Insulin Therapy: Pharmacologic Strategies and Patient-Centered Approaches *ACPE-Accredited*

(upbeat music) - What is going on everybody? Welcome back to another episode of your favorite podcast, the core console, Darax, evidence based medicine podcast. Cole, how's everything going on your end, my man? - Doing good, maybe your favorite podcasts. - There's better podcasts out there. So it might not be your favorite, but maybe your favorite pharmacy podcast. - I would say, I mean, there's so many more better podcasts, it's not even funny, but you know, just trying to, sound real confident there at the beginning. (laughing) - Yeah, that's good. - That's a good way to start. - Yeah, it actually cracks me up though. I have some friends and some of the people I work with that will listen to my podcast sometimes like on the way home from where I get on my, I can't imagine a worst thing that I feel as news to my voice, like I'm the man for like a busy day or it could sound horrendous. - Yeah, we thought, we're very thankful to those of you who will do enjoy it. - We thought everybody had a podcast seven and a half years ago when we started this one. Like we were not first to the party by any means, but now everybody has a podcast every single person. - Yeah, I haven't even looked in a while at a bed, it's insane how many pharmacy podcasts they're out like Mount Spotify. - They're not just pharmacy, I haven't looked at pharmacy. I'm talking about in general, just any of them. - Don't lie, you listen to all the pharmacy podcasts, don't you? - Yeah, that's what I do in my free time. (laughing) - It's more than this. - Yep, yep, have a subscriber, I know how it goes. - Yeah. - So that's neither here nor there, because it's a night we're gonna be to cover another one of our diabetes topics, which is colonized, probably agreed upon favorite type of topic to go through. Or subject matter, I should say. But this is gonna be another recorded episode. But tonight's going to focus primarily on insulin therapy. And so we did a, what is that panel discussion with FreeCE, what, two, three months ago, something like that? - Yeah, it wasn't April, early April. - Okay, so we had to kind of keep all of the pharmacotherapy for type two diabetes, plus some updates and things, kind of narrow down to an hour. So we didn't get to spend much time at all talking about insulin therapy. So kind of we're discussing topics and things that we haven't really done for accreditation purposes yet. And insulin therapy seemed like it'd be a good one to kind of put into one episode by itself. So we can really dive into it a little bit more. - Agreed, and insulin is still relevant, even with all the GLP ones out there. There's many instances where insulin is used. So, yeah, maybe not the same type two as it used to be, but it's still certainly used. - Yeah, and so hopefully this is the top of the y'all a little like, but for those of you who are FreeCE members, make sure that you listen for the password that will give you somewhere in this episode. And that password will give you access to the post-activity test that you can take on FreeCE's website. You pass the 10 question multiple choice tests and you get one hour of continuing education credit for pharmacists and nurses. And as always, definitely, if you're not a member of FreeCE, go check them out. They have lots of great content, monologues. They have a different live events, panel discussions, all kinds of great stuff. So check them out. And we appreciate them to continue partnering with us and having us be part of their external team, if you will. All right, to kick things off, I guess, like Cole mentioned, obviously type one diabetes, insulin is a prominent role as far as the therapy type two. There have been some other medications that have come along that have replaced the need in some cases for insulin, but insulin definitely is still a very big part of type two management, especially if it's more advanced or uncontrolled disease. And then gestational diabetes, definitely a very important aspect of that management as well, assuming that the patient agrees to it. But just to review some basic definitions since all three of these involve insulin therapy to some extent, obviously when we talk about type one diabetes, we're talking about the actual autoimmune destruction of the beta cells. So pancreas is no longer able to produce insulin or at least anywhere near the sufficient amounts of insulin to regulate blood glucose on a appropriate way. Historically, when we've kind of thought about someone with type one, we would think of patients that had been diagnosed as adolescents. And some of them really, really young children. And while younger patients who do get diagnosed with type one, do have a more rapid rate of beta cell destruction and will present with a ketoacidosis and all that, there are patients who will have a more insidious route to their beta cell destruction. And they may have such a slow onset, but they maintain sufficient insulin secretion to prevent them from going into a ketoacidosis for years. The technical term in this situation is autoimmune diabetes and adults, but essentially is still type one. It's treated like a type one. And in my own practice, I found that difficult. When you have a patient who just doesn't, one doesn't fit the phenotypic look of a type two. It doesn't have a lot of the typical features we would see in, we're trying multiple medications. Everything seems to be on the right track, but their blood sugar's not responding. Those are some patients that maybe we need to look and see if they are a potential late onset type one. But these patients are going to be insulin dependent, whether they are diagnosed at any age. Eventually we'll get to a point where they are insulin dependent. And so very strict insulin control is going to be ideal for managing these patients. And so we'll talk about some ways to kind of pinpoint the patient's insulin dosing and things towards the end for our type ones. Our type two is our insulin resistant. And so these patients, their insulin is just not responding appropriately to glucose levels, and so the insulin is being produced. It's just the body's response, so they're resistance to insulin. We can overcome that with various medications, but also giving exogenous insulin. And we'll kind of talk about how we add insulin therapy and the order in which we do it when we talk about the type two management. But gestational diabetes, this is a scenario where a patient, the diabetes was first, the glucose intolerance was first recognized during pregnancy. So they didn't have it prior to being pregnant. And oftentimes this is the result of hormonal changes that can increase insulin resistance and whatnot. And these patients will typically be assessed for risk and if found intervention, their first prenatal visit. But it's something that is definitely monitored for throughout the pregnancy. And if the patient does have gestational diabetes, ideally we would try to get them on insulin therapy 'cause we wanna keep really tight control of their blood sugars. And then typically after giving birth, they're insulin or their glucose intolerance. You know, kind of take care of it, you know, of itself. And it resolves what that patient is gonna be able to be more at risk for developing type two diabetes later on. But I just wanted to kind of throw out that run down at the beginning just to kind of differentiate but all of these we will be using insulin therapy and I'm in their own way. - Yep, absolutely. So we'll start with kind of broadly categorizing the types of insulin based on their duration of effect. And as we go through, you'll see that they serve different purposes because of that. So we have rapid acting, short acting, intermediate acting, and long acting, insolence. The rapid acting insolence are Aspart, Glucine and Lispro. So their duration of effect is four to six, five to six hours typically. So if you're looking at it on a graph, they have kind of a bell curve look where there's a short peak or shorter peak and then it moves into that exit period at five to six hours. The short acting insulin. - That peak, it's like within an hour so it's already peaking, which is unique with that one. - And peak's higher than the other. - Yeah, the others. - The short acting insulin would be regular, insulin regular. It has a duration of effect, but about six to eight hours, intermediate acting is insulin in pH 14 to 18 hours. And the long acting, Glargine, 24 to 30 hours, and Degladec, 36 to 42 hours. So as you extend the duration of effect, it's going to last longer, but there's gonna be a lower peak. So it's more of a steady insulin level throughout the time period that it's acting. - Now the big question is, do we miss our, you know, recently discontinued long acting friend insulin deadomere, the leaven mere? - Yeah, I miss it so much. - Yeah, me too. I never had much luck with that, with the leaven mere. I feel like I always ended up having to split the dose, and just, we was cheap at our clinic, so we definitely used it in some patients, but yeah, I was not all that disappointed when I found that it was coming off the market. - No, yeah, all things being equal, certainly the Glargine or Degladec would have been preferred options. - Yeah, yeah, now with the Glargine, there are several different formulations, are our brand names of this, I should say. There are some that are considered, like, you know, true biosimilars, so Lantis. The biosimilars that are the simgly and the Glargine YFGN biosimilar or the Resvoglar, which is insulin deadomere. Glargine AGLR, are, you know, actual biosimilars. The others are like follow-ons, they're called, so they're not technically, you know, exact, interchangeable, like, it's not the orange book for the FDA, but I guess purple book is the one for biosimilars. - I think so, yeah. - So they're not interchangeable by like the FDA standards, although they're clinically, they're the same. But there's all these different formulations, and I feel like it's definitely caused a lot of confusion amongst patients and some healthcare professionals as well. But, you know, Lantis was the Glargine, that was first on the market, and now we have simgly, we have basic LAR, you know, these other generics. And so the one, you know, the big thing is checking with patients' insurances and formularies and making sure that the formulation that you write is appropriate and approved into their insurance because, obviously, depending on the state, pharmacists can't always swap out, you know, they can't swap out the products, you know, one to one unless it's one of the biosimilars, so they're gonna, have to get in touch with the provider and go through the whole process. But I feel like that has caused a lot of delays in therapy. - Oh, yeah. - So, from a clinic standpoint, trying to kind of have, you know, an idea and a game plan for these formularies changes that happened at the beginning of the year and whatnot. But more products, I'm sure, will get approved and more insurance formularies will have there, you know, kickbacks and contracts and whatnot with them. So, the moral of the story is with the Gloria gene, they're, you know, clinically, you can exchange them one to one, but it really comes down to figuring out which formulation the insurance will, or branding the insurance will pay for. I feel like that ends up being harder of a process than actually managing the insulin itself. - Right. - Trisiba is, you know, the insulin deglidic as of now, that's the only formulation. There's a U100 and a U200 formulation, but other than that, that's the only brand name of deglidic. And, you know, also a great option if you need a basal insulin. - Yeah, hopefully with all the generics and biosimilars, the silver lining would be that, insurance is just give less pushback about cost and copays and the prices overall lower. So, doing it whole patients don't have, like outrageous, you know. - Yeah. - Out of pocket costs, stuff like that, but that takes time. - And then some of them, like semmelies, a lot cheaper than some of the others, but then insurance companies will be contracted with basic largely exclusive. - They have that as an exclusive. So it's just like, oh my gosh. - Yeah. - It's been such a pain this year keeping up with all those. - Yep. - It is a pain, it is a pain. So, I mentioned that depending on the duration of action, it's gonna affect how these are used. So the long acting insulin are considered your basal insulin, as would it be referred to as. For type two diabetes, if a patient is newly starting on a basal insulin regimen, there's a few different ways that you could estimate what their initial dose should be. In any case, you'll want to adjust based on the patient's response and how their blood glucose levels fluctuate based on the dosing. One way is to use a starting basal dose of 0.1 to 0.2 units per kilogram per day. So that's one calculation you can do. You can also take their fasting blood glucose, subtract 50, divide by 10, and make that the daily unit dose to start. Or, which many people do this, just to start with 10 units for anybody, and then titrate every one to three days by one unit, depending on the response. Mike mentioned your Siba, go ahead. - I wasn't saying which in the actual practice, which one do you typically use, or do you use a combination of the two? - I mean, I don't initiate, but when I was more involved with it, I feel like the fasting blood glucose minus 50 divided by 10 is what would pop up more often, but I think a lot of people just do the 10 units than they go from there. - Yeah, I feel like I would do the weight base just to kind of get an idea. And then, like, compare that to the 10 units and take somewhere in the middle. It was always my method. But I definitely would try to do the one to two units every three days or so if the patient was really, you know, on top of checking, and then, you know, definitely made it easier to titrate up. But I was, yeah, I was doing the combination of weight plus the lazy man's 10 unit starting point. It's hard to go wrong as long as you're somewhere in the ballpark of one of those. I mean, the only issue is if you just start them at a dangerously high dose, and obviously you don't want to be extremely sub therapeutic and that just delays things. But the only real problem could be if you just started them on a much higher dose than they actually need. - Much higher. - Which could accidentally happen if you got the concentrations mixed up. So, Mike mentioned that Terceba has a U100 and U200 formulation. Most basal insulin are just U100, which means that there's 100 units in every milliliter of liquid. But like he said, Terceba has the U100, but also a U200 formulation. So there's 200 units per milliliter. And then Tigeo has a U300. That's an insulin-glarging product, but it has a U300 version where there's 300 units per every milliliter. What's the purpose of that? Primarily for patients who are on high doses of insulin, just having less liquid that they're having to inject, and that can help with adherence and injections like reactions and stuff like that, I suppose. But if you're not paying attention and that gets mixed up, that can be a big problem. - Yeah, and I think sometimes providers will try to do like the U200, because you get like, I think it's three pens in a box, so you end up getting more like units per box. But they'll do the U200 and then put it. It's like, oh, patients taking 20 units per day. I'm like, well, why are we doing U200? And it's like, it's still a total number of units, so it doesn't end up being that much more of a savings, but I just think that's funny. And I know what we'll do. - And you'll have many pharmacies that break the boxes. And the bigger pharmacies I imagine are doing that. - They're getting audited and they gotta break the boxes and it makes no difference from that perspective anyway, so. - Yeah, definitely insurance companies do not want to be paying for extra insulin for nothing. Now, one of the things when Traciba came out was because of its even longer duration, then Lantis had a true 24 hour duration, but this insulin diglitech now is up to 42 hours. One of the concerns was, as the patient gets established on their dose, because it's longer than 24 hours, are we gonna start getting insulin stacking and eventually have a much higher risk of hypoglycemia? But there's actually been a couple different studies and one in particular, the switch to trial was evaluating for hypoglycemia in patients they were either on insulin diglitech compared directly to insulin-glargine. And believe it or not, the diglitech actually had less instances of hypoglycemia. So that was an interesting finding, but it does seem to give maybe a little bit better, it's more stable background support of insulin. But again, a lot of it comes down to patients' insurance and things of what they can cover. But I have, you know, kept that in my back pocket before if a patient's having a hard time with, they're fasting, blood sugar's dropping a little too low, switching them to Traciba and had a little bit better luck. - Right, right. You didn't talk about trowels yet. - That's a great, yeah, I just switched you, I mentioned. But that's a good segue into over basalization. You wanna jump into that so on? - Yeah, I'll give kind of a definition of it and I know Mike has a lot of thoughts on it, so I'll let you get the new gritty. But we've talked about it a couple times before, I think about what over basalization is, effectively it is, a patient who have are getting too much basalence lung and it is affecting their A1C control, diminishing their A1C control, really. And they're not able to meet their glycemic targets because of it. They define it as the use of basal, a basalence lung dose exceeding 0.5 units per kilogram per day in a patient whose A1C remains above their goal which frequently that's used, 8% is used in this instance. This definition is recognized by American Diabetes Association. So we mentioned this, I'm pretty sure in April when we were talking about the updated guidelines, which recommends that clinicians should monitor for signs of over basalization actively as their dose approaches the 0.5 unit per kilogram per day threshold. They've almost backed away from the threshold now because they have some studies showing that it's maybe even lower, so they're having some showing higher. So they're really focusing on the symptoms of over basalization more so than, like I said, that 0.5, a lot of places will still kind of use that number. I kind of have it in my head as well, but they do the new ADA updates this year, we're kind of pushing towards the symptom control and monitoring for signs and symptoms versus a set glucose or insulin, you know, total daily dose, which I thought was interesting. - Yeah, that is interesting. And also as far as how many patients this affects, it's kind of, they're unsure, there was one observational study that showed in one hospital, it was about 6% of patients, but in other studies have reported much higher rates of like 30 to 40%. So they're not sure how many people this affects, but certainly should be something that should be talked about and one something I was aware of before we started talking about it in the last few years, I think. - Yeah, and you know, it's one of those things where the patients fasting sugars may be controlled, but the A1C is high. And so the clinician may continue to increase the basal dose of, you know, insulin, maybe they're not on brand deal control or, you know, they're not on a GLP1 or what have you. And so it's most likely they're post-prangial readings that are actually elevated and need to be addressed. But the basal dose continues to go up. You know, there's lots of different ways that this can kind of, you know, sort of slowly occur without, you know, being, you know, it's something that was intended or what have you. But I've definitely seen plenty of patients who have been managed, you know, over the years, and their basal dose has just slowly gone up to the point where they're on like 70 units twice a day, as a type two, and their A1C is still not controlled. And so that's, you know, it should be a huge warning sign that some basal over basalization might be occurring. And so some key things to kind of consider, you know, the basal dose and A1C. So again, that greater than 0.5 units per kilogram per day has been historically what we've used, and especially in patients whose A1C is over eight, like Cole mentioned, you know, even though the ADA has kind of pushed back on that, you can still kind of have that in the bag of your head, I think, is sort of just something to keep a lookout for. But one of the ones that the, or parameters that the guidelines do mention is the bedtime to morning glucose differential. And so seeing like a large drop in blood glucose from the bedtime reading to the fasting morning reading, you know, definitely can be a sign of over basalization and then comparing fasting versus post-prandial discrepancies. So one of the big things with over basalization is you'll see fasting sugars that are in the right range, you know, 80 to 130, but the A1C is still elevated. And it's usually because those post-prandial spikes are much, you know, higher than we were anticipating but you know, not being addressed properly. If the patient is experiencing over basalization, they oftentimes will have like this, you know, quote unquote rollercoaster effect. Yeah, the excess of basal dose pushes the glucose lower during the fasting periods. And then the patient is not having controlled post-prandial spikes, that sends it really high again. And then it's just these extreme highs and lows and you know, this really high glycemic variability. And that just sets the patient up for failure. And then also obviously the patient's having with current hypoglycemia. You know, it doesn't have to, it can be symptomatic or asymptomatic but if they're having frequent episodes, especially overnight or you know, happening during fasting periods, that was probably a result of excessive basal dose. Right. And so again, so it doesn't mean that you know, the patients may not be on some higher doses than average for basal insulin. But if you start seeing some of those symptoms, you know, they're A1C's not being controlled, definitely consider back in that down and attacking those post-prandial readings instead. Yeah, no, it's interesting because it's probably not particularly uncommon for maybe the fasting blood sugars looking okay, but they're A1C's high. Maybe they're only on a basal insulin regimen and they don't want to add on extra injections, right? So they keep pushing the, because you know, let triggers looking okay, we just need to get that A1C down so they keep pushing the basal dose, but that's not addressing the post-prandial spikes. Pretty much all, and so they're having this problem. So it's, I think it's well intended 'cause you don't want extra medicine and extra injections, but in that case, they need the post-prandial control specifically. Right, yeah, that's, I mean, at least again, in my limited experience, that's the situation that usually occurred that led up to it is like, you know, they were trying to do right by the patient, but not give them extra meds. Right, right, but mechanism is important. Yeah. Yeah, interesting stuff, interesting stuff. Okay, so that's the long-acting insulin. It's a lot of considerations there. Moving on to the intermediate and the short-acting insulin. So the intermediate brain names would be, the intermediate insulin in general is the insulin in pH. So there's humulin in, there's novolin in. I mentioned the duration of effect is 14 to 18 hours. These are both human type insulents. Then the short-acting insulents would be the regular insulin. Humulin R, U100, humulin R also has a U500 concentration and the novolin R. Six to eight hour durations except for the U500 humulin has a longer duration of 21-ish hours. It's a pretty wide range, 13 to 24 hours. These are human type insulents as well. Yeah, I think the U500 is definitely going to be safe for your type ones that are probably on like a palm or something like that. Right, right. Not something you see all that often. They for a while they had, they may still have, and I actually haven't looked in a while, but the auto injectors, the pens for the U500 had like increments of five units. It's a, you know, patients who had really high doses, but yeah, I cannot tell you the last time I saw someone on U500 that didn't, you know, have a palm or something. Yeah, it's a half to concentration. It's a half to concentration. Now, the reason why these still come up because we tend to think of these as being, you know, lower grade insulin, if you will. I don't know if that's the right terminology for it, but just not as easy to use as some of our new synthetic insulin is like our basic. Not as good of a rapid acting. Yeah, plus the more inconveniences for us timing, you know, with meals and all that. But these do tend to be, you know, cheap, if you're talking about just average wholesale price, you know, and what's the cash price would be for a patient who doesn't have insurance or something. These historically have been the go to insulin because of their lower cost. You know, I will say nowadays there's enough patient assistance programs, you know, FQHCs that have, you know, 340B programs, other, you know, entities that have 340B access and their pharmacies. You know, there are a lot of programs that can give patients access to these brand name and, you know, better insulin. These synthetic insulin. So I feel like it's kind of few and far between the patients that still need to be on the NPH or the regular human insulin. But definitely still out there and, you know, still need to be familiar with them. But think of NPH is like the basil, you know, side of things of the two. So NPH, like Cole said, has kind of a range, you know, of durations. But typically, you know, to get a full coverage, you know, 24-hour period, you dose it twice a day. Some patients can't get away with once a day. But twice a day is often seen and that's, you know, kind of like our basil coverage. So managing our fasting, our blood sugars, you know, it first wake up in the morning or prior to a meal. And then the regular human insulin, the short acting insulin is the human art, novel art. You know, ideally taking about 30, maybe even up to 60 minutes prior to a meal, because there is a little bit of a delay when then until they get their, you know, peak concentration of insulin. And so timing it, you know, to make sure that the insulin starts to peak is the patient's, you know, food is starting to be digested and would be ideal. But, you know, patients tend to have a hard time either timing that correctly, you know, misjudging that 30, 60 minutes in some cases or something comes up during that time period and they end up not eating. That puts them at high risk for having to hypoglycemic event. And so definitely some issues and some difficulties they can come up with using these insolents. And like I said, lots of good opportunities for patients to get on newer in, you know, synthetic insolents that are a little bit easier to use. But these are still out there and can definitely be useful in some situations. - Yeah, the uninsured population where GLP ones aren't as easy of an option as definitely where I see that, which certainly most of them have patient assistance programs where it can be facilitated. But sometimes I guess the, you know, the clinics might not have the staffing or knowledge to facilitate that or sometimes the, there's just some trouble getting the patient to, you know, get the paperwork through because sometimes there's some stuff to fill out and get in. So sometimes it's hard to get a hold of them and get the paperwork back. And so this might just be the, I've had people just not want to do that and go with a different cheaper option just because they don't want to go through that process. - That hassle, yeah, for sure. - So, you know, you still certainly get that. So the other options are the rapid-acting insolence and the ultra-rapid-acting insolence. So these are going to be considered more of your Prandiol type insolence that we were referencing before. For the rapid-acting, we have Lisbro, Aspart, and Glulacine. It's the brand name for Lisbro or the brand name. So our Humalog as well as Admelog, four to six hour durations. These are insulin analogs, not human insolence. Novalog is insulin Aspart, five to six hour duration. And Apedra is insulin Glulacine, five to six hours. The ultra-rapid-acting insolence would be insulin Aspart and then a modified insulin, Lisbro, has a designation of A, A, B, C. It's one of those designations. You usually see with a biosimilar. I don't think this would be considered that. I think it's just some different form of it. But fiasm is insulin Aspart and Lyomgev, if that's how you say it, is the ultra-rapid insulin Lisbro. Both of these have a four to six, five to six hour duration. But they have a faster onset. Is the difference there? Yeah, and there was some discrepancy. When we talked about fiasm, I guess at the last-- it was either the panel discussion or something similar to that that we were doing. But somebody brought up that fiasm was no longer on the market. And I believe at the time when we looked it up, that's what we thought as well. But I just looked at it last night and it looks like they had some manufacturing issues, I guess, at the beginning of the year, but seemed to be resolved. And so I guess they are keeping fiasm on the market. Is what it looks like for now? But it's kind of confusing, because I feel like they've kind of flip-flops, but I even talked to a drug rep a couple of weeks ago and asked him, he's like, no, they're not discontinued that I'm aware of. So I'm assuming that it was just that maybe they thought they were going to discontinue it because of the manufacturing issues, but that got taken care of. But it seems to be that it's going to be on the market. But stay tuned, because I mean, with the way things have gone, don't hold us to that, because it could change easily. We just say what we see. Yeah, yeah, yeah, and it's hopefully we don't misread. But the-- like Cole mentioned, these are considered rapid acting insolence, because they definitely have a faster onset of action. Typically, if we're talking about the textbook answer, taking it 15 minutes before a meal would be great. But in most cases, the onset of action is quick enough with these that you can actually take it right before you start eating, and then just kind of go on with your meal. That just cuts down on the issue of having to time the dose and worry about something coming up in between that time, where you don't actually start eating when you think you are. As far as the fiasco gives, and the reason why we talked about that and spent some time addressing it is-- like Cole mentioned, it's an in-sport derivative. But it's got a vitamin B3, a niacinamide derivative that's also added to it. And that increases the speed pretty substantially for the insulin to be absorbed. And the onset of action, this is as short as 2 1/2 minutes. And so this is something that, from a drug-approval standpoint, can be doseed. At the start of the meal, up to 20 minutes after the meal and still be effective in maintaining those post-prangial spikes. So I can say that I've used this one time in a patient who was-- I mean, granted they had a history of very severe hyperbolecemia like where they had blood sugars like the 20s or 30s, and they were unconscious, and pretty scary stuff. But it was just absolutely terrified of having a low. But their A1C was pretty high, and they were skipping their doses of insulin at various meals. And it was really coming down to that fear of hyperbolecemia in the timing of it and all that. And so we talked about fios, but how you can take it after you eat, so you know for sure that you've consumed the meal and blah, blah. And the patient was very excited about that and got approved, and the patient said when he started improving. So I have some where this can play a role. It definitely not a common situation. But I like when we get something in our toolbox for those kind of off-the-wall situations. Yeah. It's nice to have that as helpful. But yeah. Errors in the quiver, as I like to say. Yeah, so you do like to say that. Sardines in the Sardine can. Yes. A bunch of examples of this. It's plenty. I mentioned admalog, which is, like I said, insulin Lysopro. And we've thrown around the word biosimilar a lot. It's not considered a biosimilar. It's considered a follow-on. So, you know, for any practical purpose, it doesn't matter. But terminologists just say, you know that. Yeah. There's also people who really care, they really care. So here's the right term. It'll pop up at a pharmacy trivia night sometimes. Conferences and stuff. Right. We did not mention the mixed insulin. So there are mixed insulin. There's like novelin 7030, humulin 7030. And what that means is it has 70% in pH insulin and 30% regular insulin. So you're getting kind of both a bit of a basal and bolus together. Their formulations are cloudy. The humulin is available in a quick pin. There's also a novelog mix, 7030. It's 70% in pH and 30% aspart insulin. It's available as a flex pin, also a cloudy looking formulation. And then there's a humilog mix of 7525 or 5050. And that is 75% in pH and 25% in Lisbon or 5050 in pH and Lisbon. Also available as a quick pin and a cloudy formulation as well. Do you want to do the password before we move into some kind of place and there be for insulin a little more specifics on that? Yeah, yeah. So the password for the post activity test today is just going to be insulin. So IN, S-U-L-I-N, all capital letters, no numbers or anything this time. Just insulin. And that is again on freec.com's website. You go to the Learn tab and look, there's a heading for podcasts and find this episode. And that's where you put the password to access the post activity test. It'll be on freec.com's website. So that's again, if you have unlimited membership, you get access to not just this episode, but all of our uploaded episodes. And if you're not, check them out, see what you think. And I think it, regardless of what your style of learning is, you'll find something that suits you. Yeah, I'm glad we're not doing a number on this one because sometimes we get people with like adding the 25 at the end, and I guess in their head they type out 20, 25. And so we get the occasional email where, you know, the, you know, like it's the password right. Did we say it wrong in the episode? I'm always like, "Oh, did we say it wrong in the episode?" Somehow we seem to be 100% for saying the right password, but the 25 people sometimes just add the extra two zero at the front and at the horizontal. And ask us if we keep a thorough list of when we actually say the password time. Whenever it has to be verified, one of us has to go back and listen to the episode to find where we said it, because we know we do not keep a list. I mean, that's the most preposterous waste of time ever, is the fact that we don't just mark the time. We'd take the almost effortless and yet we don't do that. Or write it down. I guess even if we wrote it down, we'd have to go back and listen to make sure we said the right thing. And marking the time would make a lot of sense. Yeah, but to our suggestion box and see if it's going to run to it. Our self-suggestion box. Yeah, our self-suggestion box is internal. Nobody else can suggest things. It's just right. We don't accept outside recommendations at all. The problem is getting to these old suggestions. We say we're going to do them and then we just talk about them. Right. And then the episode's over. We forget what we talked about. That's a good point. Or at least I forget that we talked about it. But that's neither here nor there. We'll figure out that on our end. That's not for you all to worry about. Let's kind of talk about how we can put some of this together. And we'll talk about it from a type 2 diabetes standpoint first. So if you have a patient, there's a few different situations where you may jump kind of right to insulin or at least considering an injectable. The patient's A1C at baseline is greater than 10%. If their blood glucose is 300 or more, they have the classic polys, unexpected weight loss, symptoms of hyperglycemia, it may be something that you can actually, at least for a short period of time start a basal insulin in these patients or at least an injectable. Now they prefer injectable just across the board. As far as the different options are out there are actually the non-insulin products, the GLP1 receptor agonists or the GIPGLP1, dual agonist, the monjaro. In most patients, those are actually preferred over insulin. As far as the hierarchy when you're starting these therapies. The patient is already on one, if the patient doesn't have insurance that covers it, the high deductible, whatever. Even in some cases, if you're starting a GLP1 at a low dose and the patient has that high blood sugar, sometimes you'll do a basal insulin almost like a bridge therapy to give you some time to bring that sugar down while the GLP1 dose is going up to the therapeutic range. But if we do make the decision that we're going to go with a basal insulin therapy, we're moving that route. We can either do a true basal insulin like with the analogs, so that the glargine or delodac, or we could use a bedtime and pH dosing as well. Obviously, that depends on the patient's insurance coverage and all that good stuff. The MPH is going to be the cheaper of the two. Like we mentioned, there's a few different strategies for starting doses. Like I said, I do a 10 unit on one end of the spectrum and then the weight-based 0.1 to 0.2 units per kilogram per day. On the other end, I take somewhere in the middle as my starting dose. I either bring the patient in for a close follow-up to make some adjustments myself, or if it's a patient that is more comfortable with checking their sugars and monitoring their fasting levels, we'll have them go up one to two units every three days or so. We see their bloc glucose and irregular basis fall in that 80 to 130 fasting range, and then we can keep them there. Now, at that point, if the A1C is on target, perfect, that's great. If it's not, but their fasting blood sugar is at goals of 80 to 130, we definitely would want to start doing some pre-prandial or post-prandial glucose checks and try to see if it's the post-prandial spikes that's causing it, because we don't want to start increasing that basal insulin and causing the chance of over basalization occurring. We want to keep in mind that there is eventual plateau effect, if you will, with the basal insulin for our type 2s. We don't want to just keep going up and up. We want to watch not just A1C, but also the fasting levels that we're getting. If the patient's A1C is not at target, though, obviously depends on where the bloc glucose excursions are occurring. One option would be to increase MPH if you're only using it at bedtime, you could increase it to twice a day to make sure you have full 24-hour coverage. If you're using a basal insulin, like the Glorgene or something like that, Cole, do you want to talk about what you can add on to that? Yeah, we're moving on to that. Yeah, well, I'm at the ad-prandial insulin box. Yeah. Usually, you'd want to start with the largest meal or the meal with the greatest post-prandial glucose excursion. Insulin can be dosed individually or mixed with MPH depending on what's appropriate for the patient. One option to start is with four units daily or taking 10% of the basal dose and going from there. If the A1C is less than 8%, consider decreasing the basal dose by four units daily or by 10% of the basal dose when you're adding on the prendial insulin. As far as titrating, you'll want to increase the dose by one to two units or 10 to 15% depending on what that is twice a week. If they're symptomatic and they have hypoglycemia that occurs for no clear reason, just consider decreasing the dose and see if that fixes it by about 10 to 20% and see if that helps. If A1C is still above target, you can step wise, add additional prendial doses. You can go to two doses a day. If it's still above target, you can move up to three doses a day. You can do a full basal bolus regimen, basal insulin plus bolus insulin with every meal that they have. That's where those mixed insulin can come into play. Right. You can consider a self mixed or split insulin regimen. You may adjust NPH and short or rapid acting insulin separately. If you're going to start that, you could take the total NPH dose being equal to 80% of the current NPH dose with two thirds given before breakfast, one third given before dinner. You can add four units of short or rapid acting insulin to each injection or 10% of the reduced NPH dose and you would titrate the components of each regimen based on the individual needs. Or considering twice daily pre-mixed insulin, typically to start, you would do unit per unit of the same total insulin dose. If you're going to do that, it may require adjustments, of course, based on the individual patient's needs. But one of the main takeaways I do want to make sure we harp on is, you know, if a patient's on a basal regimen, they need prandial insulin. Like Cole said, start with the largest meal and kind of give them a few months to see how they respond with covering that meal. I cannot tell you how many type 2s I've seen go from basal insulin once a day to having one visit next to you know, they're on a basal insulin once a day and then three doses of prandial insulin right from the start. Unless it's a type one, like there's a lot of times we don't need to jump to that, you know, extreme of coverage, but you can add on the subsequent meals as you go. And then like Cole said, there's lots of ways for mixing and matching. If you're using MPH or, you know, what have you, but the moral of his story is oftentimes consider taking away a little bit of the basal dose to add on the prandial dose and not just again stacking the insulin, you know, so it all depends on how much room the patients A1C has, but if you're interested in like a pretty, what I think is a pretty solid flow chart of all of this, if you check out our long term friend, the show Pearls, one of his diabetes sections that he has for the diabetes pharmacotherapy has a flow chart out of the treatment algorithm and it walks through this step by step and all of the various different, you know, options at each stage and very aesthetically pleasing to the eye as well. So it's basically kind of following the ADA guidelines, but it's their Pearls version of it. So check them out. They have a lot of great content as well and it's much easier to follow when you have something in front of you. Yep. Agreed. Agreed. The other thing I want to touch on and then we'll finish up with some type one calculations and things to consider, but we talked about adding prandial insulin. So obviously when you were injecting prandial insulin, that's covering for the carbohydrates that you're about to eat for that meal. There's something called a sliding scale that will be given to patients that will help to kind of correct the sugar if it is high going into the meal and then hopefully, you know, they will, it won't be elevated to the next meal. The problem is is that sometimes patients are giving a sliding scale without any sort of base coverage for their meal and, you know, meaning that a sliding scale may look something like, if your sugar is 150 to, you know, 199 add two units. If it's 200 to 249, then add 40 units. If it's 250 to 299, you know, 16 units and so on and so forth, it goes up, you know, every 50 milligrams per decilator goes up to 2 units. But that's starting it, you know, patients blood sugar is 150, you know, at the start of the meal. It's going to go higher assuming that they're having carbohydrates with their meal. And so there's really, you're correcting it, but then pushing the sugar right back up beginning because there's nothing to cover, you know, the actual meal itself. And so making sure that if you do use a sliding scale, you have the sort of base coverage that's going to cover their meal. And the sliding scale is adding on to the base, you know, to make sure that if you cover or correct rather the high blood sugar going into the meal, but that that base dose is there to actually treat the meal, you know, post-prandial spike itself. So to give you like a, you know, example, you know, the patient's dose is five units with dinner. They check their blood sugar before dinner, they're, let's say it's 267. So according to their sliding scale, they would add 16 units, so they're doing their five units, which is their base, plus the six for the slide. And so they're doing 11 units total. And that should hopefully correct and cover their meal. And hopefully the blood sugar will be good going into the next meal. Yep. But I've just seen a lot of sliding scale insolence that don't have any sort of base coverage along with it. So just more to make sure we talk about that. Yeah. That's important. Okay. So we're going to finish up talking a little bit of math because type 1 diabetes, since you're having to use insulin pretty much no matter what, you got to do a little bit more math. It's not crazy math. It's not too bad. I promise. But we'll try to break it down in a way that's hopefully easy to understand. So when thinking about initiating insulin, the American Diabetes Association suggests generally starting the total insulin dose around 0.5 units per kilogram per day. But a maintenance dose can range anywhere between 0.4 to 1 unit per kilogram per day. Generally they recommend using 50% of the daily insulin dose as basal, and then 50% as perandial, with the perandial doses divided amongst the meals. It'll vary by patient. You'll have to adjust things. This is just kind of a baseline to start. So an example of what this would look like for a patient who weighs 84 kilograms, let's say. So they weigh 84 kilograms. It's going to be 0.5 units per kilogram per day. That's going to be 42 total units of insulin per day. So we're going to divide that in half for the basal and bolus components. So that would mean 21 units would be their basal dose. 21 units would be used as the bolus doses, but it'd be split amongst the perandial doses. So you would divide the total rapid-acting insulin by three, assuming the patient has three meals that are similar in size per day, which would mean that each rapid-acting insulin perandial dose would be seven units. How was that, Mike? I liked it. Too complicated. That was good. Thanks. Thanks. For those of you who didn't follow on, go back, listen to it, and actually write it out. Write it out. Show your work. Remember that. No. You had to show your work, or you didn't count like, okay, this is nonsense. Do you want to touch on quickly some ways that we can adjust insulin, you know, doses, meal to meal? So there's some things that can kind of individualize the patient's dosing. So the insulin to carb ratio, and then also the insulin sensitivity factor, or a correction factor, as it's referred to. So the insulin to carb ratio is used to determine the number of grams of carbs that would be covered by one unit of insulin for the patient. And so it's used obviously with carb counting, which is going to be something we may do with type 2s, if they're really insulin resistant and insulin dependent, but mostly seen with our type ones that are dealing with this, you know, for their whole life. And there's a few different formulas that we can use to kind of calculate grams of the insulin to carb ratio. So if we're using regular insulin, like human insulin, there's the rule of 450, which is basically just 450, the number of 450 divided by that patient's total daily dose of insulin. And that's going to equal grams of carbohydrates covered by one unit of regular insulin. With rapid at the insulin, we use something slightly different, we use the rule of 500. So same concept, 500 divided by total daily dose of insulin. And that's going to equal the grams of carbs covered by one unit of the rapid at the insulin. So the equation is slightly different based on the type of pran deal insulin that you're using. And so again, to give you an example, and these are actually full disclosure, the examples that the purls uses on their insulin section of their pharmacotherapy for diabetes. So again, check this out, and you can see this all written out very nicely. But if a patient is taking 26 units of long acting insulin, eight units of rapid three times a day, so they're essentially 26 units plus 24 units of the pran deal. So that equals 50 units total. If we use the rule of 500, because it's rapid acting insulin at 500 divided by 50 equals 10. So the patient's insulin to carb ratio is 10, which one unit of rapid acting insulin will cover 10 grams of carbide rates. So if the patient knows their meal contains exactly 60 carbs, and ICR is 10, they can do six units of insulin and cover that meal exactly. And you obviously have to very motivated patient to follow this, but you can get really tight control of your sugar if you have the patient willing to do that. And then the correction factor is again kind of used, is a correction dose when the blood glucose is higher than we would ideally want it. So the insulin, the correction factor is how much blood glucose will be lowered by one unit of insulin essentially. And the calculation wise, we can either use the rule of 1,500, which is used for regular insulin. And that is 1,500 divided by the total daily dose of insulin. And that equals a correction factor of one unit of regular insulin. And then the rule of 1,800 is what we use for rapid acting. So 1,800 divided by the total daily dose of insulin. And then the correction dose is determined by subtracting the patient's current blood glucose by their target and then dividing it by that correction factor. So if the blood glucose is, you know, the blood glucose is 180, but it wants to be 120. We divided by that patient's calculate. We use the rule of 1,800 to calculate their correction factor, ends up being 15. We would be able to determine at four units of insulin is what we need to add to correct for that sugar. That's basically taking a sliding scale and making it extremely, you know, patient-specific and narrowed down. So again, the pearls, pharmacotherapy or diabetes section for their pharmacotherapy, charts and whatnot has a great section on this and breaks it down very simplistically. But this is going to be saved for a patient who is very motivated. And I will say a lot of the type ones that I work with even are not this precise with their insulin doses. Eventually, hopefully, you know, would like to get them there, but not there yet. So yeah, this is for a very specific type of patient who is very experienced. So I don't want to say this wrong because this always makes my head spin a little bit. But so the patient can use the insulin to carb ratio to determine what they need to inject for that meal that they're about to eat, and then the correction factor is what they're adding on top of that, depending on what their current blood glucose is before they eat. Right. Yeah. Perfect. Perfect. But I know that's a lot, I know it's really hard to probably follow if you're just listening. So like I said, I encourage you to either look up those, the rule of, you know, 1500 rule of 1800. It's fairly easy to find online and kind of look through it, you know, on your own to kind of see what we're talking about, and I think it'll make a lot more sense once you see because it's pretty simple math. It's just a matter of keeping track of what's what. Right. Right. But if you want to be like, you know, the certified diabetes, you know, care and education specialist, that is something you'll have to be familiar with for at least a very small portion of the exam. You should don't have to do all those calculations because there's some of that on there. Yep. That's right. It could be on there. I guess there's multiple versions of the test. I'm sure. I met them. That's a pretty standard thing to have at least some sort of insulin calculation, right? Yeah. They're sure. I would think so. I don't think so. But that being said, anything else that we want to go over, I think we're almost at a time. That's all I got, ma'am. All right. So for those of you who, again, are free seat members, make sure you snag your one hour or continue education credit, at least for the pharmacist and nurses. And we thank you to give a big thank you to free.com for continuing to partner with us again. Big shout out to our friends over at purls, continuing to make a great platform for drug information, and they keep adding great stuff. So you can check them out purls.com/coreconsultRx. They've been a long time sponsor and friends supporter of the show, so definitely, you know, support those who have supported us if you can. And if you want more structured lecture style podcasts, make sure you check out our Patreon. It's patreon.com/coreconsultRx and we have a bunch of different pharmacotherapy lectures. And I know we've been a little bit slow, or I've been a little bit slow, but posting new lectures on there last month or two, and we have some good stuff coming up probably in the next couple weeks. So make sure you check that out. And if you have any questions, comments, concerns or anything for calling myself, definitely reach out to us over email. We'll do our best to get back to you as quick as we can. And then other than that, you know, I don't have anything else cold to you. That's all I got to do. All right. Well, we appreciate you guys so much for listening to us, and we'll see you all in the next episode. Have a good one. [Music]