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well, everyone and welcome to the weekly medical longer bleep, webinar, Siris and thank you so much for joining us today. We're going to Teo talk about medications and diabetes, which is a very important topic for or carry left one's and one's to be. We're going to be joined by Dr Anjelica Shama, who's going to tell us about it. Make sure he posed any questions you might have in the Commons books on the Facebook event, and we'll make sure downside, um, at the end and feel free to post any picture. Any questions? Did mind BLEEP email address or just ask her to the website? We're happy to answer any time the session is going to be recorded. So if you'd like to have access TV the continent, please make sure you sign up for the future. Webinar ease You feel in the feedback for him, which we're going to Thio and posted QR code for Eddie end on down. You can access with materials on. Also, you get a certificate for attendance on do um we will get old information that we need to make the future serious better so I would fight for to do I'm going to hand over to Doctor and Jack Osama, Everyone thinks are the instruction. Some one of the FT's at the moment, I haven't interest in end of crime. Did my B s e n n different. So today I'm gonna be talking about medications in diabetes. Um, So what we're gonna cover is a bit of an overview off pathophysiology behind diabetes. We're mainly gonna cover type two diabetes. We're gonna have a look at the medications that we use currently on where the awfulest fit into the pathophysiology on, then looking more into the risk and benefit profiles off these options and having a local er exactly how they they work and where they work on also a review off guidelines. I'm briefly then gonna touch on incident therapy. I'm in the context of management of type two diabetes s. I said, if you have any questions, drop them in the trap and I've also got a couple of questions and cases. Eso please make sure you get involved. So starting off where the pathophysiology now, as you can see from a slide at many organs, are two interplay which cause increase in blood. Rico's, on which are underlying the pathophysiology off diabetes. Now in type two, we know that there is impaired incidence, secretion and potentially a loss of B cell mass. But actually, predominantly there's a resistance in the periphery of incident on. But that's why we have adipose tissue involved. We've got muscle as little muscle involved on. They are all under instant resistance, so they're not able to act with the insulin that's there on. We've also got the involvement off the liver, Um, on the gut on. We'll see later how each of the medications fit into each of these organs. Now, before I go into the medication side of things, I think it's literally important. Understand how we actually monitor the effects of these medications. So you've probably heard off HBA one C. So this is our value that we used to see how well, um, patient's glycemia control is over the previous three months. Now, recently or not about recently any more, the units of HBA one C has changed. So previously we were using scented years on DNA. We're using these newer units, but typically at a threshold about 6.5% or 48 most Permal. That's our diagnosis or diabetes. Um, but as we go on, we then use HEB hgb a one C for monitoring, so we set patients individualized targets on. We use these to think about when we might need to add medications or to think about if the medications that we've added are actually working in terms of individuals were type two diabetes and they don't really need to do much. Self monitoring is that you don't expect them to check that blood glucose levels out in the community there. There are the exception. So increasingly patients and even to be on insulin to control their diabetes. And in this group, we would expect them to do their own blood glucose monitoring. If patients are prone to have hypoglycemia, Um said this could be due to one of the medications we've started them on, or it just may be on them physiologically on. We want to keep an eye on their blood glucose levels in the community, and if they're someone who drives lot, so we've got HDV drivers if they're working on a patient, is operating machinery things. That's the kind of people that we would be a bit more road about, I would want them to monitor at home. Now we know that previous studies. So we've got the UKPDS and D C C T. They've shown us to actually best HBA one c Control is really the cornerstone for reducing the micro and macro vascular complications off diabetes on with every percent drop. There are massive implications for these end comorbidities and complications. So, as you can see across ALS, different sectors. So we've got amputation. So in terms of diabetic foot disease might congested these heart failure. And even in my psychology, vascular risk factors on similar results was shown in the DC CT trial. Ondas you can see with every increase percent or 1% of HBA one c got a great increases in these capabilities. So it is really important to fakes. Um, so I've got a question for everybody. So we've got missed a see 68 62 year old sending her annual diabetes appointment on her later stage 31 c was 75 which is about 9% in terms of conversion. Um, the question is, what average would be his level? Would she week sort of running out in the community in the past three months. So if we did give her themselves between two dio what would what would it kind of be? Where would it be? Up? Any one place day is the better deal. A sorrow, maybe. Okay, so I'm just reading the chart stories. I go along, um, so 10 to 14. 15 to 2010 to 15. So that's cool. I'll give you a form. You know, basically, um So Okay, so this is a bit of formula. Basically. So average plasma glucose over the last three months is two times the hatred a one c incentives minus 4.5. So a lot of random figures, but kind of useful. So you know that she's running about 13.5 in the community. And as you can see from this diagram, you really need to have this type control. And when we say about figures until control, really, you want it to be somewhere between 7 to 9. If you're aiming for quite stringent control on de knee thing, sort of in the eleven's and the 12 that's going to really increase your hatred a one C. So it just gives you a bit of an idea of what's actually happening when we're looking at these hatred one C readings. Now we've come a long way in terribly. He's We're very lucky that we have so many options that we can use. And so, um, the options that target or different underlying pathaphysiology it all started off back in the 19 twenties. Thanks. Toe him best in the dog. Um, neighbor prize winning for Discovery. Insulin. We then moved on. We've got two in sort of the 1950 sulfonylurea is on metformin on. Interestingly, they're still, you know, one what Two of our top drugs that we choose right? The beginning. So metformin still very much first line in the guidelines on gone, so in your ears as well. We then went through through the sixties seventies eighties. We've got more trials coming up. Then where Loads of more population of patients With studies on tense, we could really pinpoint the need for strict targets on. Now we're getting into sore serves thousands 20 tens. And that's where you get your cluster off medications. That sort of all sound the same. Um, Andi, Now, sort of coming into the 20 twenties, we're learning a bit more about them were going through sort of second generations of these drugs. We're learning a bit more about there. Risk Profile's on. We're now able to specifically target these medications to patient groups, so we've come a long way since the 19 twenties. Um, it's about the goals of the treatment. So I think and I've mentioned this because we are so lucky and we have a variety of medications were really able to address the needs. The preferences on the top rinses off all of our patients, so we're able to have a look at the risk the side effects the contraindications and say, You know, this would be perfect for one individual, but actually this'll wouldn't be so great for the other on. I mean, it's a good thing because more and more now, patients having increasing life expectancy, we're seeing more co morbidities onda a complications of diabetes as they live longer. So to have drugs that can actually modify this for a very lucky stage. Um, obviously, we want to optimize. I seem a control as much as sport and where on guidelines tell us, um, vigor. So you would have heard HBA one C targets and sort of 7.5% is when you added on drugs or the aim off kind of 7% of a good level. But actually, we're moving towards making these targets a bit more unique because you wouldn't really. You you may not want such strict targets in the elderly. Population on day shift may have their own wishes and concerns about their condition. Um, obviously you want to reduce the employees and complications. So the microvascular in the macrovascular complications on D increasingly now these drugs, they're helping us to do that on the new trials. They're telling us more information on the underlying mechanisms. You may think that actually, the main problem is the high levels of sugar. But actually hyperglycemia comes with its own set of morbidity and mortality. Exceedingly in that the elderly population, it's sort of, you know, one of the causes we will do our 80 a, um, on a hypoglycemic your bank and cause fools it can cause, um, Weston confusion and, um, in the elderly. So that's something that we want to try and avoid as much as possible. So I brought back that diagram, and as you can see now where the medication I'm gonna talk about kind of fit in. You can come back to that, but just a zone overview. You can see that they all, for one, have different targets, obviously lead into the same end goal of trying to lower blood glucose levels. But they also have positive side effects in a way. So, um SGLT two inhibitors. Although their main mechanism is to reduce the glucose reabsorption, they have side effects or improved cardiovascular outcomes on getting me. So we know protective mechanism Onda. The other topic is weight. So this diagrams color coded. It tells us sort of the impact from weight on disses a big thing for our patients. So some will have gone to appeared of weight loss to try and get instance with their diabetes and improve their estimate control. So if they've just had this bit of weight loss, you may not want to start something that's going to cause him to gain weight again. Or if someone is typically obese on, they would like to lose weight than it would be sometimes counter for it and productive to start them on something that would cause them to gain week. So these are the kinds of questions that we ask ourselves when we're starting the medications. Um, and this is sort of a diagram, and you'll probably have seen this before, but it's things we think about when we're starting medications, and I think it's really important because it really high interims. So sorry. I think we're having some technical difficulties, which we're going to still tight in just one second. Apologies for that. And nothing. Angelica's having some pictures of her Internet that she's going to be less very shortly. Yeah. In the meantime, if you can think of any questions that you might have, um will be happy to answer down or later. And so there's anything safe. Are they like to ask a bite? You feel sleepy? Placed in the champs, right? Wasn't back with a story about like, I need, um, everything back to where we were. Sorry about that. Um Right. Okay. So I just carry on on from where I was. Sorry. Um, mild panic. So this is basically just on approach today. Hyperglycemia, um, Andi moving on. So, in terms of the guidelines, the guidelines are quite complex. There's a lot of guidelines from different organizations that in the UK we've got the nice guidelines that then we've got the American guidelines as well. Eso I've chosen sort of this flow chart to use essentially the first line. If metformin is allowed as metformin on, then we monitor and then we can add in the various drugs on def metformin, sort of contra indicated. Then we can start on a different pathway, which will go over but for an overview after we've gone every through everything, this would be a good flow shot to use, um, now finding the best combination of therapeutic age. And it's often trial and error fall for the number of reasons I've list it on. If patients has started on something, we monitor them closely because we want to track the side effects on. We repeat the HBA one C levels because we won't see if it's actually having a good impact or whether it's actually helping us to reduce this or whether, despite the therapy, it's just staying high level now. Novel agents, as I mentioned, allow us to not only target the glycemia control, but also the endpoint complications on the risk factors So that's why in this diagram about a CVD basically means cardiovascular disease and CKD in those individuals, we may want to go to those agents quicker thumb When patients that don't have these called comorbidities Um, now this is another curve that you might see quite often. So it's the Dixie when using oral agents. And as you can see, if you just change from one drug to the other, you sort of get this pattern and flattening on. But then, if you stop adding drugs on therapy, then you would hope that over time on that would that's what's really going to help bring it. Bring down the HBA one c levels on. There's definitely patients who are on three medications on their control is still not where we want it to be. And I'm in GP right now. When you're kind of looking at the drug history like okay, I'll try to increase this one, but if they're all on the maximum, then really you're heading towards insulin therapy. So there are patients where it's very difficult to control their diabetes. Despite multiple management, he right, so kicking off, then the first one, the one we've probably heard most about comes up everywhere is metformin. The class is the Guan I'd say on it has a mechanism of action in three areas, so main action is in the liver where it will decrease least the particle canoe genesis um, decreases glycogenesis is and also fast, fast. Since there's in the intestine, there's been some promising studies which house it to increase the increase in infection. We'll talk about that, but mawr on also helping us with being intestinal microbiome in the bacteria that can potentially eight effects on glucose homeostasis on metabolism. Um, there's also some action on for for insulin resistance down in this little muscles as well. Um, now we know so much about metformin as you saw on the timeline. It was one of our first agents really after insulin, so we know a lot about it's risk profile on that side effect profile With weight, It's weight. Neutral is very good for patients who are kind of a TIA upper limit off their wage for sort of in the abuse category. The way it works, it doesn't really cause any risk of hypoglycemia, so it's very nice for elderly population. They don't have to worry about that. Side effects andare studies the UKPDS. The large scale studies do show that it is good in reducing our end points in terms of some lipid side effects. It does help to limp there, decrease, um, triglyceride levels. But actually, it's probably not the best. If you're trying to work on lipids, the commonest side effect really, and patients will come back with. This is the GI I side effects. So kind of your diarrhea or nausea or cramping pain on. Do you know these can be really debilitating for patients? And that's why we try to up trait titrate metformin. So we start them off on a low dose for a couple of weeks, so sort of 500 mg and then you might increase that on. The maximum dose is about 2 lbs today, So that's that's sort of your upper limit with this medication. If it's still not controlled at that point, that's when you would consider doing therapy, um, other sort of side effects. These may come up on exams. We may see it in clinical practice, and that's been B 12 deficiency, um, the big one sort of lactic acidosis. Although the literature says it's more rare than we may expect it to be on be in keeping with the lactic acidosis. If a person is dehydrated or has had contrast, it may actually precipitate an A k I, um, Terms of contra indications so have to monitor patient's renal function. And actually, that's true for most of the medications. So when they're coming in for their page a one C levels at the annual checks, you want to make sure that you're doing the user knees it can. So it's contraindicated in, and he sort of metabolic acidosis because of its impact on that lactic acid. Um, there's again this caution in heart failure City. I've got a case. So Mister Brown is a 62 year old gentleman has got Type two diabetes, doesn't really know what he's on, but he knows he's taking that for men. He's got a scan coming up, So ct abdomen, pelvis. With contrast his, um, Jeff as 40 when you tested it, um, so does anyone want to sort of right? Any advice they may give him in relation to his metformin therapy before his upcoming scum just post on the chat? If you have any ideas, or if you come across this for okay, would just move, but well, I'll tell you about It s so basically, there's quite a bit about metformin on contrast. So on day of went stop, it went to restart. So in this gentleman, we said his me Jeff, I was about 40. So, really, you'd want to be stopping it about two days before his gun on then, um, Reese thinking about restarting it kind of two days after the scan. In the meantime, you can encourage patient to drink plenty. This is elective, so it's kind of in the community. But if they're in hospital, you may also consider um, IV fluids to prevent the contrast induced neuropathy. So got another case that I'll give you a couple of minutes to read is, um and I think that might be a little bit of a lag. Um, sorry. Didn't if you even see the child? Just put a letter in that. Be fine. Just pick a letter here. So someone was gone for c t o add glipizide. Um, some will take us to see cool. So most people are going see, so I'll just go through them. Um, the thing with this sort of scenario is this risk or osteoporosis? Um, um, we know that in patients who are taking SGLT two inhibitors and people are saying it can actually, um, increase the risk off most process now, the reason why it's no black aside is because it says she's quite frail looking woman on, but she lives alone because she's got this back almost approved. So she's had a fracture recently. It's just that gliclazide maybe state sort of hypos in this lady and with her background on high fracture risk, um, if she did have a fall, that could be pretty faithful. Um, and that's why, in her scenario, potentially DPP four inhibitor might be more safe. So that's why in this lady may think he so we've got to sort of be people pee four inhibitors, the's of the class drugs They go by the ending of gliptin. So these are leaders Lipton on seasick. Lipton on, by the way they work is there's when you have food and the joy tract was a release or what we call incretins, including GLP one Onda. Typically these are broken down by the enzyme DPP four. But actually having levels good levels of GLP one can increase the production of insulin on it can decrease the production of glucagon. So, therefore, is very helpful in reducing blood glucose. So the way that gliptin is work is they try to inhibit the enzyme, which would inactivate thie GOP one. Um, Andi, these are great because they're weight neutral. They don't have any risks of hypoglycemia on generally. If you look at sort of their risks status and the list of sort of risk that come with them, they're pretty safe. So majority of patients should be fine with sort of dipped in therapy, and they have a good impact. With lipids, they can decrease the triglyceride levels. Another good thing, but patients like and helps with adherence to medication is that they're once a day dosage. Um, trials have shown, though, that they only reduced hatred. One c quit very slightly, perhaps less so than the other medications that we have on offer, um, on studies, abortion stroke that they don't actually reduce our major in points and cardiovascular endpoints a Z much has been might want. Um, there's other anecdotal reports in the literature that they may increase the risk of pancreatitis. And so, if a patient has had a previous episode off pancreatitis, it's kind of best avoid these on but can cause arthralgias. So aches and pains of your patient comes in. Um, you started them on a gliptin the essay. You know, I've got joint pain that's horribly one of the side effects, but generally speaking, they are quite good and quite suitable for most people. But it is a shame that the reduction hate to be one C is not that great. Um, now lean a gliptin is hepatic excreted. Um, therefore, you don't really need to adjust it for renal function, but see to get 10. It's been a long excretion, so you do need to alter the dose, but again, quite easy to use any once a day. Right? Um, so then we've got a HD be drivers. Come in. Um, he was diagnosed last year. He's tried about weight loss. He's also on metformin, which is working, so he's managed to come down on the HBA one C. Um, and the question is sort of what would be the next suitable step, so I'll just wait um, so you just type really a letter. Have a guess. Um, but again, just be thinking about in the sort of individual what we would want in terms of their weight and things. Lots people going for be so making no changes and the other intense. Okay, Most people saying not to do anything, One person's thing on glipizide. Okay, so it's been being making those changes and having direct side. Um, now it is really good that he's managed to produce his hatred a one c so that's really positive. And obviously the weight loss on the metformin and the combination of that is working. But if we look at targets for these hatred, one C, we would expect, but it would be sort of 7.5. And if it is kind of over 7.5% or 58 millimeters per mole, you would still want to add in another medication because although it's really good, it's really good. We can sort of get a bit more tighter control. So, um, then adding sort of exam it tight, we would that's kind of ah, third line, fourth line medication so we could start with something a little simpler, Um, problem with big beside, as the previous question is sort of a gang hypoglycemia. We know that he's a hatred TV driver. So if we put in an agent causing hypoglycemia, it could be at risk and then would have to do some self monitoring and things insulin. That would be so soon. That's kind of our end game. And that's when we've exhausted our other drugs. Um, so in this case, something like here. Just so you know, at least out of this, um, sort of S p a p English. So might be the best best option for him. Um, so the's are another good drugs. So I is Ali Dindane's or teas that d s. So these are the details. Um, group on one example is play it pioplitazone. Um, and these work by the by the mechanism all PPL gamma. This is a receptor. It's found in an ad opposed to shoes. Little muscles on. It impacts on. It helps us by reducing with for for insulin resistance. So in the other place since little muscles, um, Andi, it's excreted by the liver. So it's quite good in patients with renal dysfunction um, now there's it doesn't really cause any hyperglycemia again. It's once a day administration on. It does actually have a good impact from our lipid profile so it can reduce triglyceride on in trials. It's also shown to reduce the, um, cardiovascular employments. Um, but one issue with this group of drugs is weight Game on. This has got two modalities. So one is, um, the lipid accumulation. It can deposit into the dip a site so that can increase weight gain. But also it can cause fluid retention. On this side. Effect is thought to be beings driven, so the the higher dose is the patients were on, the more likely it's going to impact. Um, it can also kind of lead to things like bladder cancer, and that's kind of a novel link, but it is now coming into guidelines on. But we've been sort of told that if you have a patient who's got bladder cancer currently or has a background of bladder cancer, or even if they've got macroscopic immature ius. So if someone comes into GP with hematuria on there on prepared your stones, that's when you would think that you know Billy to stop that medication, maybe switch it to something else. Um, now, as we mentioned in the prescription, it does have this link to osteoporosis. So it's been shown Teo be involved with bone resorts Shin on. It can increase the risk of fractures. So again, always looking at the patient as a whole and all the co morbidities really helped when siding Which of these medications to use, um, again, the contra indication of been a sort of a heart failure in bladder cancer and also just microscopic hematuria, which later may turn out not to be better constant. But at that point, you don't know. Um, so we start off on the low doses, and then we can up titrate. We always monitor for complications. So then if patients do come in with kind of fluid retention and things, we can cross the early and switch the medications. So another case then give you a minute? Yeah, just against picker. Pick a letter defeat. Yeah. Okay. So I think for this form, the majority have gone to see um and yes, that is correct, because a side effect or sulfonylurea is waking. So unfortunately, due to the glipizide, this man's put on weight. Eso sulfonylurea is another class of drugs. They're also known as insulin secrete a box due to their impact on. But so what they do is they closed the P channels on the beach cell membranes, they that's mediated through the S. You are one Septra. This'll causes depolarizations in the cell causing calcium influx on, um, the main way that these work is by increasing the release of insulin. So now, because these have a direct impact on instance aggression, these are high risk for hypoglycemic events, and you can see the mechanism there on the diagram. Now, these are one of the early drugs as well that would developed in 1950. So we do have a good profile for these two quite rapid acting on. They also, um, involved in reducing our micro vascular risk factors. So that's been proven in the previous trials. Um, now, in terms of breast, they can cause hypoglycemia up, but also, weight gain on this is quite worried for some patients who may not wish to gain weight and actually in a way but in on that weight may then cause more risk on, but it may not improve their glycemia control overall. Um, and it's reported in the studies that actually over sauce three years, patients can push on up to 3 kg. But the effect of that will depend on sort of the person themselves and their weight a baseline. Um, now, because these work in terms of sort of stimulating the beach cells produce the extra insulin, Um, over time, they actually may become less effective because over time we do know that the be to sell. These is ability to create the extra insulin. So if it's then exhausted on, do you know there's no more insulin? Then you may find that someone's been quite steady on this therapy over a long period of time. But then suddenly that I seen that control is by zing from it can also cause a side paged. So that's one of the side effects on. But there's been some reports of college states. There's, um, central involvement with deranged liver function tests. So if someone is on self in your ears and just keep an eye on their lefties, but these ones, these are quite more of the rare side effects, the ones that you will see firsthand the kind of the labor ship is on the weight gain. Um, not too many contraindications s o. There's a potential that they may contract. And patients with sulfa allergies may react badly as well. Um, so and there other interesting thing is, but they don't seem to have a dose related relationship to the HBA one c. So increasing the dose of the drugs doesn't necessarily mean that the HBA one C is gonna drop further. So you can just see how it how it works for the individual patient in terms of the side effects when you're treating. Okay, so this is the next okay, is say this one's This one's a picture. So it's a 65 year old man is coming with the onset screwed with pain and swelling. Extra points for kind of saying the diagnosis. This is well, if well, what? This shows? Um, yeah, so? So I don't say something about their diagnosis. Correct. Say cool. So, yeah, people got this one right. So s Oh, yeah. Well, don't. The correct diagnosis is for years. Gangrene on. This is sort of a new kind of side effects and complications that we're seeing with patients on dapagliflozin SGLT two inhibitors. Um, so, as you can see, it's sort of a neck try zinc arthritis and has gangrene there in region off the external genitalia. Um, various factory bacteria involved with this on essentially blood sugars are elevated. Can impact on there. So in one study, 46% of patients that actually had for years had elevated blood glucose levels. And this is not sort of the way you want to be told. Um, you have diabetes. So, um, this is kind of a straw thick, um, complication and could sometimes be a presenting feature off type two, um so, so deeply First co transported to inhibitors. Other gift. Lezin. So we've got stop it flows in m heard of lays in on day canagliflozin on Essentially, these are kind of the nuclear kids on the block of the moment, so there's lots of lots of trials because they have found of benefit in heart failure. So using these drugs in, even in patients without diabetes has a major impact from reducing the employees from heart failure. Um, now patients it with type two. They have a it's number of the SGLT two transporters within the renal system and especially the proximal tibial, Um, Andi. So the glucose reabsorption is actually increased from the filter, which is not really what you want. You're trying to reduce the glucose level s so therefore, if we inhibit this transporter, then we can cause, like, a serious so absolutely coast in the urine, which then would reduce the Enbrel. But blue coast, Um, but their mechanism of action doesn't sort of been there, So obviously we know that they have this impact on on the glucose side of things that they also help with sodium excretion on that's really useful were patients who may may be at risk of fluid overload on also patients that do have heart failure. Onda other intervascular issues. Um, they're also be no protective, so they can reduce albumin urea on. Also, they can actually maintain the Jeff are individuals with diabetes. So not only do they work with Lupus, A missed A says and juice. Um, and I seen that control. They also have many of the downstream effects. Where, which are you schooling? This population, um, so sort of the summary. In terms of benefits, they can help with weight loss. So, as I mentioned previously, they prevent fluid retention and fluid overload. There's not really a risk of hypoglycemia. They do cause a reduction in the cardiovascular endpoints that renewed protective, um, that post of facts on the kidneys or SoMa Jesus, BP. And these individuals, um, on there again once a day administration. Um, but they do come with their own unique risk factors. So they do cause an increase in the risk of beauty eyes. They can cause an increase in risk of genital infections. A thrush, um, A Z mentioned for me is gangrene. There's some studies that show that certain types of one of them canagliflozin can actually increase the risk of amputations. But it's difficult to tell in these studies because we know that diabetic foot disease and is one of the one of the complications. So it's difficult. So what impact that sheltie to actually have on that, um on. They haven't think they have an increase in the risk of something called you by. See Mick DKA wish I'll ask you about in a second, um, so sort of contraindications is that if a patient has had DKA or I'm suspecting decay on any kind of setting. Then you should discontinue the SGLT two s because they can precipitate it further on if you have a patient who you perhaps started SGLT two inhibitors on, but then they do go on to experience DKA on a new later, find out. You know, they've been admitted for it. That's when you shouldn't be using them in that patient population. Um, on they are real excreted. They do have an impact on the renal function as well. So you're a bit limited on the patient population if you have patients with CKD, Um, and these are against is some real theat salute contra indication in terms of the Egypt bar, a sort of below 25. But anything below 45 aspirin that nice guidelines is you know, you probably want to choose something else. Um, so this is kind of why I was touching on early s is a conference going on at the moment on basically empagliflozin, one of the drugs has shown positive impact on cardiovascular death and heart failure in patients with and without diabetes. So now there's kind of a move that you may see these drugs in patients without diabetes who have heart failure because they have shown it positive impact on on. If you do see patients, sort of with the maintained e jafar kind of over 45 on, they do have a kind of heart failure on specifically with a preserved ejection fraction with type two. Then this is one of the agents that sort of new and shown quite promising effects. So in terms of this mechanism, So this is medicine that SGLT two inhibitors can precipitate you going scenic DKA. So I've seen a couple of patients with this, um, individuals with type two you don't really expect to see from a d e k A picture. Um, but does anyone know why these might precipitate there? Okay, it was a laxative weight. But, you know, if anyone wants to suggest anything or something, they may have read to, um Well, now we will know. So these these are a couple of diagrams which is quite useful when looking at the sort of mechanisms. So with the SGLT two inhibitors, as we said, they reduce the insulin secretion. Um, interesting Increased the political secretions essentially this Concordes and increasing like well says on. But the free fatty acids, which can then septate key to Genesis on this is more so when that they're safer ones on SGLT two inhibitors and they become on well because because of source of lack of the insulin, it drives further life policies and then generation off these ketone body's. Actually, the sugar levels themselves will probably, you know, won't be as elevations you would expect on. But when you do get into this or scenario, you also have an increase in your catacholamines on your cortisol, which then further exacerbates the like Wallace's, um, ketone body generations eso. This is one of the new side effects that sort of come about for these drugs on day. Usually, we don't really measure ketose in patients with type two diabetes and sort of scenarios. Where we've done it is maybe if patients, um so they had a period of salvation, but actually they're moving towards saying, Well, if if people are being started on these SGLT two inhibitors, then we need to have a low threshold and diagnosing this And at that point perhaps, um, testing for ketone is my actually be very beneficial. Um, so if you do see, um, patients with sort of you you so that their sugar levels are normal. And that kind of got elevated key tones and picture of acidosis Have a look at the drug chart because it might be precipitated. Um, by one of the few places eso all the drugs we talked about so far have been or all on we move on to what we call injectables. Um, and we touched on sort of being credit in that effect previously. But another drug, which is a ninja action, this gel be one. So the names kind of include exenatide Lyrica tied deluxe tied, um, and they work on a similar basis. But instead of actually on the enzyme that breaks down the GLP ones, we've sort of manage to create a a new dog. So to increase these levels to them further increase the insulin on drug use. The glucagon. Um, just one interesting thing is, actually or ugly coast has a greater ability to potentially this back because of the increase it. And so instead of the eye legally case, um, and this is the summary again, um, these are good, because these cause weight loss. So if you come to sort of the end off the flow chart on your kind of on triple medications, if you've got a patient with a B M I, that's kind of over 35. So beets on, even in patients where you think that perhaps at this point, insulin is not the most notable for them. Perhaps because of compliance or their social situation, then GLP bonds are actually a promising step. Um, they've shown in the trials to produce cardiovascular disease Babel so much improved outcomes with patients who have not unqualified disease. So now the liver disease is kind of gaining traction towards the non alcoholic type, whereas previously most it was down to alcohol. Um, these again have some sort of similar side effects. The DPP four but a bit more of a fakes on July dysfunction on bank tightest. The rare side effects is there's been some reports that it could be linked with thyroid cancer. Um, on the other thing with injectable therapies is the issues with local administration on the injection site reactions. So again, when you're starting on injectables, the education part of ensuring that they actually able to manage it themselves is really important to be able to assess that, Um, some contraindications to sort of end stage renal disease of the Qvar is particularly low on also one complications that patients with diabetes and get is gastro praecis. Um, because of the risk of dysfunction. Um, it's sort of contraindicated in that group of patients. On other things say is that although they are injectables, it's sort of once weekly. So sometimes patients are reassured that it's not sort of every day. Cool. So then we get, uh, kind of the end on drinking about insulin. So if we've gone through all these therapies and we still feel that patients not made good progress, that they're like cement control is still not where we would expect it to be. And they're not meeting the targets that we set. We can look towards insulin therapy for individuals with type two, but often and sort of little suggest this is Patients don't really want to get to the stage because they feel that they've failed in managing their condition. Eso it may actually takes, um, convince convincing start patients on this. You have to then speak from about the regime and make sure that it fits it amongst their day in their work. Life. Eat. Educate them about self monitoring and the importance of this because, as we saw earlier, even if the blood sugars a little bit out of range, it can actually reading have a big impact from the HBA one c levels on by seeming control. Insulins linked with weight gain is well, which might be a factor that we've avoided so far with the or or medications. But, you know, get to the stage and it it may be a side of fact now on injection pain. So depending on the regime, it could be multiple injections per day. And that's quite a big difference if someone was just taking oral tablets. Always time. A nice guidelines of sort of also highlighted this and, um kind of trying to tell us that we really do need to counsel the patients really well. When we're making the change to insulin therapy, I'm not only to be managed, lost the hyperglycemia, monitor it. We also get the side effect of hypoglycemia, so ensuring that patients are well educated on what to do during the hypo on. Also assessing whether they're aware when they're having a hypos. Well, um, now there's various insulin preparations on the guidelines say that the ones for type two diabetes that we sort of start with, um uh, the intermediate incident preparations. But you made them think that that perhaps the control when you review their diaries and things, it's not great around meal times. So then what you can do is add in some short acting insulin to take with the meals or you conduce. You could tweak it so that they have their does just with the largest meal off the day on again. This is gonna be a conversation we had with the patient and how many times a day that comfortable and administering insulin. Um, so we kind of start with the intermediate acting ones. If it's sort of the newly started on insulin on, Do you know if if they want to reduce the number of times the administering it? Sometimes patients living in the community and not able to start in cells they have to have and your sickness something's coming in, then you might go towards the long acting Insulin on local is well, um on, but I found this sort of flow chart because it's always difficult to start on. Insulin don't know exactly how much they'll need. You don't know what you're going to start off with with, actually keep the blood glucose levels on the control. But, um, a typical start is kind of somewhere, um, around 10 units a day or sort of night. No 100.1 not going to units per kilogram per day on then you can kind of tweak this if they then developed hypos. You can reduce the dose, or if it's not really controlling the blood glucose well enough, you can increase by a certain amount of units. And, um, there's no kind of right answer this you don't really You can't really predict how the patient will react to insulin therapy on, but we'll also depend on kind of how much residual be two cell function that they have left. But that's when you start tailoring management specifically for the patient. And then I touched on this earlier. So when your titrate thing, you may think that actually before this meal or after this meal levels are particularly high. So then we can kind of tweak this time, or perhaps that you had it once a day and it's not controlling it. So you may want to sort of split the dose, um, twice a day. So that's sort of a whistle stop tour through medication and diabetes, going through some of the findings in the studies on the trials on your system side of X on benefits. So that's what we have, um, up moment when we're in some clinical practice and these are the kinds of the cases of the kinds of decisions you have to make based on the patient proof all thanks very much. I'm sorry about my technical issues and thank you so much. Um, I'm sure you ever and find it very useful. And I definitely did thank you very much for your attention. And we would like to ask different their feedback from which you can access by scanning the QR code. And if you feel the feedback for me, as I said before, you get a certificate for attendance, which is very good free before you and it's he's crusty. Make sure that the future, um, sessions are improved on down. In the meantime, if you have any questions please put them in a comment section on the Facebook chat and take you to spare a couple of minutes to fill in the feedback form. I was going to wait and see. Um, if there any fatty questions otherwise we just that you fit in the feet like foam, and we'll see next week for it. Um, accession Give you That's a five more minutes and donut questions. We're going to wrap it up. Sorry. Just say that if you want to look more closely at the diagrams I know I rushed through it, but it goes through all the mechanisms quite nicely. And I tried to choose ones that are the most understandable because you can get really confused with all their underlying pathaphysiology. Most people ask me when you get the feedback. Hopefully Oh, you're seeing a QR code. I haven't messed up, so you can access it by the QR code. But what I can do if you're constipated is posted on that shatters. Well, it can try and do that. Yeah, I think we use for toc the feedback. Yeah, Sorry. Just trying to, you know, on how very fine there. Okay, I've got it. one second. You know, I've placed it. All right. I pressed, like Okay, great. So the thank you. The link should be on that too, you know. All right, So there are no questions. Please used Link Teo access to feedback form. It will still be available once we finish their life session. Um, so thank you very much on, but we're going to see everyone next week. Thanks, everyone.