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Um, welcome everyone. Um As always, please put your name, medical school, year of study and the place you're currently in in the chat, please. Um And when I post the feedback form in the chat towards the end, please do complete that. It's very important for the medical school to keep going. Um, and I'll hand it over to you now, doctor. Thanks very much. Good, good morning. Good morning. Ladies and gentlemen, my name is Kevin Fernando. I'm a G P family doctor in North Derek Health Center. Was just, just near Edinburgh. I was Edinburgh graduate a long, long time ago now. And I've had a long standing interest in diabetes, cardiovascular vineland, metabolic medicine. And that's really the focus of this, uh, this lecture. Many of you might be aware we've had significant practice changing research, evidence guidelines published just even over the last couple of years that have driven a real change in how we approach the management of the person living with type two diabetes and co morbidities in uh in the population. So that's why I wanted to take you through some of the top line messages in water or what we should be doing differently. I'm also Scottish lead of the primary care Diabetes society and I have a rule for Medscape global as well as education role as their content advisor. These are my disclosures. So as always, I thought be helpful to maybe start talking about a patient broadly based on one of my patient's in North Berrick. He's a 52 year old gentleman mail, uh the B M I 31 of a Scottish Caucasian background. No family history of note. And he's been living with type two diabetes over the last six months or so also has a background of hypertension. His current medications, he's on uh Metformin 1 g twice a day which he seems to be tolerating okay. He's on Lisinopril 20 mg, one of these inhibitors for his hypertension and he's on atorvastatin 20 mg for the primary prevention of cardiovascular disease. So he's had some blood checked recently and some other assessments. His current HBA one C is 58 millimoles per mole or 7.5% or thereabouts. His lipid ratio is total cholesterol to HDL ratio is 3.9 BP 129 79. And his kidney function is okay is E G F R estimated glomerular filtration rate over 60. So he works as an architect. He's an ex smoker. I did refer him to Desmond, which is an education program we have in the UK for people who have newly diagnosed with type two diabetes, but unfortunately he didn't attend and he tells me he drinks alcohol socially. So, ladies and gentlemen, the first question for us all here. Just, just some food for thought. You, what might you consider doing next with respect to his management? Would you reinforce that all important lifestyle advice is so pivotal to the successful management of type two diabetes and not make any changes to his drug regimen? Oh, would you add in one of the sulfonylurea drugs for diabetes? Gliclazide, for example, high a glitter zone, one of the Gliptin sit, a Gliptin. Don't worry if you're not so familiar with some of these classes. Are we going to be touching on them and focusing on a couple of the classes, would you add in one of these newer SGLT two inhibitors such as Dapagliflozin, empagliflozin or Canagliflozin or an injectable actually comes in an oral form. A G GLP one liraglutide, semaglutide, dulaglutide. What would you do something else? So, just have a think about that, you know, just to remind you about our case study there. Uh and I'm just going to change the goalposts a little bit now as well. So unfortunately, despite all our hard work and support with my patient corner, he's suffered a non ST elevation, myocardial infarction and had to go undergo percutaneous intervention and he's got a couple of cardiac stents in place. So unsurprisingly because of his cardiac event, his medications have escalated, he's still on his Metformin and the Lisinopril. But now he's on a secondary prevention dose of October statin 80 mg. He's on, buys opera all a beta blocker 10 mg and he's on dual anti platelet therapy, both aspirin and clopidogrel, clopidogrel for 12 months because he has a stent inside you looking at his numbers, his B M has come down a wee bit to 30. Unfortunately, his glycemic control is worse and it's now 60 for minimal Permal or 8% total cholesterol. 3.9 LDL cholesterol, 1.8 BP, 126 74. So remains well controlled and this renal function remains normal. So, same questions. Really. Uh the same question, ladies and gentlemen, but with a few more options, what might you consider doing next? Now for, for Connor again, lower drug changes, lifestyle or sulfonylurea pioglitazone, gliptin SGLT two inhibitor GLP one or would you look at other aspects of his cardiovascular management? Would you intensify his lipid therapy? His current LDL cholesterol is 1.8. Are you happy with that? Would you want something a bit tighter? Would you step up his lipid therapy or would you intensify his anti hypertensive therapy is current BP is 126 74 if you want that titer again or would you do something else? So, just before we move on to the bulk of uh of the lecture, any initial thoughts on what you might do for my patient, I appreciate. Um Is that some of them perhaps may not be familiar with some of these diabetes drug classes or newer guidance, but any thoughts feel free to, to type into the chat box if you have any comments, thoughts on, on what you might might do. So, whilst we're waiting for any comments or thoughts there, I wanted to share with you one of the free resources I've put together with, with Medscape that I've been disseminating via social media um freely available online. If you want copies of this is PDFs. I've got my contact details at the end and this is that perennial challenge for us. And I think you'll find this helpful. Hopefully find it all helpful. What next after Metformin? So we have a comment here. Add another drug to stabilize HB one C good stuff. Any thoughts, what particular drug that might be? Um So this, this is where hopefully you might find this uh to answer this question, this table helpful. It looks at all the major classes of drugs available to us for the management of type two diabetes and goes through the mode of Axion, the glycemic efficacy and the impact on weight, any cardio renal benefits and of course, any side effects we need to be aware of as well. So do have a look at this um in your own time. Uh Then another free resource I've put together is about using these drugs in the context of renal impairment and chronic kidney disease. Because a lot of the diabetes drugs we we use need to be titrated, don't they? In the context of renal impairment to avoid harm? So I put these together to, to, you know, to help my colleagues are in the UK. But of course, relevant to wherever we were studying, working in the world. But really in this session here, I wanted to focus on than one of the newer classes of drugs that S G L T two inhibitor, sodium glucose co transporter two inhibitor. Now many of you may not be maybe not be so familiar with this class of drug, but I know it might sound like hyperbole, but this is probably the biggest therapeutic advance in my career today since I graduated from Edinburgh medical School during the 2000. Uh you can see this is a paper or the headline from the front cover of the lancet. So our highest impact medical journal in the in the world arguably and what the headline of the Lancet said a few years ago. Now 2019 um suggest that SGLT two inhibitors should now be considered as bustline therapy after Metformin for the majority of people living with type two diabetes. Okay. So you can see there's a lot of excitement about this guy, this class of drug and really it's, it's become the new standard of care for people living with type two diabetes. And I'll tell you why the number of benefits. But as always, we need to balance these benefits against particular harm. So I'll take you through some of the side effects of pitfalls to avoid as well. But I suppose the big change that alluded to at the beginning of my introduction, we're now using SGLT two inhibitors. This new class. Don't worry, I'll tell you how they work in just a second, not just for diabetes, but we're now prescribing them in a much wider range of clinical scenarios. So this is another free resource, educational resource I've put together to help simplify the use of these SGLT two inhibitors. Uh And as you, you can see, well, you can have a look at this uh in a bit more detail in your own time, but we're now using SGLT two inhibitors, not just for type two diabetes, but for cardiovascular disease, for heart failure and for chronic kidney disease too. And also interestingly in people living with and without type two diabetes. So, uh when a brave new world really and, and how we manage type two diabetes, we need to think beyond the glucose and look for the presence of significant co morbidities as well. And I appreciate your, your all at the very beginning of your, your journey of your medical career. But as I've told you already, certainly in the 20 years since I've graduated, this has been that this class has been the biggest therapeutic advance. This is certainly the new statin of my, my generation. And I suspect when all of you have 20 years down in your career, uh the use of this class of drug will be commonplace and standard of care for, for the majority of patient's. Okay. So, uh one quick last three resource have put together, this is a non pharmacological resource. Uh We're focusing of course on type two diabetes. But as you know, many different forms of diabetes like one type two gestational diabetes, pancreatic diabetes too. And because of the obesity epidemic, it's increasingly challenging, isn't it to differentiate even between type two diabetes and type one diabetes. And often the safest strategy is to presume type one diabetes until proven otherwise. So have a look at this resource as well. You might find that helpful. Okay, great. So let's go back to basics then SGLT two inhibitors for those of you are perhaps not so familiar with them. So SGLT two stands for sodium glucose co transporter two. Okay. And there's four currently available, a number more, several more in the pipeline. And these are drugs that end with glyph lives in. So can a glyphs in dapagliflozin, in empagliflozin and earth, the blood flows in other, the main ones you certainly in the UK. So importantly, this class of drug works in an insulin independent mode of Axion. It actually works through the kidneys to inhibit the renal re absorption of glucose. So let me illustrate that to make that, to simplify that explanation. So, in your renal tubules, you can see here, you have transporters called SGLT two in your proximal tubule, sodium glucose co transporter two. And this is really responsible for the reabsorption of glucose from the urine back into the circulation. So you can imagine that if you give a drug that blocks that transporter, instead of reabsorbing glucose, you're passing it out in the urine. So that's, that's how it exerts its glucose lowering effect. And with a typical SGLT two inhibitor, you're excreting around about 70 to 90 g of glucose a day. So this glucose has a calorific value, doesn't it? So you're passing out around about 3 to 400 calories a day. So that's why with time this class of drug as can facilitate some weight reduction too. So some secondary benefits of weight reduction. And remember the SGLT two stands for sodium glucose co transporter. So this transporter is also responsible for some sodium re absorption from the urine. So by blocking that transporter, you also have some sodium loss in the urine and that can help facilitate some BP reduction to around about 4/2 millimeters of my mercury. So glucose lowering weight reduction and BP reduction almost sounds too good to be true and it had it is too good to be true as with any drug, as I've said already, we need to balance the benefits against the potential side effects and adverse effects. So that's in a nutshell how this class of drug works. Okay. So an insulin independent mode of Axion. Now, in terms of potency, it's a moderate important glucose lowering agent. You can expect around about 1 to 1.5% lowering in glucose sometimes much higher. But you get your non responders to with the secondary benefits. As a mention already of weight reduction and BP reduction too. And by themselves, SGLT two inhibitors carry a low risk of hypoglycemia of low blood sugar. Okay. So that that risk benefit ratio is favorable in terms of hypoglycemia. Of course, if you're adding this class of drug onto something like gliclazide or insulin, that then that the hypoglycemia risk of those drug classes are of course much higher. So we do need to still take that into account. But really the big exciting uh development with this class of drug are the proven cardiovascular and renal benefit. So over the last seven years now, actually, we've had a series of high quality trials published demonstrating atherosclerotic cardiovascular disease benefits heart failure benefits and kidney benefits with this class of drug. So that's why not only in primary cares, GPS, nurses and pharmacists. Are we using this drug law? My cardiology, colleagues in hospital and my renal colleagues in hospital are also using this class of drug regularly. Okay. And I'll develop an act in in just a minute. Uh So when starting this class of drug. It's very important. We're aware of the baseline renal function because as I've taken you through already, this drug works through the kidney. So it requires an adequate filtration rate in the kidneys to excrete that excess glucose. So, baseline E G F R is important. So uh if you are going to be prescribing this in the near future, do check what baseline EGFR for that specific SGLT two because it varies from molecule to molecule. But what is important all SGLT two inhibitors after Egfr drops below 60 that there's limited glycemic efficacy. Um So you might need to consider an additional glucose lowering drug. Okay, that's the same for all SGLT two inhibitors. So as you'll be seeing shortly, we are now starting them purely for renal protection where and they work the lower and EGFR 60. But if you also need glucose lowering efficacy, you may need to consider an additional drug. So you can use SGLT two inhibitors by themselves or in combination therapy alongside other oral diabetes drugs alongside injectable drugs such as G L P ones and an insulin as well. Okay. So that in a nutshell are all the benefits of the class of the drug. Okay. What are the side effects we need to know about? Well, uh from the explanation I've given you and how they work the best way to look at the side effects of SGLT two inhibitors is a very similar to the symptoms and signs of type two diabetes itself. Okay. So, because you're passing out that excess sugar in the urine, by far, the commonest side effect with SGLT two inhibitors are mycotic genital infections. So, thrush like infections in women, Dallan itis type infections in men UTIs, urinary tract infections can also be a potential issue but much less frequent than the thrush like infections. Uh and because of the diuretic type effect of this class of drug osmotic symptoms can also be an issue. So first polyuria, passing urine frequently through the day or even the night, lightheadedness and fatigue as well. Rarely, occasionally SGLT two inhibitors can actually cause volume depletion. Again because of that directive like effect or even in our more vulnerable patient's can even cause clinical dehydration as well. So just be aware of that certainly in are more frail patient's, we must pay particular attention to that risk benefit ratio. Now it works through the kidneys. Do we have to have any concerns about acute kidney injury? The answer is no um data suggests no signal for acute kidney injury for this class of drug. And indeed quite the opposite, there appears to be perhaps a protective effect against acute kidney injury. With this uh with this class of drug SGLT two inhibitor, we've said for a while, it's not recommended in those over 75. Uh mainly because all the studies that looked at SGLT two inhibitors didn't include many people over the age of 75. But actually, we're increasingly seeing evidence that this class of drug can be beneficial, particularly from the cardiovascular point of view as I'll be showing you shortly. So what do we need to advise patient's? If we're going to start this class of drug, we need to reinforce adequate hydration, good fluid intake, at least 22, 2.5 liters a day. And because of the potential of those thrush like infections reinforce good personal hygiene as well. Okay. Now, there are a couple of specific side effects that you might be aware of that. I have had a couple of UK based alerts and alerts elsewhere in the world. And I just wanted to take you through those two very quickly before we talk about changes in guidelines. Okay. So the first of those is this uh rare but uh potential risk for diabetic ketoacidosis. So in the UK, we have this body, the MHR A which does issue drug safety updates if there any new data comes to light. So we've had a number of drug safety updates about SGLT two inhibitors and their risk of diabetic ketoacidosis. So the first key mess here it is rare. We're talking one in 1000 to 1 in 10,000 and the benefits do outweigh the risks for the majority of our patient's. The challenge for us when using SGLT two inhibitors is that, that, that the DKA we see with SGLT two inhibitors is what we call you glycemic DK. So blood glucose levels are normal or near north normal. So for those of you have seen DKA on the wards when you've done in the past or read about it, typically, of course DK sugar levels are 30 40 50 un recordable. But that the episodes of DKA, I've seen with SGLT two inhibitors, glucose levels are 678, you know, normal or near normal because you're peeing out urinating out that extra glucose. So what should we do then how do we make sense of this when prescribing SGLT two inhibitors? So when we're starting an SGLT two inhibitor, we need to warn individuals about the signs and symptoms of DKA, which is a challenge in itself, isn't it? Because DK is very nonspecific, abdominal pain, nausea, vomiting malaise. So basically what I tell my patient's, if you're non specifically unwell on an S GLT two inhibitor, you need to get in touch for further review. I need to assess that patient clinically. Um And what I need to do is check glucose levels. But importantly, if I suspect DK, I need to go on and check blood ketone levels even if glucose levels are normal because of the you glycemic nature of that DK. Okay. So just be aware of this potential rare association of DKA. So really, this means ladies and gentlemen, we need to reinforce sick day guidance for people taking SGLT two inhibitors. So this is guidance to temporarily stop drugs during any acute dehydrating illness, such as diarrhea or vomiting, etcetera. So useful Pneumonic for us all to be aware of the sick day guidance is sad man, temporarily stop the S the SGLT two inhibitors A for a sin Him, Bitters D for diuretics, M for Metformin, A for ARB such as low tartan and N for nonsteroidals such as Ibuprofen or naproxen. But importantly, we need to remind patient's to restart these drugs once they've recovered from their illness and eating and drinking normally, usually 24 to 40 hours later. Okay. So temporarily stop the sad man drugs but restart them once individuals have recovered and eating and drinking lee normally. And that's to hopefully prevent potential DK with SGLT two inhibitors. Of course, the concern with diuretics, ace inhibitors, Metformin are things such as a acute kidney injury or lactic acidosis with Metformin. But with SGLT two inhibitors, as I've told you already, we're not worried about acute kidney injury, but we do have to be aware of potential DK. Okay. Great. And then the second safety alert we had about SGLT two because is even more rare for years, gangrene. Now, for those of you not familiar with, for years, gangrene, it's necrotizing fasciitis of the genitals or perineum. So pretty nasty and potentially life threatening as well. But incredibly rare. Unfortunately, we've had a couple of drug safety alerts about this, but I think this has been a bit unfair because you're talking of only six potential reports in nearly 600,000 years of a patient, years of treatment, certain uh in the in, you know, in the UK. And actually when you look at all the SGLT two inhibitor trials, we don't see a significant imbalance between the placido arm of the trial and the SGLT two arms of the trials in episodes of this pony is gangrene. So I don't explicitly mention it to my patient's, to be honest, because it would be a real barrier, wouldn't it to starting uh starting an SGLT two inhibitor? But what I do do is tell my patient's taking SGLT two inhibitors to seek urgent medical attention if they get any severe pain, swelling, redness in the genital or perennial area. Okay. So again, reinforce good personal hygiene when starting an SGLT two inhibitor. Great. So that was just a quick overview of how they work. Some of the pros and some of the cons as well. What I want to do now for, for the last half hour or so of this lecture of slightly less to make sure there's time for questions is talk about a change in guidance in how we use SGLT two inhibitors. So in the UK, many of you will be aware, we have high quality guidelines from nice. Um and they drive a lot about our, our management clinical management in the UK. So we had updated type two diabetes guidelines just published last year, originally in March 2022 but updated again in June 2022. So really hot off the press and again, it's driven a significant change in how we approach type two diabetes in primary care. Looking beyond the glycemia. So I'm not saying good glucose control is an important and type two diabetes. Of course, it's very important to prevent against the microvascular complications of diabetes. The blindness, the retinopathy, the neuropathy, but good glucose control really only as a modest impact on the macrovascular complications that atherosclerotic cardiovascular disease such as a scheme of heart disease or peripheral vascular disease. So what this guideline suggests we do, as you can see from this nifty demographic here is to take a more joined up approach to the management of type two diabetes. Yes, look at the glucose, but also look at the presence of significant co morbidities such as atherosclerosis, chick cardiovascular disease, heart failure and chronic kidney disease too. Okay. So, very much this encourages us to look at the whole person and not just the disease, not just type two diabetes. And this brings to mind one of my all time favorite medical quotes you may have heard of, Sir, William Osler, the late great Canadian physician. He famously said the good physician treats the disease, the great physician treats the person who has the disease. So again, don't just focus on the type two diabetes, look at the presence of other conditions, but also uh what their psychosocial factors are, what their frailty status is. Um you know, any significant psychological or site theatric cool mobility as well. So treat the whole person, not just the type two diabetes and that's very much reinforced in the nice guideline. You don't need to read this whole slide. But you can see at the top individualized care, one size does not fit all pivotal to the management, not just the type two diabetes, of course, any long term condition. So I've simplified the guideline into there's an algorithm within the guideline, which is quite busy. To be honest, I tried my best to simplify it. I appreciate this is still a little bit busy, but I wanted to take you through the key considerations when we're looking uh consulting an individual living with type two diabetes. Okay. So at the top bubble, you can see, look at the HBA one C. So look at the glucose control. As I said, I'm not saying good glucose control isn't important. So do assess the HBA one C. What is your target? Individualized HBA one C for younger people, of course, that generally should be a tighter, tighter target to minimize future cardiovascular and micro and macro vascular risk. Whereas for my my older more frail patient's maybe the emphasis is more in quality of life. So we can take our foot off the pedal and aim for a higher HBA one C target. But the big changes here. Nice. Now, also ask us to assess cardiovascular risk and kidney function too. So look at that whole patient, not just the type two diabetes. So starting with that middle column there for anyone living with type two diabetes with a background of either chronic heart failure or atherosclerotic cardiovascular disease. Again, such as s chemical heart disease or peripheral vascular disease, we should reinforce that all important lifestyle advice we should offer Metformin, which I'm sure many of you will be familiar with. But the big change in practice here to reflect all this pivotal evidence about this new class of drug SGLT two inhibitor, start Metformin. And as soon as that Metformin is well tolerated. So even a week or two later add in an SGLT two inhibitor with proven cardiovascular benefit. Okay. So a big change in practice, early combination therapy with both Metformin and an SGLT two inhibitor for those of our patient's at highest cardiovascular risk. So it's certainly a big change for, for many of us, most of us in the UK when this guideline was published uh last year. So I just wanted to outline that, that what's happening, not just in the UK, but across the world in the management of type two diabetes and cardiovascular disease. But nice take things one step further. He also asked us to assess the cardiovascular risk of that person living with type two diabetes. So we in the UK, we use this 10 year cardiovascular risk, calculator called Q risk. And it assesses that person's risk of having a cardiovascular event over the subsequent 10 years. And it takes into account a range of risk factors such as family history, smoking status, BP, type two diabetes status, etcetera. So what this a nice guideline tells us if that 10 year risk of having a cardiovascular event is 10% or higher. We should do the same start Metformin. And as soon as that Metformin is well tolerated, adding an SGLT two inhibitor with proven cardiovascular benefit. So again, early combination therapy for those at higher cardiovascular risk. So, so you can see some big changes are put for us in the UK and across the world in how we manage type two diabetes, looking beyond glucose and also considering the presence of significant co morbidities such as heart failure and atherosclerotic cardiovascular disease. So very quickly, then you can see that SGLT two inhibitors are now a new pillar of treatment for heart failure. Uh interestingly, that's in people both with and without type two diabetes. So many of you will be familiar with ace inhibitors and ARB S or armies. Um These are angiotensin receptor net pro license inhibitors. Uh Sacubitril valsartan is an example of the this drug, key pillar of heart failure therapy, beta blockers such as Baeza prolol, um Mras mineral oh receptor antagonist, such as spironolactone or plenary own. These have all been well established therapies for heart failure over the years. But now, as you can see from this chart, SGLT two inhibitors are also a key new pillar of heart failure therapy. And that's why our cardiology colleagues are very excited about this class of drug. But the excitement for them stems further because SGLT two inhibitors had demonstrable effects in heart failure in people, both with HEF, hef and Hef breath. Now, if you're not familiar with this, I'll explain this very quickly. FRF is heart failure with reduced ejection fraction. So that's where ejection fraction is below around about 35 to 40%. This is what we previously called systolic heart failure. So this is where the pumping Axion of the left ventricle is reduced. You have a dilated placid left ventricle which is not pumping out a lot of blood, okay. Whereas HEP is heart failure with preserved ejection fraction. This is what we broadly previously called diastolic heart failure and this is where ejection fraction is over about 45 to 50%. And this is where you get very stiffened left ventricle, that's poorly contract tile and doesn't fill up so easily. Okay. So HEP F as you can see from this chair is driven by hypertension by diabetes and by the aging process. Whereas HEF rep is largely driven by ischemic damage. So after a myocardial infarction after hypertension as well, and by cardiomyopathy and renal dysfunction to an SGLT, two inhibitors have been demonstrated to have benefits in both Hep and head ref and again, this was from the lancet just last year. I think it was August of last year. So again, hot off the press telling us that SGLT two inhibitors are the bedrock of therapy for people living with heart failure, both with and without type two diabetes. So that's why ladies and gentlemen, we're going to be hearing a lot more about this class of drug. That's why we're going to be using in this class of drug a lot more. So I appreciate there's been a lot to take in already in, in the last 40 minutes or so. But as I've said, a number of times now these I feel are the biggest therapeutic advance in my career today. So I think it's important whatever stage we are in our medical careers that we're aware of the potential impacts on both quality of life and quantity of life with this class of medication. Okay, next, very quickly, kidneys um for the next 10 minutes and then we'll finish up with some Q and A. So I've told you already, my diabetes colleagues, very excited about this class drug, my cardiology colleagues. But so are my kidney colleagues as well. Chronic kidney disease. Another v very common co morbidity, isn't it? Alongside type two diabetes? It's estimated up to 40% of people living with type two diabetes have some form of kidney impairment, be a reduced E G F R or elevated amounts of protein in the urine and very much ladies and then a gentleman chronic kidney disease is an independent cardiovascular risk factor. Okay. And I still love this slogan from World Kidney Day around about 10 years ago, over 10 years ago, now protect your kidneys, save your heart. So, chronic kidney disease is indeed an independent risk factor for cardiovascular disease. People with CKD rarely die of their CKD, do they? What they die of? Sadly, tragically is a cardiovascular event as their kidney function continues to decline. So what do we do for someone with type two diabetes and kidney disease? So again, I've simplified the guidelines here. So for that person living with type two diabetes, if their urinary A cr the urinary albumin creatinine ratio is less than 3 mg per mil. Um oh, that's not clinically meaningful uh proteinuria. But we do need to still monitor there. You Neri A cr at least annually check their kidney function, their creatinine in there. E G F R and their BP again, at least annually. However, if they're urinary A cr is above three or three or above, that is clinically meaningful. A cr and that individual is at future increased cardiovascular and renal risk. So what what should we do for that individual with diabetes? So as soon as anyone you know, rises about three, we should offer them an ace inhibitor or an ARB, an angiotensin uh Tencent receptor blocker. So something like Lisinopril or something like Losartan. And importantly, we should titrate up that to the highest tolerated dose for maximum impact. But this is where there's a big change in practice. Once they're optimized on that ace inhibitor ARB, what the new guidance from? Nice tells us is if they're you Neri A cr remains above 30 we should offer an SGLT two inhibitor independent of the HBA one C. So even if that person with type two diabetes has an HBA one C of 6% we would still offer an SGLT two inhibitor because of the renal protective effects of this class of drug. Okay. And even if that urinary A cr is between three and 13, we should also consider adding in an SGLT two inhibitor. So a big change in practice for as old ladies and gentlemen, for kidney disease as well as atherosclerotic cardiovascular disease and heart failure. You can see are we going to be using this class of drug in a much wider range of clinical scenarios? And again, importantly, in people living with and with about type two diabetes. Okay. So you can see this is the UK Kidney Association guideline. So again, I appreciate the UK based guidelines but they are now making recommendations for chronic kidney disease for SGLT two inhibitors. So you can see at the bottom of this table, we recommend initiating SGLT two inhibitors in those with heart failure without diabetes. But also we recommend using S SGLT two inhibitors in people with a unitary A cr over 25 without diabetes as well. So again, this is a new standard of care for people living with chronic kidney disease after on top of optimized ace inhibitor or ARB therapy. So, big change, ladies and gentlemen, a foot. Now, these are UK guideline. I've told you already what's going on elsewhere in the world. Well, these are, these are global guidelines for chronic kidney disease. Um K Daigo kidney disease, improving global outcomes. But you can see and this major global kidney outcome again, SGLT two inhibitors as I've highlighted are a key pillar of CKD treatment. So it's not just nice in the UK guidelines across the world are changing. This is another very useful and pragmatic guideline. It's a joint American and European consensus on the management of hyperglycemia in people living with type two diabetes. And again, I appreciate the slides quite busy. But what it, the algorithm in this consensus tells us to do is to look not just at the sugar, but look at significant co morbidities. So you can see on the left hand side of this slide, look for the presence of atherosclerotic cardiovascular disease of heart failure and chronic kidney disease as well. So, a big change in practice, ladies and gentlemen, for us to think beyond glycemia. But as I've said at the beginning and several times since no drug is without harm, we need to always bad balance the benefits of any drug we prescribe against potential side effects and adverse effects. And this brings me to another one of my favorite medical quotes by Paracelsus. He was a Swiss German Renaissance position and the founder of the discipline of toxicology. And he famously said poison isn't everything and nothing is without poison. The dosage makes it either a poison or a remedy. So, yes, I've told you about the compelling benefits of SGLT two inhibitors. The glucose lowering, the weight reduction, the BP reduction, the cardio renal benefits. But I've also told you about the adverse and side effect profile. And this is another prescribing tool that with my colleagues and myself are published in one of the medical journals called Diabetes Therapy. Again, happy to share this with you. If you find it helpful, it's available for you if really in the public domain. And it looks it takes a traffic like approach to prescribing SGLT two S. So the green scenarios are where the benefits clearly outweigh the risks, the amber scenarios where we perhaps need to take a pay a little bit more attend to that risk benefit ratio. And the red scenarios are aware the risks outweigh the benefits. And AKI AKI red scenario is type one diabetes. So currently, excuse me, SGLT two inhibitors are not licensed for use in people living with type one diabetes because of the greatly increased risk predominantly of diabetic keto acidosis DK. So just be just be aware of that. So, coming back to corner then, what, what did we do for? What did I do for Connor? Remember he had type two diabetes. But that's sadly he suffered a non ST elevation myocardial infarction. So he's secondary prevention now, doesn't it? So he's at high risk of a recurrent cardiovascular event. His HBA one C is also high. His B M I is in the obese category. So an SGLT two inhibitor would be a good option, wouldn't it, it would hopefully help bring down his glucose level and his renal function's fine. So we're still getting that good glucose lowering effect. But importantly, it will help mitigate some of his future cardiovascular risk because he, he has both type two diabetes and established cardiovascular disease. And we know past studies for SGLT two S such as some of you may have heard some of these emperor egg outcome uh such as the canvas trial program have demonstrated significant reduction in major adverse cardiovascular events with SGLT two inhibitors. Well, I haven't focused on today just because that time of course, are the G GLP one receptor class. Now, some of you might have some familiarity with this class that these are, this has been a predominantly injectable class of drug, but we now have an oral version and these also have proven cardiovascular benefits. So that's another potential class of drug we could consider. So that brings me to almost then. Now just to finish back with that free resource. I put together about the use of SGLT two inhibitors in a range of different clinical scenarios. So as I said, we're not just using them for type two diabetes. Now we're also using them for heart failure. Both hef hef heart failure with preserved ejection fraction and hef breath, heart failure, reduced ejection fraction were also using them for chronic kidney disease as well. And also for overall atherosclerotic cardiovascular risk reduction. So it's a potentially confusing landscape for us because particularly at the moment, different SGLT two S are licensed are slightly different things. But give it a few years. Ladies and gentlemen will be using once they start to be generic, will be using these molecules interchangeably like we do with statins and with ace inhibitors and the ARB because it is a class effect with SGLT two inhibitors in terms of argue renal benefits. So I think I'll finish up there that leaves me with about 10 minutes or so for any questions or comments. Thanks for listening, everyone. I hope you found that helpful. I appreciate there was a lot to take in there. But as always, I hope you took away one or two messages that perhaps make your life your study a wee bit easier, but ultimately help improve the lives of our patient's. So any questions or comments that come up after today, feel free to email me, Kevin Fernando at doctors dot org dot UK or for those of you active on social media, I'm on Twitter and linkedin as well. So, so thanks for listening. Everyone. Happy to take any questions or comments. I've got a question. Uh Doctor Fernando, uh um uh we're uh starting somebody on SGLT two S D L P to um how often we should be monitoring their blood sugar other than the HBA one C, do they check their blood glucose daily or every meal or how does it? No, no, no, no. So there's no because SGLT two inhibitors by themselves carry a low risk of hypoglycemia. So there's no routine requirement for mon itself monitoring of blood glucose. So, uh you know, most days I'm in practice, I'm starting an SGLT two inhibitor. I'm the lead for diabetes. So I'll, so I told you at the beginning of the good personal hygiene, the sickness rules, but there's no need to routinely blood check blood sugar. So if I'm starting an SGLT two inhibitor purely for its glucose lowering benefits. All I'll do is simply read, see in three months time, I don't ask them to check on a day to day basis. Okay. So if someone develops DK with euglycemia, uh you know, we have to go to the Sad Man process, but it's likely to go into hyperglycemia after that. Yes. So yes. So potentially. So again, give that sick day guidance. So I'll start the SGLT two. I'll reinforce good personal hygiene and I'll tell them if they are unwell with diarrhea, vomiting or just non specifically unwell, seek attention from your, your your doctor or nurse. So if someone and you know, plenty of patients come in to see me on an SGLT two unwell, so what I do then not the patient, what I do is check sugar is normal or near normal. I'll go on and check blood ketone levels because of the you glycemic nature of the D K because the glucose levels are often normal or near normal. But we don't need to routinely issue blood glucose testing strips to someone only on an SGLT two. Obviously, if they're on insulin as well, they should be testing, there will be testing their sugars already. But if it's just an SGLT two and Metformin, no need to issue blood glucose testing strips. Okay. Thank you. No problem. So there's one question here from Mohammad. Would SGLT two inhibitors increased risk of uti because of glucose urea? Yeah, absolutely. But the initial study suggest UTIs would be a major issue. But actually in in further studies and in my own clinical experience, UTIs are very rare to be honest with SGLT two inhibitors. But what is definitely more common is thrush again because of the glucose urea. So I reckon probably up to a third of people, maybe, maybe or one in five, maybe I have people on an SGLT two inhibitor will get some evidence of, you know, thrush or something like that, but it's easily treatable, topical antifungal creams, plenty fluid intake. And to be honest, even if I mentioned this is a risk thrush or balanitis. As, as soon as I say that magic praise this drug might help you lose weight. Patient's are really keen to persevere with it anyway, so I I haven't seen those side effects as a barrier to using this class of drug. Great. Any, any other questions or comments? No, no further questions. Okay, no problem. So no, thanks for listening, everyone. You've got my contact details there. So as I said, more than happy for you to email me uh on social my social media channels, you can find all those resources or feel free to email me directly, contact me directly. And I'm I'm happy to share those three diabetes resources with you to help you your diabetes training. So thanks again everyone and maybe see you at a future future diabetes lecture. Thank you very much doctor. Um Thank you very much to anyone who's um who's still here, please. And if you haven't done it yet, please do fill in the feedback form. Uh It's very important for us to continue the medical school going. Um And we have our next lecture in two hours. So at uh at two PM. So we have a bit of a lunch break. But yeah, please do the feedback form and we'll hopefully see you in the next lecture. Thank you very much correct. Is there anything else you need from me?