seems pretty reasonable, actually, and kind of what you would expect with the acute effects of the SGLT2 inhibitor. But, you know, really just try to make sure that patient's feeling fine, make sure that their volume status is, you know, maybe you have to adjust the torsomide. Sometimes, you know, you get the monological directed therapies, and they end up not needing as much or even needing the loop diuretic. And I'll let Dennis comment too, after I show this slide. So this is a, this is talking about recommendations to reduce the risk of symptomatic heart failure in the guideline. Dennis, you want to take this one away? Yeah, I think, you know, the, if people with symptomatic heart failure, I think you want to first, of course, identify the cause of heart failure. Typically, if patients have symptoms, and you obtain an elevated antiprobian P, the next step would be if that's elevated, of course, to look for structural heart disease, which could be either due to reduced ejection fraction, heart failure with reduced ejection fraction, or increased filling pressures, which are due to heart failure with preserved ejection fraction. And particularly in the latter, a lot of the people would have hypertension, which should be treated first time with ACE ARB or beta blockers. If patients have, for example, wall motion abnormality or reduced ejection fraction, history of coronary disease or myocardial infarction, these people, of course, should also be treated with ACE inhibitor beta blocker. If people are at high risk for established cardiovascular disease, next treatment then, of course, would be an SGLT2 inhibitor. This is to reduce adverse outcomes in people with heart failure. And if there's pre-existing CKD, it would be an SGLT2 inhibitor, probably still first-line therapy. If there's particularly albuminuria, finerenone may has been shown in cardiovascular outcome, tries to reduce associated cardiovascular risk. So, that's kind of an add-on. So, this is sort of the algorithm that we use in people who have diabetes and diagnosis of heart failure. Wonderful. Thank you. And this is another slide just kind of showing from US health system data that even pretty recent data, I think this is up to 2022, we have low utilization of SGLT2 inhibitors, even among those who have a class one recommendation for its use in type 2 diabetes. And, you know, again, there is an association with reducing risk of hyperkalemia that I wanted to point out. And that also that the EGFR cut points have evolved over time. There's more and more trials. In general, the EGFR beta is equal to 20. You can start SGLT2 inhibitors to reduce cardiovascular risk. And then, you know, even if it drops below that after you start it, you know, you have to assess their volume status and, you know, how they're feeling, everything, their blood pressure and all that. And in the trials, they actually will keep them on the drug as long as possible. So, that is kind of how we kind of simulate using it to reduce cardiorenal outcomes. All right. So, for CKD, these are pretty much the same as before, but just to reiterate, you know, what you need to do, make sure that you assess kidney function. And we're really thinking about kidney function as a kind of a more of a multi-dimensional thing rather than just, you know, EGFR. We're also looking at evidence of kidney damage. So, you really want to do the serial albumin-cranium ratio as a measure of the kidney health. And for people that have established kidney disease, you know, depending on their stage of kidney disease, you might monitor it one to four times per year. You know, one of the good things about doing it, because you might say, well, it's the same, you know, what's the point? But one of the good things is if you start a new medication that should have a benefit on cardio-renal risk, usually you will see a reduction in the albumin areas. So, sometimes that's something that's very encouraging for patients that, you know, okay, we actually see something tangible that, you know, I used to have 1,000 milligram per gram of albumin area, and then we started all these medications, and we've gotten it down to, you know, sometimes even normalizing it from that point with everything we have. And this is just the heat map that we use for kidney disease, just showing different levels of kidney function on the left side with the stages, and then the albumin area categories on the top there for mildly increased albumin area and severely increased albumin area, and some suggestions about the frequency of doing labs and, you know, which patients might be better to treat and refer to a nephrologist at different levels as we try to manage these patients together. In terms of kidney disease management, you know, you really, a lot of it looks very similar to overall diabetes management. Of course, the dietary stuff is a huge part of kidney disease, and the first-line drug therapies that we have involved, you know, the SCLT2 inhibitors that we mentioned, you can use metformin up to EGFR 30, make sure that you adjust the dosing as the EGFR gets lower, and then stop it at below there. Maximizing the RAS inhibitors, if there's albumin area or hypertension, the statin usage is considered a high CBD risk factor, so everything should be fairly similar to what was described already, and then on top of the SCLT2 inhibitors and metformin, you know, combining with GLP-1s, if needed to achieve individualized glycemic goals or if there's, you know, other risk factors that you want to address like obesity or uncontrolled A1c, and then considering adding on non-steroidal MRAs if there's residual albumin area and the potassium level is normal, and of course, you may end up needing to consider potassium binding agents if, you know, you get to pretty more advanced kidney disease and you're unable to control the potassium through lifestyle management and trying to keep them on the same guideline-recommended therapies. All right, well, I think we're going to open it up to question and answers, and I know there's plenty already in the chat here. Well, maybe I can ask Dr. Cheng while people are pulling up their questions. If you look at the first…the first patient case is kind of a typical scenario, right? So, although oftentimes the patient will be on metformin and metoprolol as first-line therapy, and in fact, even now, several payers still mandate that patient is on metformin first-line therapy from glycemic control, although all the recommendations that we discussed still make SGLT2 inhibitors and GLP-1 receptor agonists for those patients that we reviewed first-line therapy irrespective of whether a patient is treated with metformin or not. I think I wanted to point that out. The other part is, of course, coming from the cardiology side, I was missing the statin, and, you know, those are classical scenarios where, again, I highlighted that we have to look at everything together. So, yes, of course, we want this patient to be treated with an SGLT2 inhibitor with an ACE or an ARB, but keep in mind this was a patient with type 2 diabetes who obviously should be treated with high-intensity statin therapy. As we discussed, I think, finally, when would you consider adding a GLP-1 receptor agonist for this patient? This is a patient with increased cardiovascular risk and severe obesity, so while, of course, we look at the kidney function and an SGLT2 inhibitor, but here you could even argue, irrespective of the hemoglobin A1c, you could consider for weight management strategies to treat this patient also with a GLP-1 receptor agonist, so then you have the whole spectrum of cardiovascular risk reduction care. The second case I noted was a patient with rosuvastatin 10. Now, that's probably something we would want to bump up to high-intensity statin therapy as well, so something to consider. Just maybe one or two words from the cardiology side about the cases to add. Thank you, Danis. Yeah, I totally agree with you. I think the role of GLP-1s in kidney disease is interesting because it's just one of the drugs that received an FDA approval. I don't know if I'm allowed to say brand names, but it's a maglutide, and so certainly in these types of cases, it may not be an exact perfect answer of which one to start first. You know, if you're dealing with different levels of A1c, different risk factor profiles of body mass index of 40 versus 25, I think you have to take all these things into consideration and sort of the patient preferences. Of course, maybe both in many instances if we're able to get the patient those medications. Well, I had looked at some of the Q&As, and I put down some notes. Well, I think at least a couple of people were wondering about the use of omega-3 fatty acids, whether prescription or over-the-counter and what the role is for hypertriglyceridemia currently. So, I think, you know, for hypertriglyceridemia, I do not recommend fish oil because of lack of cardiovascular risk reduction. The only prescription-grade fish oil that has been shown to reduce cardiovascular risk is icosapent ethiol. That's in the guidelines, so that's kind of—that's what we recommend. Supplements, keep in mind, prescription-grade fish oil does not equal supplements, okay? So, there are no fish oil supplements with proven cardiovascular benefits. So, we do not recommend fish oil supplements in general. Thank you, Dr. Bremmer. And that's something that, you know, there is some other evidence in kidney disease, and I think I've sort of shifted my practice away from using them as well. Now, another series of questions I saw in the question and answer was around ENT testing, which is very interesting to me. So, you know, the thought about screening for heart failure in patients that are asymptomatic, who have diabetes, is there a recommended frequency of screening? Any thoughts at that? I think there is no perspective evidence evidence that subsequent annual screening is recommended. So the guidelines are not recommended, recommending currently subsequent testing. I think testing is recommended when you see the patient initially. When a patient has symptoms, of course, you would want to test again. Another question I see that's pretty common is any thoughts on CoQ10 supplementation with statin use? The data, so it's not part of the recommendation and it's not part of the recommendation because lack of consistent benefits seen in clinical studies. Now, if patients come to us and are on it and have the feeling that it reduces their risk for myalgia, I may not take patients off the CoQ10 but I usually do not start it. Yeah, the question I see that looks like probably I should answer is on calcium channel blockers. Can calcium channel blockers increase albuminuria and should you favor ARB or ACE or hydrochlorothiazide in those patients who need greater than one agent? So that is a great question. There is some experimental evidence that dihydropyridine calcium channel blockers can increase albuminuria and sort of disrupt renal autoregulation. In general, if you use it along with the ACE or an ARB, it doesn't seem to have any increased risk and really the risk of the albuminuria is usually if they're on a dihydropyridine calcium channel blocker and their blood pressure is totally out of control. So they're sort of out of that auto regulatory zone. So I absolutely would try to combine it with an ACE or an ARB. I think one important question that I see here, again, we're trying to go through as many questions as we can. So for the audience, if you're disappointed that your question does not get answered, feel free to contact either of us later on. But I think one question here that I think is very important that we still frequently with is in totally asymptomatic active person age 40 to 75, if this person has an elevated calcium score, are they considered to have coronary artery disease and then proceed to an echo, et cetera? So I think first this highlights a common dilemma. The question is why do we do a coronary artery calcium score in a patient or in a person with diabetes? That's not really recommended, right? So if you look at the recommendations, calcium score may facilitate risk stratification and statin treatment recommendation in intermediate risk people based on the pooled cohort equation and the risk calculator. Now that does not apply to a person with diabetes. So a person with diabetes should be treated with high intensity. So a calcium core score is not really recommended. But if that was done anyway, then I would consider this patient to have coronary artery disease. I think a calcium score does raise the risk of course, and should be considered coronary artery calcium score. Now there's evidence that people even with diabetes with a zero calcium score have atherosclerotic disease, non-obstructive on coronary artery CT angiograms. So meaning a negative calcium score does not confer a risk of zero in a person with diabetes. That's why we don't do coronary calcium scoring in people with diabetes and it's not recommended. I saw a couple of questions about SGLT inhibitor usage in type 1 diabetes. Dr. Brummer, any thoughts on where we are with research on that? I mean, it's not currently recommended. The research is evolving and I think the guidelines will adapt. Thank you very much. There's a question about using albumin to cranial ratio versus protein to cranial ratio in screening. So yeah, this is another great question. The albumin to cranial ratio is advantageous in that it's more sensitive at the low level. So generally for diabetes, we would recommend using an albumin to cranial ratio. You may see a lot of nephrologists ordering both an albumin to cranial ratio and a protein to cranial ratio. Sometimes we do that to try to evaluate for other types of proteinuria that are sort of non-albuminuria protein. But yeah, in general for most of your diabetes patients, just using an albumin to cranial ratio would be sufficient. Thank you. And there's a couple of questions about metformin and I agree, it's always kind of interesting writing these case presentations and then thinking about all the other possible answers. But I should agree with you, Dr. Berman, the first case, statin could be added. You could add metformin as well. You will have some associated weight loss with metformin. I don't have the number of the magnitude of it, but I know from the comparative effectiveness literature out there that the amount of associated weight loss with metformin is definitely a lot less compared to GLP-1, at least the newer GLP-1 in general. That doesn't mean that it shouldn't be considered and used as indicated for sure. I think one patient that, one comment here that is, we encounter quite frequently with kind of, which kind of has to do with remission of diabetes. So say there's a patient with a history of type 2 diabetes, no heart failure, no CKD, the hemoglobin A1C that's presented here is 5.3, bone blood glucose monitoring, all good. Patient is taking Jardian, Mpagliflozin and metformin. If you see this patient as a new, would you recommend continued treatment with Mpagliflozin and metformin? I think this is, you know, this is a good question. I think when we have a treatment that works, you know, would we discontinue the treatment? We don't really discontinue a statin for a patient at risk, right? We continue the statin treatment. And I think if something works for a patient and the patient is tolerating this regimen very well, I would not necessarily see a reason to discontinue any of those in this combination treatment. I don't know what you would practice Dr. Cheng, but we typically don't discontinue medications that work or that have sort of induced remission. Yeah, I think, you know, just tying it together with some of the other comments in the Q&A, I mean, a lot of it also has to do with some of the, you know, where the patient's at, right? If they're having issues affording medications and, you know, certainly if it seems like it's working and we know that it works and reduces cardio-renal risk, you know, I would try to keep them on, but if they're, you know, having problems paying their bills, you know, of course, you know, we would consider that and then with close follow-up. Another question on there, I think there was a couple about combination treatments, whether it's better than monotherapy. And, you know, of course it could be better in any number of outcomes. I will say that if you're talking about kidney disease outcomes, in the recent semaglutide study in patients with diabetes and kidney disease, they did not require them to be on a SGLT2 inhibitor since it was probably going on concurrently with the other trials. But, you know, when you pull all the data together, it looks like the effects of GLP-1s on reducing risk of the cardio-renal outcomes, it seems to be consistent whether they're on an SGLT2 inhibitor or not. So it would suggest that, you know, adding more should further reduce their risk. And then, of course, that goes along with this polypharmacy question. I'd be curious what you think, Dr. Brimmer, how do you balance the risk of polypharmacy in older adults with increasing number of medications that are indicated that, you know, we get more and more, you know, better and better in cardio-renal risk reduction, you're gonna require more and more medication class. Yeah, I think, I mean, I think you have to individualize care and you have to make sure that the care you provide is safe and that the patient is able to follow and pay for these medications. I think, again, there are recommendations, guidelines, but then we're still acting as providers who manage these patients. So there's always some individualized aspect of care. I mean, we know that in older patient, there's generally, for example, statin undertreatment and treating effectively does reduce risk. Now, do you need to do that? And every patient depends on what you, you know, what the patient's individual situation is. I think these are all great questions to the audience. I think this is fantastic. I think there's one question here that, you know, statin therapies widely underutilized, which type of healthcare provider should take the lead in ensuring that patients with type two diabetes are prescribed statin? I think any healthcare provider. I mean, you all know the recommendations. If you see the patient, just go ahead and treat this patient effectively. I think it can be any physician. Often, it's the primary care physician or, you know, doesn't have to be the cardiologist. This is usually pretty straightforward. I think another great question that I see here, what is the current position of sulfonamides in the management of type two diabetes? Long the second step of therapy after metformin, still frequently used, but I think clearly we have much better choices, which are much safer. There are meta-analysis, which actually show increased cardiovascular risk of sulfonamides in second line, previously second line treatment. So I think if we have better alternatives, I would much favor those. And that's what the guidelines recommend. Yeah, and I see a great comment, which I forgot to address there, was about the resuvastatin dosing. And I think this is an interesting one because, you know, we're sort of prescribing higher doses. According to the manufacturer, the max dose is 10 milligrams. And I was trying to look up the EGFR cutoff and I'm struggling right now, but there's a certain EGFR cutoff. I can't remember if it's exactly where it is, but definitely more advanced kidney disease. There is some renal clearance and some potential associations with kidney damage at high doses. So yeah, this is a tricky one where I've seen a few cases where, you know, the patient certainly needs to, we need to control their lipids as well as possible. And then some of them will actually have at the high dose some protein area that does seem to be associated with it. And then you reduce the dose and then the protein area goes away. So it's something I think is important to consider. You know, generally, I would follow, you know, the manufacturer guideline on the dosing. The common question that we get is there such a thing as too low of an LDL? This is a very common question. If we, so the answer to that is no, not as far as we know. There are people who have been treated particularly with statin plus PCSK9 inhibitor in the primary outcome trials, Odyssey and Fourier, which actually entered the trials with already a pretty low LDL. Let's say you have a patient with an LDL of 65 and the patient has established atherosclerotic cardiovascular disease and type 2 diabetes, you would push the LDL to less than 55. And you may want to use a PCSK9 inhibitor which may bring the patient way down to 10 or 15. And those patients were actually analyzed in a subgroup analysis out of those trials comparing an LDL of 10 versus 30. That was actually an almost 30% risk reduction for cardiovascular event when the LDL goes from 30 to 10. So I'm not saying this is part of the guidelines but there were no notable adverse outcomes. Also in the one question that always comes, does the brain need LDL cholesterol? There is no signs of cognitive impairment with targeting lower LDL. In fact, there's some evidence that vascular dementia is actually reduced by LDL cholesterol reduction. So I think this is a good question that we frequently get. Dr. Brummer, I was wondering, sometimes I see patients as well as these folks that encounter patients that really should be on a statin and I'm not really sure why they aren't and you kind of inquire a little bit and you say, I can't take that. So how do you go through that? What's your playbook for that situation? So I think obviously first you have to, we're talking about people with diabetes. So we have an indication so we can mark that check. If people cannot take a statin and have previously failed two high intensity statins, which would be a resverstatin or a torvastatin, we can attempt to get approved non-statin drugs. Next step would be either, you know, either bempedoic acid, which has cardiovascular benefit out of the clear outcome trials or PCSK9 inhibitor therapy often depends a little bit on insurance. If that is denied, then I think we can go back and try alternative statin dosing or, you know, lower intensity statin dosing. I would say in general, it's rather uncommon that there's not a regimen that we find that works for every patient. You just have to keep working with patients. Another question I saw up there in the chat was around side effects and management with SGLT2 inhibitors. So one of them was about, you know, that patient with heart failure already on a loop diuretic who's asymptomatic. You know, should we be proactively decreasing the loop diuretic dose when you start the SGLT2? And then also, you know, if somebody has incontinence, is that, how much of a contraindication is that for SGLT2 inhibitors? So happy to hear your thoughts, Bennett. Yeah, I think, you know, typically in clinical practice, when we have a patient with heart failure and we add an SGLT2 inhibitor, we often don't proactively reduce the loop diuretic, but we do obviously check a basic metabolic panel after a week. And sometimes, you know, due to the osmotic diuresis, we may be able to reduce the loop diuretic, but it's not the first step. Particularly often when we start the SGLT2 inhibitors in hospitalized patients with diabetes and or without acute decompensated heart failure, often these people have undergone aggressive diuresis and we add the SGLT2 inhibitor for heart failure reduction at that time. So I think it's pretty rare that we would reduce the loop diuretic. Yeah, that's kind of what I've noticed too. Sometimes when I thought to proactively do it, and then I had to, you know, increase it back up because they needed it. So I think just the close monitoring is the most important there. And then I saw a comment about non-dihydropyridine. So right to like Daltai's, there are some studies showing that that does reduce albuminuria actually. So not to, you know, in contrast to the dihydropyridine and calcium channel blockers. The thing with, you know, some of these studies is, you know, we don't really have like big CVD or renal outcome, you know, trials with these things. So I sort of use that type of information to help guide practice. But, you know, I don't, I know some people will use non-dihydropyridine, but I find that it makes it a little trickier when, you know, with interactions with Daltai's. And so it's not something that I personally want to do. And then another question about extreme blood pressures. I mean, really spironolactone is what you need to try there in making sure adherence to medication because most patients unfortunately are not perfectly adherent to the blood pressure medications when there aren't that many. And I believe we are at time here. So thank you all for these great questions. And I'm sure we could stay on for another hour to keep answering more of these wonderful questions, but we hope you enjoyed this session. And thank you all for your attention. Dr. Brummer, any final words? I can only congratulate you and I appreciate the amazing questions and alert and smart. So we all appreciate it and are very thankful. Thank you.

American Diabetes Association

2025 Standards of Care

type 2 diabetes

cardiovascular disease

chronic kidney disease

GLP-1 receptor agonists

SGLT2 inhibitors

lipid management

STINO2 trial