Dr. Reza Elahimehr provides recommendations and practice points on comprehensive care, glycemic monitoring and targets, lifestyle interventions, antihyperglycemic therapies, and approaches to management of patients.
Okay we're gonna turn to how do we use S. G. L. T. Two inhibitors and GLP one agonists in terms of our renal outcomes and what's been shown. Um So rosa please uh move us on to that one now to let's see what the recommendations are. Thank you again. Uh So again my disclosures I have no financial ties. Uh Some of some of the slides I figured now that some of my slides are going to be a repetition of what it has been well said before, diabetes is the most common cause of chronic kidney disease worldwide. We know and and this is this is a map from I. D. F. Database at last. As you see the estimated number of adults with diabetes, it's uh is very high especially in the United States India and china brazil also has high approximately one in three adults with diabetes may have chronic kidney disease. Yeah the data from U. S. R. D. S. Annual record indicates that diabetes is the most common cause of S. H. Kidney disease. That follows uh that is followed by hypertension and glamour, glamour nephritis. Clinical manifestations of kidney disease was what we just discussed in the in the previous uh uh talk or presentation from Dr Mindy. But if you mentioned at the bottom of this uh this table uh Reduced year far too less than 60 and two. Less than 30 has significantly increased over time. So back in 1988-1994 maybe it was not as much as what we are facing with or what we are diagnosing or you're seeing these days. It could be, you know, that we are doing better job screening those patients. But nevertheless, here is the reality. We see more of those. This data is from Ann Haynes study KB Go uh kidney disease uh Improving global outcome, that's what it stands for. Um is this providing us with guidelines? And in 2020, for the first time they published guidelines for managing diabetes. And CKD. Very expensive and and very, very practical. It comes in five chapters. Chapter one talks about comprehensive care patient with diabetes and CKD interestingly in that approach. In that first chapter, Wrasse Inhibition comes as part of the comprehensive approach. This cartoon lost rates. Now, how, you know, all patients should have lifestyle modification. Uh Some will benefit from S G L. T two inhibitors and rest blockades. And less number of patients would benefit from anti platelet therapy. Uh we know that real angiotensin inhibitors uh slow down progression of CKD and this is from DR Brenner published in 2000 and one. Loss Orton we have seen many seminar slides in our career about the use of a inhibitors or Arbs and CKD outcomes. Yeah. The second chapter KD Go talks about glycemic monitoring and targeting patients with uh diabetic diabetic CKd diabetic kidney disease classic monitor and setting a target for each patient to uh to to reach for a better glycemic control. It has been the key and diabetes management diabetic kidney disease management. This is another uh you know uh study comparing intense or intensive diabetic therapy comparing to conventional diabetic therapy. Now, we know that sometimes there has been publications about, you know, the benefits or or the risk of intensive diabetic management. But here is about the kidney. We know that if we can if we can uh control diabetes control, have a better estimate control, we can we can improve at these kidney outcomes. It comes in many caveats In Chapter three KD go talks about lifestyle interventions, nutrition intake, physical activity. Um Here's what we have been doing since 1988 between 1988 and 2014. We have been doing glucose lowering medication. We have been targeting grass system. You have been treating status to improve CKD outcomes. But I I don't see much change until now. Up to 2014, or at least up to early 2010 era uh until the new agents came in. And this is another graph showing the trend of diabetic treatment uh And controlling risk factors in in uh in the United States between 1999 to 2018. You see the trend seems pretty much flat except for statins that you might be doing a better job on the status recently. But We have been doing the same thing since 1999, different medications. The top graph shows what diabetic medications we have used so far. And if you if you look at the bottom of that graph, you see a purple and a pink line. That's when Sgst two inhibitors and GLP one agonist destroyed to show up. And that's the only thing that has changed recently. Yeah, clinical trials Uh many since 2013, the orange ones are GLP one agonists and SCL T two inhibitors are pink. You see, most of them are about these two class of medications. And we we have seen great data. We have we have seen great outcomes using these medications and that brings us to Chapter four, how to use anti hypoglycemic therapies for for diabetic kidney disease. Um that was discussed in Katie go uh guidelines in the fourth chapter. Now, let's talk about the GlC two inhibitors in Type two diabetes, the maladaptive up regulation of sodium glucose. Uh co transporter type two. We we should make it short SCL T two inhibitors contribute to uh the main maintenance of hyperglycemia inhibiting these transporters has been shown to effectively improve glycemic control. It can reduce plasma glucose. We can help reducing body weight, blood pressure, even uric acid uh decrease and global hyper filtration, um which is which is one of the pathology. The major uh pathologies that is leading to uh diabetes, kidney disease. Yeah, Presence was published in 2019 chemically follows ng and real outcomes in Type two diabetes and uh the property uh 4400 patients were followed for about 42 months And at the end, uh you see in different uh parts of this these graphs that uh the rate of the srd death from cardiovascular events and composite outcomes of death, cardiovascular and and uh kidney related disease significantly and meaningfully decreased. What is striking to an anthology I'm talking about myself is how they did on treating albumin urea and how they changed estimated gear for they successfully reduced and maintain uh albumin urea. Uh as you see on the top graph, As far as year four and I'll show you more data in other agents like this. Initially we see a drop in G. Fr and here's here's where causes confusion for most other providers. But If you continue the graph, you see after about 18 months, you start seeing the long-term benefit of it. You see G. A forest stays higher compared to placebo. What I was talking about was we see that small initial drop in G. F. R. And many of us decide to change our practice. We say, oh, they didn't tolerate it, creating went up or G fr decline. We are making this worse. We should we should give it some time. We should continue because the benefits are long term can legally foreseen. Here's the table related to those graphs. The major side effect I think is is uh hyper bulimia and and getting dehydrated. A lot of data. A lot of concerns about the risk of amputation, risk of urinary tract infection fractures. Uh They were not consistent. There were concerns at some point. They're not consistent. Maybe a little increase in breast cancer. Not meaningful. I don't know. I'm not sure about that. But the thing that we need to pay attention to or discuss to the patient, give them heads up is making sure that they drink water. Sometimes it can be a challenge. Right? So many of our patients with CKD, they may have a dino they may have heart failure. It would be difficult to say drink more water, but at least we can monitor it. We can monitor it closely. Yeah. Here is uh Emperor uh Emperor reduced an emperor preserved trial. They targeted heart failure patients. Either we preserved ejection fraction or with reduced ejection fraction, but part of the outcome. They looked at the kidney outcomes. They looked at the real functional outcome. What is important here is the same pattern that we saw with Canada lee follows the same thing we see in the G fr Initial and initial drop in G. F. R. At the beginning. But when you continue, you would see the benefit from it. You get the benefit in this case 76 months. That lady is very important. And the important is that not only they included chronic kidney disease from diabetes but they also had about a third of the population. Non diabetic. I mean, these these medications were developed to to treat diabetes right? But now you're seeing other other implications or other uses of it. Very consistent data. Primary composite endpoint significant improvement in the treatment group uh composite of death cardiovascular hospitalization. So see see they had CKD but they they could have had chF decreases no symptoms of chF decreases rate of hospitalization from chF mm. You know, specific outcomes obvious. And this is from any reason it has a mortality benefits. They all do have mortality benefits. Is this does this look familiar? But this is a different medication, very similar GLP one receptor agonists. Let's talk about those. So and um in laboratory studies they showed, first of all, they are present in the video cells and macrophages and also in proximity to GLP one receptor agonists. In experimental models, they reduced albumin urea decreased essential expansion and global based on member and thickness and the failure protection and baby Stuart potus sites. If you remember now Dr Mendieta slides, they were part of the pathology, one of the important parts of the pathology. You sets up again in experimental models. They work at the kidney or agonists are drugs they work at the kidney level. They caused by viruses. They cause natural races. Um They can reduce inflammation that was the goal uh They work at the school tomorrow so that they work in many organs. They work in the skeletal muscle. They increased glucose uptake even fat tissue. Brown brown adipose tissue or white adipose tissue. Um they work favorably there and deliver. They decrease glucose production, decreases ketosis in bowels. Uh The slowdown motility uh which can potentially explain the way they work in terms of reducing absorption of uh glucose at the pancreas level, increases insulin secretion. Um And at the stomach level, they also still down gastric emptying. Yeah. Mhm. Doula Glue tide is one of the most important ones. And awards seven, I would say. It's very striking or initiating discussion about the benefits of uh GLP one agonists in CkD. They studied people with CKD three and four. Uh They gave them either low dose or high dose of uh do a glute tight. And they compared it to uh to a long um acting insulin. Mhm. Uh In this slide, it speaks better. Uh We saw you saw improvement uh in kidney outcomes or no reduced reduction in uh loss of G fr in dolly blue tide. Or interestingly it happened for patients who already had micro albumin urea. So the mechanism is probably better explainable uh from damages of albumin urea software or causes of albumin urea, which is better controlled with glue tight. And that is probably improving the renal outcomes. This just came out uh I cannot even pronounce this one. Uh if legal entity for a pickle and type uh amplitude. Oh um I don't think, I don't think it's FDA approved yet. It just came out in new England journal. Uh The incidents of major advanced cardio, adverse cardio cardiovascular events uh decreased significantly more significantly. I see real composite outcomes with use of this agent. Um And the composite outcomes were all better now when when when it becomes more normal in our routine practice I think it's gonna come out soon. I'm sure there are more studies coming out in this line. Overall GLP one agonist that the major side effect or the major obstacle and using them is is gi side effects. Uh People get nausea, vomiting, diarrhea, constipation and that that falls that that is coming from from all the mechanism of of of these receptors. Um You know working in different organs mostly in G. I. System. Other than that they reduce the help reducing weight, they help producing uh hemoglobin a one C significantly. I'm sure my my endocrinology colleagues have a lot of experience with that patients are just happy. I mean they come back saying that you know I haven't been able to control my hemoglobin a one C for years and now since I started uh this medication for example commercial, truly city. I have no toys. Uh No one really wants to improve significantly. Yeah. To summarize this is a this is a slide from Katie Go which we can summarize all the benefits of S. C. O. T. Two and GLP one inhibited agonists here, both of them pretty much the same level of reduction in hemoglobin a one C. Um in reducing atherosclerotic cardiovascular events. there are similar, they can help uh maybe not hugely sc sc two inhibitors decreases uh no adverse events from heart failure, hospitalization and so on. Uh Not not so much for GLP one agonists in this time. Uh SclC two inhibitors significantly improve albumin. Urea GLP one agonists do that to maybe more SGL T two inhibitors. Uh They reduce risk or rate of G fr loss GsG LT two inhibitors have better job on that. Do a better job than that comparing to GLP one. So uh I think I think this is this is what we should significantly and and seriously consider for our patients. And then Katie Go moves on to Chapter five, which provides guidelines about, you know, self management and team based approach to diabetic kidney disease. Now, here's the algorithm. Uh Life is start therapy is the first line, right, Okay. Diego here recommends starting metformin and sc sc two inhibitors at the same time. Uh we do use metformin freely for patients who have G. F. for more than 45. If it drops between 30 and 45, maybe we need to reduce those of metformin. We don't use Metformin for diana's suspicions. S G. L. C. Two inhibitors uh Are safe. We know they are safe for G.F. are more than 30. Now, one of one of the post hoc analysis. Uh I think it was It was that part if I'm not mistaken. I might be mistaken on that. They studied g fr between 25 and 30. It was still safe. I personally felt nervous about that. But now if it is more than 30 I always use the CLT two inhibitors. Um I'm more comfortable with Farc Siga but you can you can use any of the other ones for dialysis patients. Perhaps it doesn't do much. I don't know if it has any side effects or not, but because they don't have any kidney function. And one of the major site at the CLT two inhibitors are working our kidneys. I don't think it's the L. T. Two inhibitors can can benefit the patient much. So we're not we're not using the when it comes to to to more uh you know, well known or longer time used medications. GLP one receptor agonist comes here then DPP four inhibitors, insulin uh suffering serious etcetera. Um In summary uh patient centered decision making and support and consistent efforts at improving diet and exercise remains from uh foundation of algorithmic management in CKD from diabetes. Control of risk factors including wrasse blockade remains part of the standard care. Uh chrissie MIA is monitored with chemical anyone. See and blue blood glucose. We all know that christ targets should be individualized. We focus on increasing risk of hyperglycemia with declining kidney function. So this is this is something that we may we may consider it at all time. People who have reduced kidney function. They need less insulin there sometimes you you hear from patients saying that no I I used to be a more insulin now. I have had to call you back. They don't know the relationship. Right? So we know that reduced kidney function decreases metabolism of indigenous indigenous insulin. So they end up requiring less insulin. That might be one reason. Um Initial use of metformin and ScLC two inhibitor is recommended at the same time. Healthcare organizations should support a coordinated effort and with that, you know, I thank you all and uh I'll be happy to answer any questions they can. That's fabulous. Thank you so much. Once again, uh Reza and we do have time for a few questions and there are a couple that I will ask you about and if anyone has any other ones, please submit them. Maybe just one thing to start off with. Someone has asked about the use of SGL T two inhibitors and some side effects. They asked about whether there's any hyper Cally mia. I might wonder about hippo kye kelley mia with these ones and then maybe hyperbole mia. Um just how much of a risk is that uh these patients and when we use a Sure, so hyper Cali mia uh is not a significant risk. As you said, if anything we see more hyperlocal e mia usually it's not severe. I haven't seen any significant Typically MIA from from S. G. L. T. Two inhibitors hyper bulimia can be significant Hyper bulimia can be significant. I usually recommend patients to decrease their diuretics if they're on a diuretic when when I started CLT two inhibitors. And as far as, you know, other uh other uh anti hypoglycemic agents, uh if they if they are naive to SCL T two inhibitors and they're already on uh one other class other than Matt foreman, I would recommend to decrease the other class when they are studying SCL T two inhibitors. Those are the major things that I would look at. There was a lot of concerns at the beginning regarding urinary tract infection because these are going to Zurich agents. Uh it has not been substantiated significantly. So uh we are we are not too concerned about that anymore except for uh transplant population if they have history of urinary tract infections. We uh we hesitates joining us. The altitude inhibitors. We usually with a little bit of hesitation for that population immunosuppressive as well, which would put them at any increased risk also. Right. Yeah. Um, you know, maybe just going back to the previous talk or maybe it's part of this one. Just someone submitted a question asking about cece statin C um and do you use that to verify renal disease. Uh Sure, there is an ongoing talk right now in many mythology communities how well or how good is creating as a market for estimating. G fr uh sees stephan C is gaining momentum more and more because uh you know, it's it's well proven now that it has a better It gives a separate estimation of estimated G. four. Uh The reasons are many. Uh not to mention uh no muscle mass in creating comes from muscle people who have higher muscle mass. Uh They generate more creative to begin with. And the computer which is calculating estimate gear for the N. D. R. D. Formula or CkD Ap they don't they are not normalized for muslim mass. They are normalized for an average sized person or 1.73 square meter body surface. Um So C. Seven C. I use them a lot, especially for for patients who come to me with mild CkD I mean ranges of CKD 2 to 3. I once in a while I get a patient who is very concerned saying, oh my creatinine is 1.1. Uh you know, it was it was 0.9. Why is my GF are down to 255 now for those patients that you C. Seven C. Two to make sure that the G F. R. Is is uh in the normal range. Got it. That's great, thank you. Um All right. It looks like we are at the end of our questions here. Um Thank you so much. You know, I think we're beginning to hear a theme related to these newer agents that first came out for glucose lowering and as endocrinologist, we were very enthusiastic about these. But as we are seeing from this morning and from what you just told us, they are rapidly being adopted into the cardiovascular world, into the nephrology world. And it's great to be a team associated with all of these to be able to take better care of our patients with diabetes. So rosa thank you once again so much for joining us and um we'll let you go for the afternoon. But it was, it was great having you on here. Thank you so much for having me. It was a pleasure.
