Speaker 1 00:00 Alex, welcome to HelixTalk, a podcast presented by the Rosalind Franklin University, College of Pharmacy. We're hoping that our real life clinical pearls and discussions will help you stay up to date and improve your pharmacy knowledge. This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - Dr. Abel 00:29 And now on to the show. Dr. Sean Kane 00:31 Welcome to Episode 34 of HelixTalk. I'm your co host, Dr. King. I'm Dr. Schuman, and I'm Dr. Patel. This week we're talking about some newly approved insulin products that have just made it to the market. Speaker 2 00:42 So namely, we're going to be talking about Toujeo that's glargine u3 100. Humalog u2 100, and very recently approved degludec, which is available as u1 100 as well as u2 100. Remember, Afrezza is also a new insulin, but we've talked about it already in Episode 16. Dr. Sean Kane 01:02 Ludaku Patel, when you say you 100 you 200 and you 300 what do the numbers mean? Speaker 2 01:07 Basically, these are the strengths of your insulin. So that basically means that there are 300 units of insulin per one mL of this Toujeo same thing with Humalog, there is 200 units per one ml versus the traditional ones. The u1 100 is 100 units per one ml. So you're talking about a little stronger insulin, if you would say so. Dr. Sean Kane 01:31 So then most of the insulins on the market before these guys came out, almost all of them were u1 100, right? Speaker 2 01:38 That is correct, besides the fact that regular insulin was available as you 500 to begin with, but now you're going to be seeing all these new strains because the original u1 100, either it's near to its patent exploration or manufacturers done making money, and they want to make money on the new prototype. Speaker 3 01:57 Yeah, I was about to ask you what the reason was for, but it sounds like you answer it that there may be a little bit of an idea about kind of rebranding or holding on to some of those patents Speaker 2 02:06 that is true. And over the time, as we are learning more about diabetes, we're finding out that, especially for type two diabetes, thinsulin resistant is too much, and some patients are on 300 400 units of glargine a day. You can imagine how much volume they're injecting per day. So using a little bit stronger insulin, like you 300 they might be injecting little less volume, comparatively Cool. Dr. Sean Kane 02:30 Well, why don't we kick it off with the first agent you mentioned Toujeo, which is Glargine u3 100. Can you tell us a little bit more about this agent? Speaker 2 02:37 Sure. So it is a long acting like the name says glargine, long acting insulin that was approved in February. It's for the use for basal insulin. We talked about the concentration as well as 300 units per ml. But there's no vial syringe form available. It's only strictly pen. So Toujeo pens, they're on this like tan, green color pens available, and it's 1.5 ml pen. So total units you're gonna get, it's 450 units. Speaker 3 03:06 Now, one of the first things I think of when we talk about these ultra high concentrated insulin is maybe some of the risk for accidental dose errors. If you were to draw it up with a vial, for example, with a very large amount. So is, I assume, then that was kind of the thought between restricting it to just a pen, Speaker 2 03:22 absolutely this is kind of wrapping around with patient safety and making sure that you're not injecting, because insulin is according to ISMP, one of the medications that's on high alert list, and so we have to be really careful with dosing. So by keeping one formulation and having the built in titration, just click in click on you can minimize the errors. Dr. Sean Kane 03:43 And for the audience that doesn't know, when you have a syringe that used for insulin, it actually has kind of a built in concentration assumed for the syringe. So a typical insulin syringe is going to be for a u1 100 insulin. And you can actually draw, let's say, 10 units, which would correspond to a certain number of MLS. And if you mess with going from u1 100 to u2 100, then what is on the vial or what's on the syringe won't correspond with the actual dose that you're giving correct. Speaker 2 04:11 And let's say you're mathematically savvy, and you will be able to do that conversion. But you have to think about it that the syringes are calibrated two units versus the vial. You can calibrate one unit even you know so, right? Speaker 3 04:25 So when I think about a lot of my patients who have either, you know, a fair number, who have potentially used insulin as a potential suicidal gesture or a suicidal Act, as well as those who have cognitive impairment, you know, those with schizophrenia, bipolar disorder, who are getting these medications, maybe for long standing diabetes, or maybe even for some insulin resistance related to their medications. You know, you're just playing with fire when you when you talk about just handing somebody a big bio and say, now go take care of this on your own. Speaker 2 04:51 Yeah, and I think when it comes to vial syringe versus pen use, besides the safety point, it's, it's just about comfort, patient comfort and. Inconvenience as well. Europe has long gone forgotten the vial syringe practice. I think United States is where probably the vial. So just a little bit more over the pen. When you think about globally, Dr. Sean Kane 05:11 that's interesting. So when I think of different insulins, I mean insulin that is insulin glared gene works similarly in the body to any other insulin, but usually it's the kinetic profile that differs Speaker 2 05:21 absolutely correctly. Yeah. So when you talk about insulin, it's pretty much the same molecule, but the way they have designed it, it gives us a different pharmacokinetic, pharmacodynamic effect, and that's how they're different. Dr. Sean Kane 05:33 So what is it about Toujeo that is different than, let's say, glargine? Speaker 2 05:37 So the onset of action action is a little bit longer. So with Lantus, we get the onset within three to four hours. With Toujeo, we get it somewhere about six hours post injection. If you Dr. Sean Kane 05:49 think about how we're using this product as a basal insulin, it's not that big of a deal that we have this later onset of Speaker 2 05:55 action, right? That's true. So even though we get the delayed onset of action. When you think about the duration of action, it's a little bit longer than Lantus. So we say Lantus is about 24 hours, and this one goes beyond 24 hours. They say about 32 to 35 hours is the half life or, I should say, duration of action. Speaker 3 06:17 So given that, if we're converting a patient, say, from our Lantus to her, Toujeo. What are we doing? Do we need to do a dose change to reflect that? No. Speaker 2 06:26 So like I said, it's concentrated insulin, so you'll be injecting less volume. But when it comes to conversion from either glargine to Toujeo, it's one to one conversion. So it becomes easy, because what they have done in the market, Lantus is still available. They're not pulling Lantus out of the market because some patients might be on a very small dose and not require you 300 but I work in a clinic, and I used to get Lantus samples for, you know, economically challenged patients, and now they're saying we're only going to give you Toujeo pens, you know. So if I have a patient and I want to teach them how to start taking insulin, I may be able to go ahead with Toujeo pen and teach them how to do it, but let's say, you know, they go out and get a prescription. Insurance doesn't cover Toujeo covers Lantus. It should be okay for them to switch back to Lantus, because the conversion is easy. Dr. Sean Kane 07:19 Just to be clear, the generic name of the drug, between Toujeo and Lantus, is still the same thing, insulin, Glargine, right? Unknown Speaker 07:26 That is correct. It's glargine, just the strength is different. Speaker 3 07:29 That'll be something important, though. For again, once we become more familiar with these to where we're no longer using the brand names and the writing, it's something to be careful in terms of, you know, again, those errors and transcribing orders. Dr. Sean Kane 07:40 Unfortunately, because it's a pen, you know, you're still dialing up a certain number of units, and it is a one to one conversion, like you said, Dr. Patel, but the downside is that kinetically, they are a little bit different, and that could potentially lead to issues down the road in terms of patients accumulating different rates and things like that. Speaker 2 07:56 Yeah, that definitely is to be kept in mind. So if you look at a few studies that looked at pharmacokinetic and dynamic you would see they compare what happens to the insulin in the body after one injection and what happens to the insulin in the body after multiple injections. So multiple injections, think about reaching steady state. So what they found, and the ultimate efficacy point for these insulin or any anti diabetic, is glucose lowering effect? How much you know, one unit of Toujeo is going to decrease my glucose by how many points? So what they actually found is after single dose injection Toujeo gave us 12% lowering of glucose compared to Lantus, which is a little bit less than Lantus is, and then with multiple dose injection, they found that glucose lowering was 27% compared to a little bit higher number of Lantus. So what they're saying, because it's fairly new in the market, and you know, if your patient is using Toujeo, they're recently converted from Lantus to Toujeo. But manufacturer says that over the period of time, the patient might need about 15% more Toujeo dose compared to Lantus to get the same blood glucose target levels. Dr. Sean Kane 09:11 So what you're saying is that even though we say it's a one to one in the pkpd studies, you actually may need a little bit more of the Toujeo to get the same effect that you would see. Speaker 2 09:22 That is correct, and it's going to become a little bit more apparent why. I think this is the marketing gimmick when we talk about how it's available, and we compare the availability of Lantus versus Toujeo. Speaker 3 09:32 So then it looks like from I guess the way to think about it is that, you know, if you have that effect, rather than 24 hours, not as much a lowering initially, you almost think of more as a flat, more plot, more consistent profile. So almost looks like even more of a bit to use the word basal, someone more basal than our previous basal, Speaker 2 09:48 yes, and that's where the researchers and the scientists are saying that this gives even the closer representation of a normal pancreas as basal release. So what Dr. Sean Kane 09:58 about efficacy? It's great to talk. About kinetics and dynamics and all that good stuff. But I assume that they had to go through phase three trials. Even though it is the same molecule, it's packaged in a different way. What did we see in the actual clinical trials? Speaker 2 10:12 So what they did to prove Toujeo in the market is they compared it to their very own product, which is Lantus. So they had about a 26 week trial and type one patient in direct comparison with Lantus. To keep in mind, these patients were also on mealtime, and makes sense type one patients, and they found that Toujeo decreased the A1C by point 4% versus Lantus that did by about point four 4% and the baseline A1C was about eight point 12% Dr. Sean Kane 10:41 in both the groups, that's really not that big of a change. But at the same time, they're really not that high in terms of their baseline A1C anyway, so it's not like they had a lot of room that they needed improvement Exactly. Speaker 2 10:52 So if they had recruited patients who had worse A1Cs, maybe this difference would have been a little bit more statistically or clinically significant. And if you look at, you know, their another goal of therapy is to control the fasting plasma glucose, and they found that it was lowered by 17% of Toujeo versus 20% with Lantus. And that's that glucose lowering. In fact, we were talking about earlier, that it's a little bit more with Lantus that comes in handy here, yeah, Dr. Sean Kane 11:16 and I completely agree it's a little bit different. And certainly you may have to bump a patient up, you know, a couple units of insulin. But even clinically, like I don't know that that is a huge difference, you know, between a 17 versus a 20% reduction. That's, you know, 3% absolute difference between two groups. I don't know that a patient would even notice that much of a change, absolutely. Speaker 2 11:37 And then let's take a look at the type two patients. So these patients were in a combination of mealtime insulin plus or minus Metformin to help with insulin resistant and they found that A1C was reduced by point 9% with Toujeo versus point Eight 7% by Lantus. So again, we're looking at pretty much similar A1C reduction, I Speaker 3 11:59 believe, then when combined with non insulin drugs, looking at a 1c reduction of point seven, 3% and then 1.42% again, in two different studies with Toujeo, and that's compared to point 7% and 1.46% versus Lantus. So once again, we're looking at point 03, 2.04% differences there in some of those studies. Dr. Sean Kane 12:20 So in terms of the safety analysis of these trials, they were basically the same as Lantus. But just to reiterate some of the normal points that we would see with either Lantus or Toujeo. Hypoglycemia clearly is going to be an issue. That for any insulin product, for type one patients in the clinical trials, is around six to 7% and then for type two patients, it depends a lot on the characteristics of the patient, how many hypoglycemic agents are on and things like that. So we see a wider range, anywhere from eight to upper 30 percentages in terms of hypoglycemia for type two patients Speaker 2 12:53 and minor cases of respiratory issues like nasopharyngitis and URTIs for up to about 12% were noted in the studies too. Speaker 3 13:02 There are a few other other side effects as well that kind of fit with what we already know about in something that's mechanism of action. So some hypokalemia, so moving potassium into the cells, some weight gain, peripheral edema and lipodystrophy as well. Dr. Sean Kane 13:15 So Dr. Patel, what kind of cost are we looking at, given that it's really, really somewhere for probably the vast majority of the patients, they wouldn't know the difference between the two drugs. Speaker 2 13:25 Yeah. So I think the manufacturer has been really smart with this to make it apparent, because we're thinking, you know, you're using one to one conversion, so I'm going to use the same units up Toujeo. So they kind of kept the prices for Lantus and Toujeo the same. Now here is the trick. You get 13 150 units of Toujeo, because it's 450 units per pen. You get three pens in a package, versus Lantus Solostar comes in pens of five. So the whole box contains 1500 units. So you're getting 150 units less, but Toujeo compared to the Lantus. So that's where you might feel like you're getting gypped with getting Toujeo versus the Lantus. Dr. Sean Kane 14:10 Then how many units is in one pen of the Lantus Solo Star? That will be 300 so they've really moved two things on you. They made it so each pen has more insulin, but they gave you fewer pens. But like you said, the sum total is a little bit lower, which that's actually a really intelligent marketing move. So we do see maybe a little bit of a price bump for the drug company, a little bit more expensive for the patient. Clearly, patients that are on massive amounts of Glargine every day, this would be a great option for them if they're finding that they get a lot of discomfort from a large volume injection. Dr. Patel, do you see this more as a patent extender for the drug company, or is this like a true unmet need for certain diabetic patients? Or where do you see this drug in five years? Speaker 2 14:51 You know, currently with the data and the information that we have from clinical use, you know, so called post marketing observation. I feel currently this place is more of a fill in the shoes patent extender, with this changed pharmacokinetic and dynamic profile, we might be able to see its niche develop in in certain patients, obviously you mentioned those who are in high volume of basal insulin, but also in those patients where there is the veering off effect at the end of insulin Lantus dose, or, you know, just before the Lantus is due, because Lantus is kind of, they say, manufacturer says the half life is anywhere from, or duration of actions anywhere from 20 to 24 hours. So sometimes patients, by the end of that 24 hours, they have hyperglycemic episodes. So with this Toujeo, going about 32 hours and keeping the administration still once daily, we're thinking that you're giving that continual coverage of the medications. So I feel that is the biggest difference, if Toujeo brings anything to the plate. But other than that, I think it pretty much filled in shoes for Lantus and of Dr. Sean Kane 16:04 course, to your point, of those patients that have that wearing off effect, if only a portion of the patients in the clinical trials had that effect, where they only lasted 20 hours with glargine, we may not have seen that in the clinical trials, where Toujeo didn't really perform, you know, much better than Lantus did. So it could be that in that particular patient population Toujeo does have better efficacy. We just weren't able to kind of see that in a clinical trial of a bunch of different patients that have a bunch of different half lives of Lantus. Speaker 2 16:34 That's correct, because insulin gives very different dynamics in different patient populations. Cool. Dr. Sean Kane 16:42 So moving on to the next agent. It's a Humalog u2 100. This is basically a more concentrated form of what has already been on the market. Humalog u1 100, right? Speaker 2 16:51 That is correct, and it was approved in May 2015 so again, the concept here is the same. You're trying to utilize less volume. Speaker 3 16:59 And my understanding is that it's this one, though, is not to be used in pumps or in IV formulations. Speaker 2 17:05 Currently they are advising against because the pumps that are out in the market are calibrated to use only the u1 100 type insulins. Dr. Sean Kane 17:14 Yes, in terms of kinetics for Humalog u2 100, I would assume it has to be very similar to u1 100. You know, rapid acting insulin lispro in terms of onset of effect and how long it lasts and things like that. Speaker 2 17:28 It's very similar to u1 100. So if you look at the time for maximal glucose lowering, so T max, basically it's 2.8 hours with u1 100 versus 2.4 hours with the the u2 100 and the glucose infusion rate is where you see the glucose lowering effect. It's 534 milligrams per minute with u2 100, versus 559 with u1 100. So they're pretty much similarly functioning here. The idea is just basically less volume, and if you're converting from any other rapid acting insulin. This will be a one to one conversion, all right? Speaker 3 18:04 And I know we talked, we just talked about with with Glargine that we were looking they're going straight to a pen and completely avoiding the vials. Is that the case here as well? Correct? Speaker 2 18:14 No vials available. Only pen formulation is available. So I think this is a good thing, Dr. Sean Kane 18:19 yeah, so that's a good thing, like you said, that less room for error in terms of dosing and things like that. Speaker 2 18:24 Here the pens are three ml, and each contains 200 units per ml, so you get about 600 units per pen. Dr. Sean Kane 18:32 So in terms of cost, what are we seeing with the Humalog u2 100 versus Humalog u1 100? Speaker 3 18:38 So it looks like what we're talking about is double the cost. Essentially, $206 versus $103 we're looking at 1200 units of the u2 100 at $206 versus 1500s of you 100 for about $103 Speaker 2 18:54 so basically, when you try to get you 200 you'll get one box that has two pens, and so you get total of six ml versus the Humalog, it's a box of five pens. You get 15 ml. Dr. Sean Kane 19:05 So what is the patient population that would want to spend double the amount of money to get more concentrated version of insulin, but fewer units Unknown Speaker 19:13 overall per package? Speaker 2 19:14 Well, that is definitely a good question most of the times. You know, in my clinical practice, I've seen patients with mealtime insulins. They're not utilizing whole lot of dose Now, you might have patients who are on three times a day, fixed pre meal insulin and then some sliding scale, you know, depending on how their glucose is controlled. So if they're utilizing a whole lot of Humalog throughout the day, then maybe I'm thinking this concentrated form will work better for them. Speaker 3 19:46 All right, so I believe that there's another agent that recently came on the market, and this one's brand, brand, brand, spanking new. Speaker 2 19:52 Is that correct? That is correct. Actually just got approved last Friday. All right, staying on the cutting edge here, folks. And so this one. Is a different type of insulin altogether. So we have basal insulin, bolus insulin, and then in basal we have the intermediate acting and long acting, and then bolus, we have the short acting and rapid acting. Degludec actually is an ultra long acting insulin, and it was just approved three days ago. They actually applied through FDA in 2013 and it was rejected because they did not have cardiovascular outcome studies done. And we discussed during past few podcasts involving diabetes medication that now FDA requires a trial that completely shows cardiovascular no cardiovascular harm, and they're bringing this medicine market. So it was originally approved in Europe with the brand name of Tresiba. And finally, the Novo Nordisk got FDA approval. So you'll it hasn't been it has not become available in the market for customer use yet, but has been approved. Dr. Sean Kane 20:59 So then, just to clarify, degludec is the generic so it's insulin degludec with Tresiba is the brand name. Speaker 2 21:06 That is correct. So Tresiba is the brand name and degludec is the generic form of insulin. And as we covered, you'll notice there is another formulation of degludec also approved. Dr. Sean Kane 21:19 I'm going to go out on a limb here, and I don't treat a lot of diabetes, but I would assume that an ultra long acting insulin is going to be a basal insulin that you inject once per day that controls your basal glycemic control Absolutely. Speaker 2 21:33 And that's that's what we're looking at. And the word Ultra comes from ultra long duration of action. So we cover Toujeo and say the duration of action sometimes can be seen 3032, hours. Guess what? With this one, you got greater than 42 hours of duration. So this one is a true basal type of insulin. Speaker 3 21:55 And so if that's the case, that this one's very long acting, does it have a slower time to start acting? Are we talking? Maybe it won't kick in for a few hours. Speaker 2 22:03 Actually, they're saying somewhere between 60 to 90 minutes. So anywhere between hour, hour and a half is the onset of action. So it's a little bit quicker than Toujeo, if you can remember what we discussed in there, you essentially do not see any peak. So if you were to look up some of the graphs, which we cannot show here, you would see that Toujeo still has that little onset of action, you know, going up, and then it kind of puddles out. If you see degludec, you inject it, and it's that gives you that nice straight line type of profile. Dr. Sean Kane 22:35 So like Lantus, and like some of our other long acting insulins, is this also a clear product, correct? Speaker 2 22:41 And that being said like we cannot mix Lantus with any other insulin, this recommendation is the same. It should not be mixed with other insulin at this point. And when we talk about mixing with other insulin, we're talking about mixing physically in one chamber, ONE syringe. A lot of students get confused when I tell them, Oh, you can't mix the insulin. So they think that I cannot have a patient on a cloudy and a clear insulin obviously given at a different time different area of the body. That's not the case when we talk about mixing the insulin, we're talking about physically putting two Dr. Sean Kane 23:16 together in terms of mixing. Did the manufacturer provide vials for this, or is this only a pen? Speaker 2 23:22 Once again, like I said, the formulation still not out yet. They're still going to do their big launch, but we have heard that they're going to introduce flex touch pen technology. That's the new one that Novo has developed where the dialer doesn't come all the way out, so your thumb doesn't have to extend if you're taking longer doses, it twists inside the pen device Dr. Sean Kane 23:44 itself, and that would be in contrast to, like the Solo Star that does come out, that is correct. Speaker 3 23:49 All right. Then I wonder, then, is it different in terms of kind of the time it takes to almost tick down as you squeeze the button on it? Will that be a little bit different and kind of that tactile clicking down as you go through the uses Unknown Speaker 24:00 that is correct, yep, yep. Dr. Sean Kane 24:02 So then at this point, as far as we know, the adverse adverse effects and the efficacy and the warnings, all of those things are going to be very similar to what we see with our other long acting instance, right? Speaker 2 24:12 That is correct. So far, the adverse reactions and warnings are pretty much similar, including hypoglycemia injection site issues such as fat distribution changes. Speaker 3 24:23 I know we talked about accumulation a little bit ago. I'd be curious to know again, about about it with with this drug. I wonder if they have done, or if they're considering doing some sort of an every other day kind of dosing, just to see, see what it does. And that's that say, Speaker 2 24:36 Yeah, further studies on pkpd should be reviewed. Dr. Sean Kane 24:41 So given that the kinetic profile is a lot longer than Lantus, what are we seeing in terms of recommendations for Tresiba, if you're going to go from Lantus to Tresiba, currently, Speaker 2 24:51 the manufacturer is recommending one to one conversion, although I'm a little skeptical because of the longer duration of action compared. Hearing the two. But currently, for your following manufacturer's recommendation, it will be once a day dosing. Dr. Sean Kane 25:06 And I can tell you that, you know, especially once this actually makes it to the market where a patient can buy it in a pharmacy. I'd really be interested to see longer term studies, you know, phase four studies, in terms of hypoglycemic rates and efficacy studies, given that, kinetically, it's very, very different than Lantus, and you'd expect, as an example, more hypoglycemia in patients that don't know that they will miss a couple meals the following day. But normally it wouldn't be a big deal with Lantus, but with this one, because it's still lasting, seeing some hypoglycemia with that. Speaker 3 25:37 I know if you look in the European guidelines, then the nice guidelines do have some some data with statistically significant reductions in the number of hypoglycemic events when comparing it with glargine and a similar tolerability. And those are in some 52 weeks of studies, right? Speaker 2 25:52 And I think if you look at the the cases you know we talk about glargine being so safe in regards to the nocturnal hypoglycemia, they're saying that degludec actually has even lower incidences of nocturnal hypoglycemia compared to glargine Dr. Sean Kane 26:06 Dr. Patel. Just to end on this point, would you mind talking more about that for the listeners, about hypoglycemia at night time with long active insulins? Speaker 2 26:16 So you know, we, for the longest time, to use as a basal insulin. We had the NPH insulin, and one of the biggest thing with NPH was that it was causing patients to have nocturnal hypoglycemia. Basically, it's the hypoglycemic episode that occurs in the middle of the night. Hypoglycemia in general, is not good to have, but when it occurs in the middle of the night, sometimes patients do not feel the symptoms enough to wake up and realize that their sugars are low. And this could be particularly very dangerous, because if they don't realize the initial onset of hypoglycemia, their sugars didn't just keep dropping, and they can easily convert into coma. And so we needed an insulin product that would not give us nocturnal hypoglycemia. And so when glargine came out on the market, you know, it was very apparent and easy for clinicians to recognize to use a safer glargine. And now we're talking about degludec, which has even a little bit lesser nocturnal hypoglycemia episode. And was it Dr. Sean Kane 27:16 something about the kinetic profile of NPH that gave it more nocturnal hypoglycemia, or was it something else that we don't understand about Speaker 2 27:23 the drug? So if you're looking at the graph comparing the pharmacokinetic and dynamic of glargine and NPH, glargine has a little peak, but then it's relatively very flat profile. If you look at NPH, it lasts for about 10 to 14 hours. There is an apparent peak, and that peak usually occurs around six to eight hours. If you think about how NPH is given it's usually twice a day. And so, you know, people were getting that lowering, low hypoglycemic episodes when NPH was working at its peak. And so somebody was taking 10 units of NPH at bedtime, let's say around nine o'clock. Think about that. Four o'clock, three o'clock in the morning. It's about that six hour peak time. That's where they were developing the low sugar episodes. Dr. Sean Kane 28:11 So you're saying that for these basal lung cracking insulins, as you would probably hypothesize. Now, it's advantageous to really have as little peak as possible to avoid some of these Unknown Speaker 28:20 issues. That's absolutely correct. And just Speaker 3 28:23 to circle back to what we were talking about, I was able to pull up the data from that European study. It was a one year study, and they looked at glargine versus degludec. And actually what interesting when we talk about it having a lower risk of the nighttime hypoglycemia and overall hypoglycemia, they actually started them out at 10 units per individual. That was the starting dose of both agents, and at the end of the study, the average doses were point five, nine units per kilogram for degludec, and point six, zero units per kilogram for glargine. So the whole time that it had that lower risk of those side effects, they were looking essentially still at that one to one dosing, and that was over a one year period. So perhaps that isn't it, or that we'll still see that one to one as people continue on the medication. Dr. Sean Kane 29:06 So just to review the three agents that we talked about today. The first was Toujeo, which is insulin glargine, which is a more concentrated version of an existing product called Lantus that is already on the market right. Speaker 3 29:17 And the second medication we talked about was the Humalog u2 100, which again, is a more concentrated form of the same medication. There the same short acting and rapid acting insulin. Speaker 2 29:29 And the third one we talked about is a whole other class of insulin called ultra long acting insulin. And generic name is degludec. It's available in u1 100 and u2 100. The brand name is Tresiba. And although we would like to talk to you about all the different new insulins that are out, quickly mentioning that Tresiba combination a combination of degludec and aspart is also out with the brand name of Ryzodeg, it's a 7030 combination, and so it's also approved, along with Tresiba. Kinetic profile is a little bit different. It's a combination insulin and usually combination insulins are given twice a day, but this one will be given once a day with whatever meal they would choose. I probably would like to give it with the biggest meal of the day, considering it's given once a day, and onset of action is five to 15 minutes, and the peak occurs somewhere around 30 to 60 minutes. So the peak and the onset is more if you can think about aspart the way it works, it's kind of reflecting that Dr. Sean Kane 30:29 very interesting. So for the listeners who haven't visited us already, we're at HelixTalk.com we love five star reviews and iTunes because it helps other listeners discover the podcast. If you have any episode suggestions, you can email us at HelixTalk.com. We have our contact information there with that. I'm Dr. Kane, I'm Dr. Schuman, and I'm Dr. Patel. Study hard, everyone. Narrator - Dr. Abel 30:51 Thank you for listening to this episode of HelixTalk. This is an educational production copyright Rosalind Franklin University of Medicine and Science. For more information about the show, please visit us at HelixTalk.com you.