Diabetes Drugs Overview

so today's video is a hugely popular topic it's been requested hundreds of times in the comments section all over my channel we're going to be talking about diabetes drugs now the way that i want you to conceptualize diabetes drugs is to basically break them down into type 1 diabetes drugs and type 2 diabetes drugs and as i make this distinction on this flow chart that you're about to see i'm taking a few liberties here because obviously there is some crossover depending on the severity of type 1 and the severity of type 2 but for the most part you could separate these mentally into insulin being the treatment for type 1 diabetes and the oral agents or the oral anti-hyperglycemia being the treatment for type 2 diabetes and just get comfortable with this distinction because this is really how it's going to appear on usmle and on complex now there are different types of insulins and we'll talk about all of those first and then we'll transition into the major topic of today's video which are all the different oral anti-hyperglycemics just as an overview we'll be talking about things like rapid acting insulin short acting insulin intermediate acting insulin and long-acting insulin and then when we get into again the the main portion of today's video we'll be talking about all the oral agents which include metformin sulfonylureas meglitenides dpp4 inhibitors glp-1 agonists sglt2 inhibitors a carbos thiazo ladino dions and amylon analog so you know that's a mouthful don't get overwhelmed i'm going to break all this down make it really palatable make it super easy i'll give you an awesome mnemonic to help you remember everything that you need to know and you'll leave this video as a master of the pharmacology section as it comes as it pertains to diabetes drugs so let's get started by talking about insulin now basically for the purposes of usmle complex and even your in class medical school exams you're going to have to understand a couple things about insulin the the main part of that is going to be on a graph you're gonna have to know the peak time of the different insulins and how long the different insulins last so while that's somewhat annoying it's also nice to know that there's only three things you need to know about each insulin you need to know the name of the insulin and what category it falls into so you know if for example a spark is that rapid acting short acting intermediate long etc you have to know its peak time and how long it lasts and that's really it so three facts about each insulin not too much to memorize arguably not as bad as learning an oral agent because there's no there's no mechanism here you just have to know again the name of the insulin when it peaks and how long it lasts so let's go through these by category so first we'll talk about the three rapid acting insulins and rapid acting insulins will be depicted on this insulin level versus time graph as shown in red so the rapid acting insulins include lispro aspart and glossine they have a peak time of somewhere around one to one and a half hours and these insulins last for three to four hours okay so if you have a type one diabetic these are usually the insulins that they're taking when they're eating a meal or if their blood if their blood glucose is 200 and they need to correct that and lower it back down to physiologic range this is the type of insulin that accomplishes that it peaks at about one hour it lasts for three to four hours shown in my graph on red the next group of insulins that we'll talk about are the short acting insulins which will be represented by blue there's only one that you need to know so this is pretty sweet for the purposes of memorization and that's regular so literally they named it insulin regular not too hard to remember regular insulin or short acting insulins as a whole last two and have a peak of two and a half hours and lasts for four to six hours so these are longer lasting than the rapid acting hence the name short acting the next group is the intermediate acting and the major player in the intermediate group which is shown on my graph in purple is nph nph insulin has a peak of around 8 hours and overall it lasts for 10 to 16 hours now please take this opportunity to notice that on the axis of my graph the time in hours is not drawn to scale because i'm jumping from 8 to 16 to 24 just to illustrate different insulins but intermediate acting insulin specifically nph has a peak of 8 hours and lasts 10 to 16. the final category shown in green is the long-acting insulins and there are two that you need to know glargine and dedemere there's technically no peak time for the long-acting insulins and these last for 24 hours so these are the insulins that your type 1 diabetics are going to take once a day and this replaces the basal functioning of their pancreas so normally all humans that don't have type 1 diabetes your pancreas is you know outputting a teeny teeny bit of insulin throughout the day just to keep you in that normal physiologic blood glucose range but type 1 diabetics of course don't have that ability because their pancreas has destroyed its own beta cells and therefore there's no insulin production whatsoever so to replace that basal functioning that our pancreases all usually have there's going to be long-acting insulin taken once a day and because it's not peaking and it's just giving you some baseline coverage throughout the day it's acting as the basal rate so the long-acting insulins are really nice in that they don't peak they last for 24 hours they're taken once a day now i know what you're thinking here you're going okay that's not too much information but how am i going to remember which insulin belongs to each category and i've got some pretty sweet mnemonics for you so the first one is that rapid insulins do not lag l-a-g lag for lispro aspart and glolocine rapid-acting insulins do not lag the second mnemonic is regular and short so to remember that regular insulin is in the category of short acting insulin just remember the mnemonic regular and short the third one is that intermediate insulins are not particularly hasty nph not particularly hasty the insulin's name is literally nph so just remember that intermediate is not particularly hasty which of course means that it's not too fast acting and then our final mnemonic is god damn 24 hours is a long time g d for glargine and dedemere so these are four mnemonics literally one short sentence or one short phrase for each of our four categories that will help you remember which insulins belong to which class again before i transition to the type 2 oral agents just remember you only need to know the name of the insulin and which category it belongs to the peak time and the total duration time so when does it peak how long does it last and which of these four categories does it belong to come back to the slide if you want to review the mnemonics but if you just memorize these short phrases you should be good for all of the insulin category so let's just do a check in we've so far covered all of the type 1 diabetes medications namely the different types of insulins now we're going to transition into what will be the bulk of today's video it'll take up most of today's video it'll be the scariest thing for your eyes to look at on the slide but at the end of the day you're going to know all of these oral agents just fine so let's begin our conversation about the type 2 diabetes medications and these are all of the different oral anti-hyperglycemics so we'll start this conversation by talking about the prototypical type 2 diabetes oral agent and that's metformin you might see this written as the biguanide because that's the category of medication but because metformin is really the only biguanide that you need to be familiar with for usmle complex and medical school this we just say metformin we don't say beguanides the mechanism of metformin is that metformin inhibits well it really does a few things it inhibits hepatic gluconeogenesis it increases glycolysis it increases peripheral glucose uptake and the net effect of all three of those actions is that it's decreasing glucose and that is the mechanism by which it treats type 2 diabetes the adverse effects of metformin um and the one that you really need to remember as you if you take anything from this slide is that metformin causes lactic acidosis in renal insufficiency and we'll talk more about that in just a moment the other two adverse effects to know is that metformin can cause a b12 deficiency and it also tends to cause a little bit of gi upset now let's talk briefly about this lactic acidosis which is especially common in renal insufficiency lactic acidosis can be fatal so it's that's why this adverse effect needs to be talked about so you've got your kidneys here and normally metformin is excreted by the kidneys so somebody takes metformin it goes through the system enters the kidneys get filtered out and is excreted through the kidneys now there's a certain situation that you'll encounter a lot once you reach your clinical years of medical school which for most people is still the third year of medical school and that's somebody's you know on the internal medicine service admitted to the hospital and they need to get a ct scan usually not always but a lot of the time in different imaging modalities people are going to be given contrast contrast enhances the image i'm not going to get into radiology right now but it enhances the image and provides more clarity for the physician to look at when the image is done and what happens when you give somebody contrast is that contrast actually can cause a what's called a contrast induced nephropathy so it basically temporarily damages and inhibits the kidneys normal function and what happens in the case of a patient who's taking metformin is that because the kidney is usually excreting metformin if you have a contrast nephropathy and temporarily contrast reduces somebody's renal function then the kidneys cannot excrete metformin and therefore metformin builds up and when metformin builds up because it has a propensity to cause lactic acidosis this can actually cause a fatal toxic lactic acidosis and people die from this so it's very serious this is why when you get into the hospital in your third year of medical school or whenever you're going to be starting up on the floors you'll notice that for a lot of patients that get admitted to the hospital their metformin will be held meaning when they're admitted the um the resident or the attending that's admitting them to the service is not going to continue their metformin and the reason that that's happening is not necessarily because metformin is super toxic it's actually quite safe of a medication it's because the person who's admitting them to the hospital isn't sure if they're going to need contrast and therefore if there would come a time in the next day or two where the patient will need contrast as part of their imaging it's just easier if the metformin is already out of their system so metformin usually gets held when somebody gets admitted to a hospital now how do you remember this this is the biggest point the most high yield thing to know about metformin well metformin starts with met and of course lactic acidosis is a type of metabolic acidosis so you can remember this major adverse reaction in metformin by remembering met because again lactic acidosis is a type of metabolic acidosis and metformin can cause it so that's metformin again know the mechanism but please know this adverse effect of lactic acidosis especially in the setting of renal insufficiency it's very very important and clinically once you start practicing you're going to need to remember this let's talk about our next category of medication so we will transition to the sulfonylureas the sulfonylureas have a mechanism and what they do is they increase the release of insulin the adverse effects of sulfonylureas are hypoglycemia and actually a disulfurium reaction um the mechanism of sophomore areas is that it's increasing the release of insulin by depolarizing the potassium channel so i've i've put a little schematic on the slide so you can see what that looks like but basically the sephonioria drug blocks this channel depolarizes the cell calcium channels are opened and you get the release of insulin that's how sulfonylureas work the sulfonylureas are the drugs that end in ide ide glymepiride glipozide and glyburide and the way that i remembered this back in the day was my mnemonic is thinking about talking to somebody who has type 2 diabetes and what better example than wilford brimley i don't know if you remember the wilford brimley commercials but they always started off with him sitting on a nice couch in a beautiful living room and he in his little southern accent said i'm wilford brimley and i have diabetes and then he would talk you know he'd pitch some diabetes related drug or or device um so what you want to do in this mnemonic is you think about talking to a type 2 diabetic and you tell them i'd take your sulfonylurea if i were you i'd take your sulfonylurea and that reminds me that all of the sulfonylureas have eyed ide they end with ide you tell them i'd take your sulfonylurea so that's it for uria's again the usually the biggest challenge for medical students and other graduate health professionals is grouping the drug into the right category so like if you get a practice question and it says which of the following drugs has the mechanism of blah blah blah and one of the answer choices is glyburide if if you don't know that glyburide is a sulfonylurea even if you know the mechanism of the sophomore ureas you just won't get the question right so these mnemonics are to help you remember what category these drugs belong to so let's do a brief check-in now we've talked about metformin we've talked about sophomoreas we are making progress as we move through the oral anti-hyperglycemics let's keep it rolling by talking about the next category the maglitonides now the meglitenides are almost identical to sulfona ureas they end in ide as you see on the slide and their mechanism is basically the same exact thing but the only caveat that i want to throw in here is that they do it by a different binding site so the sulfonylureas blocked and depolarized a binding site on the potassium channel although the meglitonides have the same cascade of events they they they bind to a certain area they cause depolarization calcium channels are opened and insulin is released they do it at a different binding site than the sulfonylureas but everything else about these drugs is nearly identical so for the purposes again of usmle and comlex i want you to think of mglytenides and sulfonyoreas of doing the same exact thing having both of them end with ide ide and both of them can cause hypoglycemia so like the sulfonylureas my pneumonic from a glittenides is the same thing i'd take your myglytonides so you need to remember i'd take your sulfonylureas and i'd take your mclennaise because these drugs also end in ide as you see at the top of this slide neta glinide and re repaglinide i'm butchering the names i'm sorry um but the big point again they ended an eyed i'd take your mclennaid let's talk about the next category of medications these are the dpp4 inhibitors these are drugs that end in glipton lenoglyptin saxoglyptin cytoglyptin they all end in lipton or glypton the mechanism of dpp4 inhibitors is obviously as the name implies they inhibit dpp-4 which in turn potency potentiates glp-1 and and don't get overwhelmed by these acronyms i'll i'll talk about what this looks like in just a moment the adverse effects of dpp-4 inhibitors are somewhat unique so you definitely need to know them they are urinary infections and respiratory infections um the the biggest thing is to understand what this mechanism is and how it works so let's take a moment to to dive deeper into this so imagine that you eat a juicy hamburger people who aren't in the united states are like god you americans in your filthy diet but let's just imagine that you eat a hamburger what normally happens is when you eat something the body releases glucagon like peptide 1 or glp1 for short and what glucagon like peptide 1 leads to is it promotes insulin release and inhibits glucagon release okay so that's the normal functioning of glp-1 but there is an enzyme in the body known as dipeptityl peptidase 4 or dpp4 for short and what dpp4 does is it inhibits glucagon-like peptide basically knocks it out so if you have this enzyme that's normally present in the body which normally destroys or inhibits glp1 you do not get insulin release you do not get the promotion of insulin release you do not get the inhibition of glucagon release and therefore you can um your your blood glucose can be higher than it otherwise would be because you're not getting the release of insulin and you're not getting the inhibition of glucagon so what a dpp4 inhibitor does perhaps obviously if you look at the name is it inhibits that enzyme so it inhibits dpp4 which means dpp4 is not available to inhibit glp1 which means that there's disinhibition of glp1 which means there's more promotion of insulin release shown in green and more inhibition of glucagon release shown in red and the net effect of that is to lower glucose levels which is how it treats type 2 diabetes so that's how a dpp-4 inhibitor works these are the drugs that end in liptin lenagliptin saxagliptin cetagliptin now while we're talking about this mechanism let's look at the glp1 agonists since the mechanisms are so closely intertwined so the glp1 agonists are exenatide and lyra glutide so these end in tide t-i-d-e the mechanism of the glp-1 agonists as the name suggests and as you just saw on the previous slide is that these potentiate glp-1 or glucagon-like peptide 1. the adverse effects of the glp-1 agonist also a little bit unique so know it it's pancreatitis now let's go back to our slide that we just talked about when we looked at the dpp-4 inhibitors what you can see is that another way to stimulate insulin release and another way to promote the inhibition of glucagon release is to use a glp-1 agonist a glp-1 agonist just potentiates this process and makes it happen faster so the big takeaway from this slide is that dpp-4 inhibitors and glp-1 agonists they both work in a similar fashion in the sense that they're both promoting the same process they just do that differently so how are you going to remember this and more importantly how are you going to remember the different drugs and that they belong to these two individual classes so let's look at glp-1 agonist first you'll notice that they both end in tide and when i think about glp-1 i think about gulp glp gulp like the sound that somebody makes when they're swallowing gulp and i don't know if you guys remember but a few years ago there was this really stupid thing called the tide pod challenge and there were these idiot teenagers eating swallowing tide pods tied for anybody that doesn't know um tide pods are like laundry detergent pods that we put in our washing machines here in the u.s and it cleans our clothes so the way that i remember this is i think about somebody gulping down tide pods these idiots thought this was a good idea and it really wasn't but it went viral viral on social media so um gulping down tide pods is how i remember that the drugs that end in tide belong to the gulp or glp-1 category and here's a clipping from new york times that talked about this when it happened yes people are really eating tide pods it was insane but that's america for you guys now let's talk about dpp for inhibitors you'll notice that all of these drugs end in liptin liptin and that reminded me of a famous brand of iced tea called lipton iced tea and as anybody knows ice tea and tea are diuretics so the way that i remember this is that lipton makes you pee pee four more times and this is awesome because it's lipton tea makes you pp four more times or pp4 for dpp4 inhibitors so you've got all these drugs ending in lipton those are your dpp4 inhibitors and you memorize that with my stupid mnemonic that lipton makes you pee pee four more times you'll never forget this if you write this down and can remember lipton tea or lipton iced tea let's do a little check in and see where we are at this point as far as the type 2 diabetes drugs as far as the oral anti-hyperglycemics we've now thus far talked about metformin sulfonylureas miglitonides and then we just previously on the past few slides grouped in the dpp-4 inhibitors and the glp-1 agonists because they worked it through similar mechanisms let's talk about the sglt2 inhibitors and these are the drugs that end in flozen so can canagliflozin dapagliflozin and empagliflozin the mechanism of the sglt2 inhibitors as the name suggests is that it inhibits a co-transporter called the sodium glucose co-transporter ii and that's what sglt2 stands for and what happens is when you inhibit that co-transporter you're decreasing the reabsorption of glucose in the proximal convoluted tubule of the kidney and we'll talk about that more mec that mechanism more in depth in just a moment the adverse effects of sglt2 inhibitors are very unique and they'll make a lot more sense after we talk about the mechanism but they include glucosuria urinary tract infection and vaginal yeast infections they also can include hyperkalemia and dehydration these these adverse drug effects especially the three on the first line there glucosuria uti and vaginal yeast infection these will make a lot more sense if we dive into the mechanism so let's do that now so i want you to imagine that um we're in the nephron we are in the proximal convoluted tubule and glucose is flowing through so you've had you drank some orange juice your the glucose in your body has been increased and now it's flowing through the nephron normally for glucose to be reabsorbed into the system which in effect makes glucose higher in the body glucose is reabsorbed through a co-transporter and that co-transporter is the sodium glucose cotransporter 2. it's shown here in light blue and as the name suggests it's a co-transporter that operates with both glucose and sodium now normally as i said under normal physiologic conditions the body is detecting glucose flowing through the proximal convoluted tubule it knows exactly how much glucose to reabsorb and it does that to maintain glucose balance but in a type 2 diabetic obviously their blood glucose tends to run a bit high and the goal is to decrease glucose in the body and one of the ways that we do that is by giving somebody this sglt2 inhibitor and by inhibiting the reuptake of glucose through these co-transporters were effectively blocking glucose from being reabsorbed and instead the glucose will flow through and get urinated out now if you think about that the mechanism makes sense about how you decrease glucose but the adverse effect makes even more sense so recall that the adverse effect was glucose urea so more glucose in your urine which causes both urinary tract infections and vaginal yeast infections and that should make perfect sense to you guys if there's more glucose in the urine it's more of a nidus for some type of pathogen to use it to utilize that glucose as fuel to infect the urine and for yeast to grow um on the vagina or in the vagina so again the adverse effects glucosuria uti and vaginal yeast infection should make perfect sense considering the mechanism basically leads to more glucose in the urine now how do you remember that the the flows in drugs are the sglt2 inhibitors well this is really easy just remember flows in through the urine or flowing through the urine and that will remind you that the drugs that end in flows in or flow in all go through the urine and are sglt2 inhibitors now let's talk about alpha glucosidase inhibitors and the major drug here that you need to know is a carbos but the secondary one that sometimes shows up is also miglitol the mechanism of the alpha glucosidase inhibitors is that these inhibit intestinal brush border alpha glucosidases and you might remember that the alpha glucosidase enzyme is present in the intestinal brush border back from the gi section the adverse effect here again this will make more sense after we dive into the mechanism but it's gi upset gas and bloating so let's just take a visit to the intestine you've got these oligosaccharides which are basically the precursor components of glucose that have not yet been broken down into their monosaccharide derivatives basically glucose is a monosaccharide and it comes from oligosaccharides so as these oligosaccharides flow through the intestine they pass the brush border which has this enzyme alpha glucosidase just chillin on the side and that alpha glucosidase catalyzes the conversion of the oligosaccharide to its monosaccharide glucose derivative and then once that monosaccharide glucose derivative has been made which again that that whole conversion is done by alpha glucosidase that glucose can be absorbed through the intestinal wall and lead to you know higher glucose levels in the body now normally as i said with other drugs as examples the body knows exactly how much glucose it needs to absorb to keep a perfect balance but in type 2 diabetes that balance is just not working and one of the ways to decrease glucose is to prevent this absorption of glucose through the intestinal wall and one of the ways we do that is by giving alka-glucosidase inhibitors so if you inhibit the enzyme that converts the oligosaccharide into its monosaccharide glucose derivative you never have the availability of the monosaccharide glucose to be reabsorbed so you basically knock out this process you've got a liga oligosaccharides just sitting in the intestines and they'll proceed through the intestines and get excreted in the feces and if you think about this the adverse effects should make perfect sense because you if you have more oligosaccharide in the intestine it's going to cause a little bit of gi upset it's going to cause a little bit of gas a little bit of bloating now i know what you're thinking how do i remember that a carbos is an alpha glucosidase inhibitor and that's pretty easy because a carb literally means without carbs so you're never getting the glucose because you're never converting it and therefore the intestine is without carbs so that's how i remember alpha glucosidase inhibitors again the big one is a carbos so here is where we are so far you guys are making awesome progress if you're following me we've talked about metformin we've talked about sulfonylureas we've talked about the glytenides we've talked about both the dpp4 inhibitors and the glp-1 agonists we've talked about sglt2 inhibitors and how they're very unique in the kidney and now we've talked about a carbos and how it's very unique in the intestine let's wrap up by talking about the final two categories of the type 2 diabetes drugs the next one is the thiazo ladinodions and that's the hardest one to say by far these are your drugs that end in glitzone so pioglitazone and rosyglitazone the mechanism of the tzds as i will call them because i do not want to pronounce that drug name again is that these bind to the peroxisome proliferator activated receptor gamma or ppar gamma binding site which is just a nuclear factor and the net effect of that nuclear factor is to increase insulin sensitivity the adverse effects of the tcds are somewhat unique heart failure and increased risk of fracture so definitely know the adverse effects of all these drugs because they're all pretty unique um how do you remember this this is a tough one because the name is so weird but if you look at the drugs you'll notice that they all have glitter or glitter if you like to party in the name and that reminds me of um glitter you know like throwing glitter up in the air or confetti some type of party material and my mnemonic here is that you wanna you wanna bring glitter to the party glitter for glittazone and party for ppar helps me memorize the mechanism ppar gamma so bring glitta to the party that's it for tzd's nothing else to know know the two adverse effects know the mechanism because the mechanism is very unique finally we made it guys let's wrap up by talking about the amalen analogs and luckily there's not a lot to know about the amalen analogues if if on usmle and comlex i would argue to you that these will show up the least of any possible type 2 diabetes drug so you know if you've made it to this point in the video and you're like i have no brain space left then i would punt these because this drug um they're really the only one you need to know is pram lineatide it's not hugely high yield but i'll include it here the mechanism is that it's a synthetic amylin that works alongside insulin so i'm not going to get into the the subtlety and the the physiology of how amylin works but it works with insulin to help insulin do its job and this is just a synthetic amyloid so you're basically giving something that is a synthetic chemical that usually will help insulin promote the decrease of glucose adverse effect is hypoglycemia nothing really major or high yield to know here i don't have a mnemonic for you just know that amylin works like insulin and that should make sense because they both end in lin insulin amylin and that's it guys so we've gone through this video we talked about type 1 diabetes insulins and type 2 diabetes anti-oral hyper anti-hyperglycemics as you can tell my mouth is tired we talked a lot for your studying pleasure here is a summary chart of all of my mnemonics for the type 2 drugs because those tend to be the hardest ones for students to memorize you can go through this i'm not going to read it to you but again what i will leave you with and what you should take away from this video is the different classes of the drugs for the type 2 drugs which drugs belong to which class because you're going to need to make that association if you want to get the questions right the mechanisms the adverse effects and that's pretty much it for the for the type two drugs and then just to revisit the first topic we talked about for those insulins just remember peak time duration time and which insulin belongs to which category this was a long video uh thank you for sticking with me go through it a few times and you'll be a pro at these different drugs diabetes drugs are everywhere right everybody is diabetic these days so you're going to need to know these they're high yield for tests they're higher for real life know them well okay good luck everybody

so today&#39;s video is a hugely popular topic it&#39;s been requested hundreds of times in the comments section all over my channel we&#39;re going to be talking about diabetes drugs now the way that i want you to conceptualize diabetes drugs is to basically break them down into type 1 diabetes drugs and type 2 diabetes drugs and as i make this distinction on this flow chart that you&#39;re about to see i&#39;m taking a few liberties here because obviously there is some crossover depending on the severity of type 1 and the severity of type 2 but for the most part you could separate these mentally into insulin being the treatment for type 1 diabetes and the oral agents or the oral anti-hyperglycemia being the treatment for type 2 diabetes and just get comfortable with this distinction because this is really how it&#39;s going to appear on usmle and on complex now there are different types of insulins and we&#39;ll talk about all of those first and then we&#39;ll transition into the major topic of today&#39;s video which are all the different oral anti-hyperglycemics just as an overview we&#39;ll be talking about things like rapid acting insulin short acting insulin intermediate acting insulin and long-acting insulin and then when we get into again the the main portion of today&#39;s video we&#39;ll be talking about all the oral agents which include metformin sulfonylureas meglitenides dpp4 inhibitors glp-1 agonists sglt2 inhibitors a carbos thiazo ladino dions and amylon analog so you know that&#39;s a mouthful don&#39;t get overwhelmed i&#39;m going to break all this down make it really palatable make it super easy i&#39;ll give you an awesome mnemonic to help you remember everything that you need to know and you&#39;ll leave this video as a master of the pharmacology section as it comes as it pertains to diabetes drugs so let&#39;s get started by talking about insulin now basically for the purposes of usmle complex and even your in class medical school exams you&#39;re going to have to understand a couple things about insulin the the main part of that is going to be on a graph you&#39;re gonna have to know the peak time of the different insulins and how long the different insulins last so while that&#39;s somewhat annoying it&#39;s also nice to know that there&#39;s only three things you need to know about each insulin you need to know the name of the insulin and what category it falls into so you know if for example a spark is that rapid acting short acting intermediate long etc you have to know its peak time and how long it lasts and that&#39;s really it so three facts about each insulin not too much to memorize arguably not as bad as learning an oral agent because there&#39;s no there&#39;s no mechanism here you just have to know again the name of the insulin when it peaks and how long it lasts so let&#39;s go through these by category so first we&#39;ll talk about the three rapid acting insulins and rapid acting insulins will be depicted on this insulin level versus time graph as shown in red so the rapid acting insulins include lispro aspart and glossine they have a peak time of somewhere around one to one and a half hours and these insulins last for three to four hours okay so if you have a type one diabetic these are usually the insulins that they&#39;re taking when they&#39;re eating a meal or if their blood if their blood glucose is 200 and they need to correct that and lower it back down to physiologic range this is the type of insulin that accomplishes that it peaks at about one hour it lasts for three to four hours shown in my graph on red the next group of insulins that we&#39;ll talk about are the short acting insulins which will be represented by blue there&#39;s only one that you need to know so this is pretty sweet for the purposes of memorization and that&#39;s regular so literally they named it insulin regular not too hard to remember regular insulin or short acting insulins as a whole last two and have a peak of two and a half hours and lasts for four to six hours so these are longer lasting than the rapid acting hence the name short acting the next group is the intermediate acting and the major player in the intermediate group which is shown on my graph in purple is nph nph insulin has a peak of around 8 hours and overall it lasts for 10 to 16 hours now please take this opportunity to notice that on the axis of my graph the time in hours is not drawn to scale because i&#39;m jumping from 8 to 16 to 24 just to illustrate different insulins but intermediate acting insulin specifically nph has a peak of 8 hours and lasts 10 to 16. the final category shown in green is the long-acting insulins and there are two that you need to know glargine and dedemere there&#39;s technically no peak time for the long-acting insulins and these last for 24 hours so these are the insulins that your type 1 diabetics are going to take once a day and this replaces the basal functioning of their pancreas so normally all humans that don&#39;t have type 1 diabetes your pancreas is you know outputting a teeny teeny bit of insulin throughout the day just to keep you in that normal physiologic blood glucose range but type 1 diabetics of course don&#39;t have that ability because their pancreas has destroyed its own beta cells and therefore there&#39;s no insulin production whatsoever so to replace that basal functioning that our pancreases all usually have there&#39;s going to be long-acting insulin taken once a day and because it&#39;s not peaking and it&#39;s just giving you some baseline coverage throughout the day it&#39;s acting as the basal rate so the long-acting insulins are really nice in that they don&#39;t peak they last for 24 hours they&#39;re taken once a day now i know what you&#39;re thinking here you&#39;re going okay that&#39;s not too much information but how am i going to remember which insulin belongs to each category and i&#39;ve got some pretty sweet mnemonics for you so the first one is that rapid insulins do not lag l-a-g lag for lispro aspart and glolocine rapid-acting insulins do not lag the second mnemonic is regular and short so to remember that regular insulin is in the category of short acting insulin just remember the mnemonic regular and short the third one is that intermediate insulins are not particularly hasty nph not particularly hasty the insulin&#39;s name is literally nph so just remember that intermediate is not particularly hasty which of course means that it&#39;s not too fast acting and then our final mnemonic is god damn 24 hours is a long time g d for glargine and dedemere so these are four mnemonics literally one short sentence or one short phrase for each of our four categories that will help you remember which insulins belong to which class again before i transition to the type 2 oral agents just remember you only need to know the name of the insulin and which category it belongs to the peak time and the total duration time so when does it peak how long does it last and which of these four categories does it belong to come back to the slide if you want to review the mnemonics but if you just memorize these short phrases you should be good for all of the insulin category so let&#39;s just do a check in we&#39;ve so far covered all of the type 1 diabetes medications namely the different types of insulins now we&#39;re going to transition into what will be the bulk of today&#39;s video it&#39;ll take up most of today&#39;s video it&#39;ll be the scariest thing for your eyes to look at on the slide but at the end of the day you&#39;re going to know all of these oral agents just fine so let&#39;s begin our conversation about the type 2 diabetes medications and these are all of the different oral anti-hyperglycemics so we&#39;ll start this conversation by talking about the prototypical type 2 diabetes oral agent and that&#39;s metformin you might see this written as the biguanide because that&#39;s the category of medication but because metformin is really the only biguanide that you need to be familiar with for usmle complex and medical school this we just say metformin we don&#39;t say beguanides the mechanism of metformin is that metformin inhibits well it really does a few things it inhibits hepatic gluconeogenesis it increases glycolysis it increases peripheral glucose uptake and the net effect of all three of those actions is that it&#39;s decreasing glucose and that is the mechanism by which it treats type 2 diabetes the adverse effects of metformin um and the one that you really need to remember as you if you take anything from this slide is that metformin causes lactic acidosis in renal insufficiency and we&#39;ll talk more about that in just a moment the other two adverse effects to know is that metformin can cause a b12 deficiency and it also tends to cause a little bit of gi upset now let&#39;s talk briefly about this lactic acidosis which is especially common in renal insufficiency lactic acidosis can be fatal so it&#39;s that&#39;s why this adverse effect needs to be talked about so you&#39;ve got your kidneys here and normally metformin is excreted by the kidneys so somebody takes metformin it goes through the system enters the kidneys get filtered out and is excreted through the kidneys now there&#39;s a certain situation that you&#39;ll encounter a lot once you reach your clinical years of medical school which for most people is still the third year of medical school and that&#39;s somebody&#39;s you know on the internal medicine service admitted to the hospital and they need to get a ct scan usually not always but a lot of the time in different imaging modalities people are going to be given contrast contrast enhances the image i&#39;m not going to get into radiology right now but it enhances the image and provides more clarity for the physician to look at when the image is done and what happens when you give somebody contrast is that contrast actually can cause a what&#39;s called a contrast induced nephropathy so it basically temporarily damages and inhibits the kidneys normal function and what happens in the case of a patient who&#39;s taking metformin is that because the kidney is usually excreting metformin if you have a contrast nephropathy and temporarily contrast reduces somebody&#39;s renal function then the kidneys cannot excrete metformin and therefore metformin builds up and when metformin builds up because it has a propensity to cause lactic acidosis this can actually cause a fatal toxic lactic acidosis and people die from this so it&#39;s very serious this is why when you get into the hospital in your third year of medical school or whenever you&#39;re going to be starting up on the floors you&#39;ll notice that for a lot of patients that get admitted to the hospital their metformin will be held meaning when they&#39;re admitted the um the resident or the attending that&#39;s admitting them to the service is not going to continue their metformin and the reason that that&#39;s happening is not necessarily because metformin is super toxic it&#39;s actually quite safe of a medication it&#39;s because the person who&#39;s admitting them to the hospital isn&#39;t sure if they&#39;re going to need contrast and therefore if there would come a time in the next day or two where the patient will need contrast as part of their imaging it&#39;s just easier if the metformin is already out of their system so metformin usually gets held when somebody gets admitted to a hospital now how do you remember this this is the biggest point the most high yield thing to know about metformin well metformin starts with met and of course lactic acidosis is a type of metabolic acidosis so you can remember this major adverse reaction in metformin by remembering met because again lactic acidosis is a type of metabolic acidosis and metformin can cause it so that&#39;s metformin again know the mechanism but please know this adverse effect of lactic acidosis especially in the setting of renal insufficiency it&#39;s very very important and clinically once you start practicing you&#39;re going to need to remember this let&#39;s talk about our next category of medication so we will transition to the sulfonylureas the sulfonylureas have a mechanism and what they do is they increase the release of insulin the adverse effects of sulfonylureas are hypoglycemia and actually a disulfurium reaction um the mechanism of sophomore areas is that it&#39;s increasing the release of insulin by depolarizing the potassium channel so i&#39;ve i&#39;ve put a little schematic on the slide so you can see what that looks like but basically the sephonioria drug blocks this channel depolarizes the cell calcium channels are opened and you get the release of insulin that&#39;s how sulfonylureas work the sulfonylureas are the drugs that end in ide ide glymepiride glipozide and glyburide and the way that i remembered this back in the day was my mnemonic is thinking about talking to somebody who has type 2 diabetes and what better example than wilford brimley i don&#39;t know if you remember the wilford brimley commercials but they always started off with him sitting on a nice couch in a beautiful living room and he in his little southern accent said i&#39;m wilford brimley and i have diabetes and then he would talk you know he&#39;d pitch some diabetes related drug or or device um so what you want to do in this mnemonic is you think about talking to a type 2 diabetic and you tell them i&#39;d take your sulfonylurea if i were you i&#39;d take your sulfonylurea and that reminds me that all of the sulfonylureas have eyed ide they end with ide you tell them i&#39;d take your sulfonylurea so that&#39;s it for uria&#39;s again the usually the biggest challenge for medical students and other graduate health professionals is grouping the drug into the right category so like if you get a practice question and it says which of the following drugs has the mechanism of blah blah blah and one of the answer choices is glyburide if if you don&#39;t know that glyburide is a sulfonylurea even if you know the mechanism of the sophomore ureas you just won&#39;t get the question right so these mnemonics are to help you remember what category these drugs belong to so let&#39;s do a brief check-in now we&#39;ve talked about metformin we&#39;ve talked about sophomoreas we are making progress as we move through the oral anti-hyperglycemics let&#39;s keep it rolling by talking about the next category the maglitonides now the meglitenides are almost identical to sulfona ureas they end in ide as you see on the slide and their mechanism is basically the same exact thing but the only caveat that i want to throw in here is that they do it by a different binding site so the sulfonylureas blocked and depolarized a binding site on the potassium channel although the meglitonides have the same cascade of events they they they bind to a certain area they cause depolarization calcium channels are opened and insulin is released they do it at a different binding site than the sulfonylureas but everything else about these drugs is nearly identical so for the purposes again of usmle and comlex i want you to think of mglytenides and sulfonyoreas of doing the same exact thing having both of them end with ide ide and both of them can cause hypoglycemia so like the sulfonylureas my pneumonic from a glittenides is the same thing i&#39;d take your myglytonides so you need to remember i&#39;d take your sulfonylureas and i&#39;d take your mclennaise because these drugs also end in ide as you see at the top of this slide neta glinide and re repaglinide i&#39;m butchering the names i&#39;m sorry um but the big point again they ended an eyed i&#39;d take your mclennaid let&#39;s talk about the next category of medications these are the dpp4 inhibitors these are drugs that end in glipton lenoglyptin saxoglyptin cytoglyptin they all end in lipton or glypton the mechanism of dpp4 inhibitors is obviously as the name implies they inhibit dpp-4 which in turn potency potentiates glp-1 and and don&#39;t get overwhelmed by these acronyms i&#39;ll i&#39;ll talk about what this looks like in just a moment the adverse effects of dpp-4 inhibitors are somewhat unique so you definitely need to know them they are urinary infections and respiratory infections um the the biggest thing is to understand what this mechanism is and how it works so let&#39;s take a moment to to dive deeper into this so imagine that you eat a juicy hamburger people who aren&#39;t in the united states are like god you americans in your filthy diet but let&#39;s just imagine that you eat a hamburger what normally happens is when you eat something the body releases glucagon like peptide 1 or glp1 for short and what glucagon like peptide 1 leads to is it promotes insulin release and inhibits glucagon release okay so that&#39;s the normal functioning of glp-1 but there is an enzyme in the body known as dipeptityl peptidase 4 or dpp4 for short and what dpp4 does is it inhibits glucagon-like peptide basically knocks it out so if you have this enzyme that&#39;s normally present in the body which normally destroys or inhibits glp1 you do not get insulin release you do not get the promotion of insulin release you do not get the inhibition of glucagon release and therefore you can um your your blood glucose can be higher than it otherwise would be because you&#39;re not getting the release of insulin and you&#39;re not getting the inhibition of glucagon so what a dpp4 inhibitor does perhaps obviously if you look at the name is it inhibits that enzyme so it inhibits dpp4 which means dpp4 is not available to inhibit glp1 which means that there&#39;s disinhibition of glp1 which means there&#39;s more promotion of insulin release shown in green and more inhibition of glucagon release shown in red and the net effect of that is to lower glucose levels which is how it treats type 2 diabetes so that&#39;s how a dpp-4 inhibitor works these are the drugs that end in liptin lenagliptin saxagliptin cetagliptin now while we&#39;re talking about this mechanism let&#39;s look at the glp1 agonists since the mechanisms are so closely intertwined so the glp1 agonists are exenatide and lyra glutide so these end in tide t-i-d-e the mechanism of the glp-1 agonists as the name suggests and as you just saw on the previous slide is that these potentiate glp-1 or glucagon-like peptide 1. the adverse effects of the glp-1 agonist also a little bit unique so know it it&#39;s pancreatitis now let&#39;s go back to our slide that we just talked about when we looked at the dpp-4 inhibitors what you can see is that another way to stimulate insulin release and another way to promote the inhibition of glucagon release is to use a glp-1 agonist a glp-1 agonist just potentiates this process and makes it happen faster so the big takeaway from this slide is that dpp-4 inhibitors and glp-1 agonists they both work in a similar fashion in the sense that they&#39;re both promoting the same process they just do that differently so how are you going to remember this and more importantly how are you going to remember the different drugs and that they belong to these two individual classes so let&#39;s look at glp-1 agonist first you&#39;ll notice that they both end in tide and when i think about glp-1 i think about gulp glp gulp like the sound that somebody makes when they&#39;re swallowing gulp and i don&#39;t know if you guys remember but a few years ago there was this really stupid thing called the tide pod challenge and there were these idiot teenagers eating swallowing tide pods tied for anybody that doesn&#39;t know um tide pods are like laundry detergent pods that we put in our washing machines here in the u.s and it cleans our clothes so the way that i remember this is i think about somebody gulping down tide pods these idiots thought this was a good idea and it really wasn&#39;t but it went viral viral on social media so um gulping down tide pods is how i remember that the drugs that end in tide belong to the gulp or glp-1 category and here&#39;s a clipping from new york times that talked about this when it happened yes people are really eating tide pods it was insane but that&#39;s america for you guys now let&#39;s talk about dpp for inhibitors you&#39;ll notice that all of these drugs end in liptin liptin and that reminded me of a famous brand of iced tea called lipton iced tea and as anybody knows ice tea and tea are diuretics so the way that i remember this is that lipton makes you pee pee four more times and this is awesome because it&#39;s lipton tea makes you pp four more times or pp4 for dpp4 inhibitors so you&#39;ve got all these drugs ending in lipton those are your dpp4 inhibitors and you memorize that with my stupid mnemonic that lipton makes you pee pee four more times you&#39;ll never forget this if you write this down and can remember lipton tea or lipton iced tea let&#39;s do a little check in and see where we are at this point as far as the type 2 diabetes drugs as far as the oral anti-hyperglycemics we&#39;ve now thus far talked about metformin sulfonylureas miglitonides and then we just previously on the past few slides grouped in the dpp-4 inhibitors and the glp-1 agonists because they worked it through similar mechanisms let&#39;s talk about the sglt2 inhibitors and these are the drugs that end in flozen so can canagliflozin dapagliflozin and empagliflozin the mechanism of the sglt2 inhibitors as the name suggests is that it inhibits a co-transporter called the sodium glucose co-transporter ii and that&#39;s what sglt2 stands for and what happens is when you inhibit that co-transporter you&#39;re decreasing the reabsorption of glucose in the proximal convoluted tubule of the kidney and we&#39;ll talk about that more mec that mechanism more in depth in just a moment the adverse effects of sglt2 inhibitors are very unique and they&#39;ll make a lot more sense after we talk about the mechanism but they include glucosuria urinary tract infection and vaginal yeast infections they also can include hyperkalemia and dehydration these these adverse drug effects especially the three on the first line there glucosuria uti and vaginal yeast infection these will make a lot more sense if we dive into the mechanism so let&#39;s do that now so i want you to imagine that um we&#39;re in the nephron we are in the proximal convoluted tubule and glucose is flowing through so you&#39;ve had you drank some orange juice your the glucose in your body has been increased and now it&#39;s flowing through the nephron normally for glucose to be reabsorbed into the system which in effect makes glucose higher in the body glucose is reabsorbed through a co-transporter and that co-transporter is the sodium glucose cotransporter 2. it&#39;s shown here in light blue and as the name suggests it&#39;s a co-transporter that operates with both glucose and sodium now normally as i said under normal physiologic conditions the body is detecting glucose flowing through the proximal convoluted tubule it knows exactly how much glucose to reabsorb and it does that to maintain glucose balance but in a type 2 diabetic obviously their blood glucose tends to run a bit high and the goal is to decrease glucose in the body and one of the ways that we do that is by giving somebody this sglt2 inhibitor and by inhibiting the reuptake of glucose through these co-transporters were effectively blocking glucose from being reabsorbed and instead the glucose will flow through and get urinated out now if you think about that the mechanism makes sense about how you decrease glucose but the adverse effect makes even more sense so recall that the adverse effect was glucose urea so more glucose in your urine which causes both urinary tract infections and vaginal yeast infections and that should make perfect sense to you guys if there&#39;s more glucose in the urine it&#39;s more of a nidus for some type of pathogen to use it to utilize that glucose as fuel to infect the urine and for yeast to grow um on the vagina or in the vagina so again the adverse effects glucosuria uti and vaginal yeast infection should make perfect sense considering the mechanism basically leads to more glucose in the urine now how do you remember that the the flows in drugs are the sglt2 inhibitors well this is really easy just remember flows in through the urine or flowing through the urine and that will remind you that the drugs that end in flows in or flow in all go through the urine and are sglt2 inhibitors now let&#39;s talk about alpha glucosidase inhibitors and the major drug here that you need to know is a carbos but the secondary one that sometimes shows up is also miglitol the mechanism of the alpha glucosidase inhibitors is that these inhibit intestinal brush border alpha glucosidases and you might remember that the alpha glucosidase enzyme is present in the intestinal brush border back from the gi section the adverse effect here again this will make more sense after we dive into the mechanism but it&#39;s gi upset gas and bloating so let&#39;s just take a visit to the intestine you&#39;ve got these oligosaccharides which are basically the precursor components of glucose that have not yet been broken down into their monosaccharide derivatives basically glucose is a monosaccharide and it comes from oligosaccharides so as these oligosaccharides flow through the intestine they pass the brush border which has this enzyme alpha glucosidase just chillin on the side and that alpha glucosidase catalyzes the conversion of the oligosaccharide to its monosaccharide glucose derivative and then once that monosaccharide glucose derivative has been made which again that that whole conversion is done by alpha glucosidase that glucose can be absorbed through the intestinal wall and lead to you know higher glucose levels in the body now normally as i said with other drugs as examples the body knows exactly how much glucose it needs to absorb to keep a perfect balance but in type 2 diabetes that balance is just not working and one of the ways to decrease glucose is to prevent this absorption of glucose through the intestinal wall and one of the ways we do that is by giving alka-glucosidase inhibitors so if you inhibit the enzyme that converts the oligosaccharide into its monosaccharide glucose derivative you never have the availability of the monosaccharide glucose to be reabsorbed so you basically knock out this process you&#39;ve got a liga oligosaccharides just sitting in the intestines and they&#39;ll proceed through the intestines and get excreted in the feces and if you think about this the adverse effects should make perfect sense because you if you have more oligosaccharide in the intestine it&#39;s going to cause a little bit of gi upset it&#39;s going to cause a little bit of gas a little bit of bloating now i know what you&#39;re thinking how do i remember that a carbos is an alpha glucosidase inhibitor and that&#39;s pretty easy because a carb literally means without carbs so you&#39;re never getting the glucose because you&#39;re never converting it and therefore the intestine is without carbs so that&#39;s how i remember alpha glucosidase inhibitors again the big one is a carbos so here is where we are so far you guys are making awesome progress if you&#39;re following me we&#39;ve talked about metformin we&#39;ve talked about sulfonylureas we&#39;ve talked about the glytenides we&#39;ve talked about both the dpp4 inhibitors and the glp-1 agonists we&#39;ve talked about sglt2 inhibitors and how they&#39;re very unique in the kidney and now we&#39;ve talked about a carbos and how it&#39;s very unique in the intestine let&#39;s wrap up by talking about the final two categories of the type 2 diabetes drugs the next one is the thiazo ladinodions and that&#39;s the hardest one to say by far these are your drugs that end in glitzone so pioglitazone and rosyglitazone the mechanism of the tzds as i will call them because i do not want to pronounce that drug name again is that these bind to the peroxisome proliferator activated receptor gamma or ppar gamma binding site which is just a nuclear factor and the net effect of that nuclear factor is to increase insulin sensitivity the adverse effects of the tcds are somewhat unique heart failure and increased risk of fracture so definitely know the adverse effects of all these drugs because they&#39;re all pretty unique um how do you remember this this is a tough one because the name is so weird but if you look at the drugs you&#39;ll notice that they all have glitter or glitter if you like to party in the name and that reminds me of um glitter you know like throwing glitter up in the air or confetti some type of party material and my mnemonic here is that you wanna you wanna bring glitter to the party glitter for glittazone and party for ppar helps me memorize the mechanism ppar gamma so bring glitta to the party that&#39;s it for tzd&#39;s nothing else to know know the two adverse effects know the mechanism because the mechanism is very unique finally we made it guys let&#39;s wrap up by talking about the amalen analogs and luckily there&#39;s not a lot to know about the amalen analogues if if on usmle and comlex i would argue to you that these will show up the least of any possible type 2 diabetes drug so you know if you&#39;ve made it to this point in the video and you&#39;re like i have no brain space left then i would punt these because this drug um they&#39;re really the only one you need to know is pram lineatide it&#39;s not hugely high yield but i&#39;ll include it here the mechanism is that it&#39;s a synthetic amylin that works alongside insulin so i&#39;m not going to get into the the subtlety and the the physiology of how amylin works but it works with insulin to help insulin do its job and this is just a synthetic amyloid so you&#39;re basically giving something that is a synthetic chemical that usually will help insulin promote the decrease of glucose adverse effect is hypoglycemia nothing really major or high yield to know here i don&#39;t have a mnemonic for you just know that amylin works like insulin and that should make sense because they both end in lin insulin amylin and that&#39;s it guys so we&#39;ve gone through this video we talked about type 1 diabetes insulins and type 2 diabetes anti-oral hyper anti-hyperglycemics as you can tell my mouth is tired we talked a lot for your studying pleasure here is a summary chart of all of my mnemonics for the type 2 drugs because those tend to be the hardest ones for students to memorize you can go through this i&#39;m not going to read it to you but again what i will leave you with and what you should take away from this video is the different classes of the drugs for the type 2 drugs which drugs belong to which class because you&#39;re going to need to make that association if you want to get the questions right the mechanisms the adverse effects and that&#39;s pretty much it for the for the type two drugs and then just to revisit the first topic we talked about for those insulins just remember peak time duration time and which insulin belongs to which category this was a long video uh thank you for sticking with me go through it a few times and you&#39;ll be a pro at these different drugs diabetes drugs are everywhere right everybody is diabetic these days so you&#39;re going to need to know these they&#39;re high yield for tests they&#39;re higher for real life know them well okay good luck everybody

Transcript for:Diabetes Drugs Overview

Transcript for:
Diabetes Drugs Overview