March 13, 2019 Diabetes medications and types of insulin

[00:00:05] Hi everybody welcome to the webinar. We're just going to get started now. So today we have a link to share with us. And so just before we start I'm going to let you know that on the bottom right hand corner we have the chat box for everybody. I don't regulate that or I don't facilitate the conversation from there. Feel free to chat with one another. If you do have a question, you can type it into the bottom left hand corner in the Q and A pod, and we will address those questions at the end. So without further ado we'll get started. We are generously supported by Janssen and One Touch, and so I'm going to give it over Elaine Cook who is a pharmacist and a CDE, she's a certified diabetes educator. And today she'll talk to us about diabetes medication. So Elaine please take it away.

[00:00:57] Hello everyone. Just before I do it I just going to mention to Sharon that someone can't see the visual apparently in the chat box here. So today. Yes our topic is diabetes medications and what we're going to do is just talk a little bit about the difference between type 1 and type 2 diabetes and what causes the high blood sugar when you have type 2 diabetes. And then we're going to go through the medications, talk about the oral medications injectable and insulin, and just a little bit about hypoglycemia.

[00:01:33] Just looking at my little screen here. So. As all of you probably know if you have type 1 diabetes the body has destroyed the cells that make you able to produce insulin and that type 1 has to be treated with insulin. And type 2 diabetes it can be either a lack of insulin or a lack of the action of insulin. That's called insulin resistance. And of course you all know I hope that type 2 diabetes is a progressive disease. By the time you get diagnosed with type 2 diabetes the ability of your beta cells in your pancreas to produce insulin is already only at 50 percent and that loss continues. So realistically eventually almost all people with type 2 diabetes will require insulin even if it's just one shot a day to control their blood sugar. And there's a lot of fear about insulin. But I think you all just need to think of it is it just another choice of therapies. And you know to treat your diabetes you have to control your lifestyle so you have to look at your portion control the types of foods you're eating, looking at your weight, getting regular physical activity, and stress is very important. So you need to find ways to deal with stress as well. And of course I'm a pharmacist, so when you're prescribed medication it's really important that you take it. And if you're not taking it it's really important to let your doctor know that you're not taking it. So he doesn't think well they're on that and that's not working so I'm going to try something different. So where does the high blood sugar of type 2 diabetes comes from. A lot of times the very first thing that changes is that the liver starts to release more and more glucose because glycogen, which is from where the glucose comes, is stored in the liver and that increases your blood sugar. And primarily it's your fasting blood sugar which is your morning blood sugar that starts to increase at that time and then the pancreas, it eventually will get so there's decreased amounts of insulin secreted. And when you have less insulin, the insulin takes the sugar out of your blood and puts it in your muscles. So if you have less insulin, more sugar stays in your blood. And again it can increase your blood sugar. And there is another hormone that's released by your pancreas by different cells and it's called glucagon. And glucagon actually lets your body release more sugar into your bloodstream. And even though you lose the insulin you do not lose the glucagon. So the glucagon adds more and more sugar into your bloodstream. And we have this insulin resistance so that the insulin would take sugar into your muscles and your fat cells for energy and for storage. But because the insulin can't work it's like coming up against a brick wall more sugar stays in the blood. Increasing your blood sugar. The amount of carbohydrate you eat often increases because of this hormone GLP one which is a naturally occurring hormone that all of us have that helps regulate your appetite, it helps regulate the insulin secretion, and it helps regulate the amount of glucagon that's released as well. So all of those things combined one or the other or gradually maybe more than one of them cause that increase in blood sugar. And the reason I've done this is because I wanted you to know where do medications work. Often people tell me oh I have to take another medication so I've been bad. No it's physiological changes that I've just explained. And medications work in different areas so sometimes you have to use multiple medications to get your blood sugar under control. So the drug called Metformin, and also insulin and the other two that are down there, they work by decreasing the amount of sugar that is a lot of dietitians call it leaky liver. So the amount of sugar that's leaking out of your liver and that's primarily where metformin works and then we have, that causes lower blood sugar, and then we have medications that help your pancreas release more insulin. And those are the things that Glyburide, Glycazide, Gilmepiride and I'm going to talk about these in a little bit while a little while as well. The Replaginide, Insluin, GLP one drugs that are injectable and the DPP 4 inhibitors. So don't worry about the names because they're going to come up in a little while. But what happens then is it increases the amount of insulin and it suppresses the glucagon in different drugs which we'll get into later. So that works to lower your blood sugar right. And then we have drugs that are called Thiazolidinediones, Rosiglitazone, Avandia, Pioglitazone, Actos, they're primarily action is to decrease that insulin resistance and let the insulin take the sugar into your fat and muscle cells. Insulin does that as well. And Metformin to a very small degree does that. And then we're going to have medications, oh by the way it lowers your blood sugar, so then we have medications that work in the intestinal system in your gut. So we have Acarbose, which slows the absorption, and we have drugs that affect that hormone I talked about the GLP-1 whether it be a GLP-1 or a DPP-4. And of course what happens then is it's going to help to lower your blood sugar, so hopefully that kind of overview just gives you an idea of why you need multiple types of medications. And please note that insulin tends to do all of those things. So metformin, it's primary action is in the liver. As I said it slows that release of the sugar from the liver and secondary effect to a minor degree, it decreases insulin resistance and it's taken with food. Any of you that have already taken metformin knows that it can cause some side effects so if you take it with a small dose and gradually increase the dose those side effects are diminished and the maximum amount of that is 2550 milligrams per day. But about fifteen hundred milligrams so three tablets a day of the standard tablet is about 75 percent of the action of Metformin. Those possible side effects, the nausea, vomiting diarrhea, those are probably the ones that if you're going to experience you're going to experience that one the most. Some people get headache a little bit of agitation sweating, weight loss, some people think it's because it makes you nauseous, but there has been studies that show that it can cause a little bit of weight loss. And if you take more than 15 hundred milligrams for more than five years there has been some evidence that it might decrease vitamin b12 levels but there's not enough information out there to tell you to supplement, it won't hurt you, but you can do it. It does not cause hypoglycemia. This is a big misconception. I've had a lot of people tell me oh well you know I take an extra metformin if my blood sugar is really high. Well it's not going to drop your blood sugar from where it is going to prevent it from going higher by preventing that sugar coming in from the liver. So metformin by itself does not cause you to have low blood sugars. Otherwise known as hypoglycemia, or a blood sugar of less than 4. What it does and it takes about two weeks for it to work, is it has a big effect on what your morning blood sugar is. That's that fasting blood sugar. And it can decrease that from about three point three to three point nine millimoles per liter. And usually it's not right away. It tends to take about two weeks for those effects to be noticed. And a lot of oral medications lower your A1C in this 1 percent range. So A1C the test that you go for every three months, which is a percent number that reflects what your average blood sugar has been for the previous three months. In the case of metformin it will lower your A1C approximately one to one and a half percent. And then we have the TZD. These are the drugs that have had a lot of steady and bad press. And in Canada, you'll have to have a contract with your doctor to start this medication to know that you've been made aware of any possible side effects. And that's Avandia or Actos. What it does is it decreases that insulin resistance, so it lets insulin carry the sugar into the cells. And one of the things they noticed about this medication is that it tended to keep that effect for a longer time than a lot of oral drugs. And its secondary effect is that it effects that sugar release from the liver as well. And again by itself, it cannot make you have a low blood sugar because taking it does not drop your blood sugar down really quick. Doesn't matter if you take it with or without food. One of the challenges this drug is it could take up to 12 weeks to work and when it was a popular medication a lot of people and it was expensive and it still is, people think well I've taken this thing for two weeks and not much has changed but unfortunately could take up to three months for it to have an effect. The side effects of those that I've listed they're probably the most important that came to light is the fluid retention. Fluid retention is retaining fluid in the body, which led to some heart failure, which is one of the reasons in the studies that were done, that there was a slight increase in the risk of heart attack. But it was always not to be used in anybody who had heart failure. And now it should not be used anyone that has any cardiovascular disease. Occasionally it could have caused an upper respiratory tract infection so that would be like nasal stuffyness etc. There have been some signs of it causing a wrist fracture that's primarily been in women with long term use. But as I said this class of drugs nowadays are very rarely prescribed, although in the states they're starting to use them again. Again its effect is primarily on that fasting, that morning blood sugar and it decrease that by about two point two to three point three millimoles. And it's again affected A1C from about 1 to one and a half percent. So very similar to a lot of these oral drugs. A class of drugs that they call sulfonylureas that effect the pancreas the beta cells. So that's Glyburide, Glycazide, Glimepiride, which isn't used a lot. and What they do is, I used to use an analogy like it's if your pancreas is a sponge, these drugs squeeze the sponge to get the insulin to release into your bloodstream so that it can work. And these medications depending on the form because some of them come as regular tablets and some that come as long acting tablets. Like Gliicazide comes as Dimaicron MR, whereas glyburide is usually wants to twice a day, Diamicron regular tablets can be up to three times a day. Diamicron MR, even if you're taking three or four of them only needs to be taken once a day. It's important when you're taking this medication that you have regular meals because this medication squeezes your pancreas to release that insulin. The side effects, hypoglycemia is quite common in these, especially if you've missed a meal or you've done more exercise. They do tend to cause a little bit of weight gain up to about five pounds. If a person is allergic to sulfa not it's not always a problem but it's a concern. Sometimes the doctor will give a trial of this to see and the glyburide one should not be used in anyone who has kidney failure. The Diamicron, the glimepiride, they're newer agents, and they are more dependent on what your blood sugar is, and I called it glucose dependent on these slides. So whereas glyburide it's like the indiscriminate one of the bunch. It will squeeze your pancreas and release insulin no matter what. The Glicazie, the glimepiride, they pay attention to what your blood sugar is and they release insulin based on what your blood sugar is. So they're less likely to cause that hypoglycemia. And again they decrease your fasting blood sugar your morning blood sugar almost up to 4 millimoles per liter and decrease A1C one to one and a half percent.

[00:15:01] There is another group that worked very similar to those sulfonylureas, the Meglitinides. They also work in the pancreas. So Gluconornm, Starlix, these medications work really quick so they have short term, and it is again dependent on what your blood sugar is, release of insulin. And of course none of these are going to work if you don't have a functioning beta cell. People have been on this type of medication for a very long period of time and their blood sugar is going up, they probably don't have a lot of function left in their beta cells. This almost acts like an oral insulin we'll call it because it acts very rapidly. When you take this medication, you take it only with food and it works very quickly and it has its peak action within about an hour, lasts for up to four. It's usually taken at the mealtime or up to 50 minutes before your meal time and you usually can take up to one to four tablets because it really depends on the size of the meal and how well it's working to control your blood sugar, two hours later. This is a medication that's often used for people that are really irregular eaters, they don't eat at the same time of day whereas with the sulfonylureas, it's more important to have that regular eating with this one because you don't take it if you don't eat right. And it can cause hypoglycemia but much less so than those sulfonylurea drugs, and it can cause weight gain. It reduces your after meal blood sugar so you're two hour after the blood sugar by up to three point three millimoles per liter which is pretty big. And it reduces the A1C 1 percent for the Repaglinide and only a half a percent for Nateglinide. So we don't really see that Starlix use very much at all in Canada.

[00:17:02] So then we have the Alpha-glucosidase Inbihitor and Acarbose. And what it does is it slows the rate of absorption. If you slow down how fast it makes your blood sugar rise it's going to let the insulin that you do have work a little better. It's always taken with the first bite of the meal and the dose should be increased slowly, so they take it with one meal and then they could take it at other meals or they might even increase the dose from 50 to 100 milligrams. Every two to eight weeks is when they increase the dose. This drug has a really big problem with causing gas. It's all abdominal thing. So you know abdominal discomfort, the gas is something that's a real challenge for a lot of people. Someone told me that you have to really want to be alone for this medication and unfortunately taking an antacid or taking some stomach medication does not relieve that abdominal discomfort. It by itself does not cause hypoglycemia but should you be on this medication with any medication that can, it would be very important that you treated that hypoglycemia with dextrose tablets not with orange juice not with honey because those are carbohydrates. Right. And it would slow the rate of absorption. So if you had a low blood sugar, when you're on this medication you have to use dextrose tablets such as Dex4 there is a straight Dex tablet available. It reduces your after meal blood sugar, almost three millimoles per liter and it reduces your A1C from half to 1 percent.

[00:18:48] Then we had therapies that came out about five or six years ago that were called incretin therapies that have their action in the gut. And we have an Incretin hormone that I was saying was naturally produced in your intestines and it is released in response to eating. And the main one there is a couple but the main one is called GLP 1 or glucagon-like peptide 1. And there's lots of different actions of GLP 1 that helps your blood sugar be regulated. And when you have type 2 diabetes you actually have less GLP 1 than someone who doesn't have it. And that's going to be important in a little while. And the challenge with the GLP 1 naturally occurring, it is inactived within about two to eight minutes in everyone by an enzyme called DPP 4. And that happens in every person. So the multiple actions of GLP 1, naturally occurring, to reduce your blood sugar or in fact to maintain your blood glucose if you don't have diabetes, is again depending on what your blood sugar is, it helps release of insulin help stimulate that release of insulin depending on what your blood sugar is it will suppress that glucagon. Glucagon would have come to your rescue and if you don't eat at all all day long glucagon will produce sugar because your body needs sugar to act right. But as I mentioned at the beginning, that glucagon in type 2 is often like on a rampage. So GLP 1 helps suppress that action of glucagon, it slows gastric emptying so it slows the rate of absorption of food and in animals, it has improved beta cell function and increased the beta cell mass. It helps give a person a feeling of fullness to help them realize when it's time to stop eating which is when you lose some of you GLP1, a lot of people with type 2 overeat because they don't have that action to make them realize that they're full. So of the iIncretan therapy's, DPP 4 inhibitors, they're around to slow the action to slow the activation of GLP 1 which I told you was inactivated by an enzyme called DPP 4. So these inhibit the action of that enzyme. So there’s Sitagliptin which is Januvia, Sacagliptin which is Onglyza, Linagliptin which is Trajenta. And these can be used by themselves or they could be used along with metformin. And in fact there is a combination of all of those medications with a different name. Side effects. Most people do not experience any side effects with this class of medications. It is possible that it can cause that stuffy nose but it doesn't have any effect on weight at all. It reduces the after meal blood sugar it's two point seven millimoles per litre and its effect on A1C is almost up to that 1 percent, 0.8 To 1 percent. And then we have injectable therapies. GLP 1 analogues. So Byeta, tt's injected twice a day five to 10 micrograms, it's given with meals. That's important. And then there's Victoza, which is injected once a day in the morning. This can be added on to metformin or on to someone who's taking metormin and a sulfonylurea as well. And I have seen a lot of people who are on it just by themselves now because it tends to be looking at multiple effects that happen in the body that cause that type 2 diabetes. The analogues are not broken down by the DPP 4 enzymes. Though it's not affected by bad side effects nausea, ore so with the Byeta, about 36 percent of people get nauseous with Byeta. With the Liraglutide, they start off being nauseous but usually after about two to three weeks that nausea diminishes. Anybody who's taking Byeta or the Victoza and still feeling nauseous should just eat smaller more frequent meals. As well as the nausea. These medications can cause vomiting, diarrhea, it can cause hypoglycemia if it's used with a drug that does like the sulfonylurea drugs. By itself, limited amount of hypoglycemia. Weight loss averages almost 2 kilograms. But there have been people that report significant amounts of weight loss and maintain weight loss with these medications. There have been stories of people losing 40 pounds or more. But the studies that were done originally with this drug before it was released, on average it was just that one point nine kg, which is just under five pounds. It reduces your after meal blood sugar by 2.7 to 4.5 millimoles per liter. So that's the biggest one that we've talked about so far. And A1C can be anywhere from half a percent to 1.3 percent. And I have actually seen people that have had a 2 percent reduction in their A1C. So then we have a new class of drugs that has come out. Actually, it was released in Canada somewhere about February. And those drugs work on the kidney. I thought you should know what happens normally in the kidneys. So the kidneys play a really important job in maintaining your blood sugar control because normally in the kidney, it filters about one hundred and eighty grams of glucose every single day. But because it wants to keep that, it virtually reabsorbs all of that so you get to keep that into your circulation because we need glucose for energy etc. It's our main fuel. So there are two sort of proteins that are in the kidneys and they're called SGLT2 and SGLT1. The SGLT2, it reabsorbs about 90 percent of glucose. And the other one about 10 percent. So that essentially no glucose gets excreted. Now this is in someone without diabetes. When you have type 2 diabetes, number one year ago we used to test for diabetes with urine test it because glucose was spilling over because it was exceeding the amount that the kidneys could work on. But in type 2 after a while your body actually reabsorbs more and more glucose. So again it adds to the blood sugar. So this SGLT2 stands for sodium glucose co-transporter 2 and it's the inhibitors, so inhibiting the action of that is going to let your body release more sugar. Because that SGLT2 helped reabsorb 90 percent of it. Right. The one that we have in Canada is Invokana. It's taken once a day before the first meal of the day. And what it does is it helps you pee out about 300 calories of glucose per day. It increases the urine though, it can be used alone or it could be used in combination with metformin. It could be used in combination with a sulfonylurea drug. It can also be used in combination with insulin. It's not used to anybody whose renal function has decreased. And your doctor would know this number so anyone who had an estimated GFR, globular filtration rate of less than forty five these people would not use this medication. Canagliflozin, there is a number of side effects. Of course because you're helping pee out more sugar, you're going to pee more, increase urination. And it can also cause dehydration, which can cause that dizziness that constipation and the thirst. So with the dehydration you're at higher risk of getting dehydrated if you're over 65, if you take blood pressure medications, and especially diuretics drugs like or if you're on a low sodium diet, or again if you have kidney problems you're at greater risk of having that dehydration. It has been known to cause urinary tract infections because it's making a lot of sugar in the urine as well as causing genital yeast infection. They have found though that they don't tend to be ongoing. Basically you tend to get those infections at the start of the therapy but after a while it doesn't happen. Because it can keep more potassium in your body as well, there can be an increase in the blood potassium, so some kidney problems; this will be a big problem for them. There is an increase of low blood sugar, if it's used with a drug that can cause low blood sugar. It lowers the A1C up to 3 percent. This is a pretty large number and a pretty awesome result and I think we're going to see a lot more people on this medication. And there are more of this medication coming by the way, in the states they already have a couple of different ones.

[00:28:58] Let's talk a little bit about insulin. So someone who does not have diabetes then this light blue line represents the insulin that's released normally in a body. B is breakfast, L is lunch, D is dinner, HS is bedtime. So your body has a pretty rapid amount of insulin to release to cover a meal when you eat and then it tapers off and goes down. So. You're looking for an insulin. If the insulin could mimic this normal insulin secretion. Bolus means meal time. Then a bolus insulin that matched that would be a really good choice to look at. And our body has a requirement for what they call basal or I'll call it background insulin that you have to have a little bit of insulin all the time for your body's functions, for everything to work correctly. So again if you could get an insulin that kind of mimics that basal amount that your body needs, then that would be an ideal insulin. So just as an example here, this is the normal, doesn't have diabetes that was just like I showed you. And that keeps your blood sugar pretty much controlled. This is an American slide that I borrowed. So that's why the numbers on this side are milligrams per deciliter and not millimoles per liter. Now somebody has type 2 diabetes. This is just naturally what happens in the course of developing Type 2, is it you get a very blunted and delayed release of insulin. This is again why your blood sugar can be so much higher, because it's not controlling your blood sugar when you're mealtime glucose level goes up.

[00:30:54] So these are all the different types of insulin that are currently available in Canada. And you will find many different charts especially on the Internet that have slightly different numbers. These numbers they come from the Canadian Diabetes Association's guidelines for the treatment and prevention of diabetes. But there is insulin that act really quickly. They're called rapid acting insulin analogs. So they're man made insulin. Humalog, Novarapid, Apidra. And they really work within about 10 to 15 minutes, and their action 1 hour peak usually one to one and a half hours, and they'll have some residual effect for up to three to five hours. We have the short acting insulin which is known as regular or R. This is a human insulin. In Canada, we have humans we don't have beef and pork anymore, which I'm sure you all know. But I've been around long enough that there was beef and pork insulin. It takes about 30 to 60 Minutes for short acting insulin to work. That's why it's really important if you're taking anything that has an R, regular insulin in it that you take at least 30 minutes before a meal. It can take two to three hours for its peak action to occur, and it can last up to six and a half hours. And there's an intermediate acting insulin which is known as NPH or N insulin. It takes one to three hours to work and in some people up to four hours. The peak action of that insulin is over five to eight, and then has an action lasting up to 18 hours. There are pre mixed human insulin’s and these numbers represent how much R insulin and how much N insulin. So 30/70 insulin would have 30 percent of regular and 70 percent of N. And then there's a 40/60 and a 50/50. They start to work it because they're pre mixed they're going to have the R action in 30 to 45 minutes for the meal, and their peak action is four to almost nine hours and the duration is 10 to 16 hours. Again this was if you're taking anything that has an R in it and you were taking it for your meal time you need to take it at least 30 minutes before a meal. You have biphasic insulin which a lot of charts will call it mixed analogue insulin’s, but in fact it's not a mix of anything. It is just a portion of the rapid acting insulin, has protamine added to it so it has a longer action. So it has some immediate action and has some longer actions. I'm going to show you some graphs of these and a little bit. So Humalog mixed twenty five, so twenty five percent of it is going to work right away. Seventy five percent, a little bit later. It also comes in a mixed 50. That's usually for a bigger eater. So it has 50 percent of it working right away and 50 percent of it having a long action. And we have long acting insulin analogues, a lot of people are familiar with the name Lantus which is Glargine, which takes about 90 minutes to work and it's basically a flatline insulin there is no peak it's really the closest to mimic that basal insulin I showed you a minute ago. And its action last around 24 hours in most people. The other long acting analogue is Levemir, it takes about 90 minutes to work. It does have a slight peak doesn't go up really high. It has a little slight peak and its duration of action can be very dependent upon its dose and the person. So they say 16 to 24 hours see a lot more people in this insulin on it twice a day. But both Lantus and Glargine I have seen twice a day. So just as a graphic example of how fast they work, so bolus are meal time insulin. This would be the fast acting, the rapid acting. This would be the R insulin. So just looking at the difference between these. The fact that the R insulin takes longer to work and stays around longer, it's not going to ideally control that post meal blood sugar and because of its action, longer it's probably going to cause more chance of a low blood sugar. Then we have the basal insulin, which is that background insulin. So we have the intermediate acting NPH. Again its action is 12 to 20 hours. They may be slightly different numbers in the chart because again I've borrowed this slide from another presentation. The long acting insulin analogues, such as the Detemir, in this case is saying its action is six to twenty three hours, again dependent on dose. And it does have that slight little peak there and then we have the Glargine or Lantus insulin and it again takes about 90 minutes to start working but it's pretty much a flat line insulin and again probably mimics normal insulin secretion much better. So when you're using insulin in type 2 diabetes. When do they usually start it? As I said it's just another choice of therapy. When a person is taking oral medication or other injectable medications and their A1C is still elevated, they can't get it completely controlled, usually an insulin is added and in type 2 diabetes often just at bedtime to start with. So that basal background insulin, once a day could be at most people bed time. NPH would be like twice a day, breakfast and supper. I have seen both Lantus and Levemir largely used in the morning instead of at night often so that people will remember it more. So it's once a day, you don't stop taking your other medications. And quite often just that one insulin, so that's going to get your background amount of insulin done, looks after controlling your blood sugar for a very long time. And some people may never go past this insulin. The idea with this insulin is to start with a low dose slowly titrate it up, so it's like 10 units at bedtime and the person injects one extra unit every day until their morning blood sugar is less than seven or whatever target your doctor decides on. So the long acting the Glargine, they do mimic that natural insulin release much better and have a much lower risk of hypoglycemia. Whereas NPH can cause hypoglycemia a lot more frequently. So this is just showing you the green line there is the NPH. When I drew this I couldn't get too big of a peek so it can cause low blood sugar Between that, especially that 4AM period of time there, if it's once a day at bedtime. And then the purple here or the red is the Lantus. So pretty flat. And then the Detemir has just that slight little peak to it. So just as a representation that white line would be how your blood sugars would be going up. So often if you've been on that Lantus at bed time and your morning blood sugar is great but you're A1C is still high, they're probably going to add a bolus or a mealtime insulin once a day. Right. So usually it's a rapid acting because that's going to be mimicking the natural insulin better at breakfast or they'll say you can pick the meal that has the highest change in blood sugar from before to after but breakfast is quite frequently used because your body naturally has a bigger increase of blood sugar in the morning. And again quite often just those two times a day is enough to control a person's blood sugar for a very long time. The rapid acting insulin it would be to use five to 15 minutes before a meal, Humalog, Novarapid. And you would check your fasting blood sugar and you would check your blood sugar two hours after a meal, aiming to get to that eight to 10. Or your doctor might say we'll just check your fasting blood sugar before you take that insulin and before the next meal and to see where it's at, at that time. Just an example of long acting insulin, which would be used at the Glargine or Detemir lines here, with just adding one meal. So the orange is representing the rapid acting insulin.

[00:39:58] Human insulin, which is the R and the N insulin. It does not mimic normal insulin physiology. So they have a much greater chance of the low blood sugar. Again R-regular Toronto injected at least 30 minutes before a meal or if you're taking a 30/70, 40/60, 50/50, again you'll improve your blood sugar greatly if you're on that type of insulin and you take injected at least 30 minutes before a meal. N-NPH insulin, the cloudy insulin, is very important it's re suspended, never shaken before use it because NPH has a great variability from day to day. So just rock it and roll it back and forth 10 times each. Don't ever shake it. The pre-mixed such as the Humalin 30/70, the Novalin 30/70. That 30 percent are that 30/70 percent, and those are probably the most common ones you see. This would be an example of using a combination the 30/70 insulin’s. You can see that there's lots of spaces where there's blue underneath those lines and those make you much greater chance of having high or low blood sugar and also not controlling the meal increase in blood sugar. So there is also an analogue biphasic insulin which again closer to the normal insulin action. Needs to be mixed by that rocking and rolling 10 times. And because it has analogue insulin in it it can just be injected five to 50 minutes before or even right after the meal. This would be an example of it. This one here is a Novo-mixed 30 or like the Humalog mix 25. And sometimes this is sufficient. It looks like it's missing the lunch time sometimes just taking a little bit at lunch, if that's a big problem, will be good for this insulin.

[00:41:49] So then basal bolus therapy. This is definitely done with analogue insulin. The long acting and the rapid acting insulin’s. Because you've got the background with the long acting and then the rapid acting is going to look after those meals and that's what happens naturally. This isn't for everyone but this is certainly what a type 2 patient is often doing. So this is just an example, here's the background amount. And then we add in rapid for breakfast, rapid for lunch and rapid for dinner. And you can see that's the closest to normal insulin release. So for instance therapy the side effects: low blood sugar is the premium reason that people have a scare about insulin but it's something that can be managed. So low blood sugar is less than 4 millimoles per litre and it's most often caused because people miss a meal or have more physical activity than planned or inject their insulin in a higher amount than they should. So preventing it is knowing those action times that I've talked about, following meal plans, always having extra carbohydrate around for physical activity, and always carry treatment for hypoglycemia with you at all times. And if you're going to do exercise monitor before and during exercise or long driving. And weight gain prevention, it is a common side effect with insulin but healthy meal plans and exercise and talking to a dietitian can really help you with that. So when you're using insulin, almost all insulin’s last for 28 days at room temperature. So when you're using it you want to use it at room temperature. You do not want to put it back in the fridge. It doesn't extend its time and cold insulin hurts. Levemir lasts forty two days. Anything that's cloudy again re suspended, by the rocking and rolling 10 times and never shake it. Always rotate your injection site. You want to pick an area about the size of a postcard above the belly button to one side, onto the other side, below the belly button one side or the other and rotate those sites weekly. So for one week you use a postcard sized area for every injection. Then you rotate so you're not using that site for three more weeks to help the skin heal and always press on your tummy to see if you have any lumps or bumps and avoid those because that could be something called lipohypertrophy. Always use a new needle dull needles hurt and can cause more damage to the skin and lipohypertrophy is overgrowth of the fat in your subcutaneous tissue. And it changes the action of the insulin. You don't ever need to have a needle length longer than six millimeters there is even syringes now that are six millimeters and ten needles six millimeters or less. Four is all you need. Stick it in straight in, count ten seconds before you remove the needle from the skin and don't jab. Just put it there and put it in. Just to finish off quickly here just a little bit about hypoglycemia. So mild to moderate hypoglycemia is defined as a blood sugar of two point eight to four millimoles per liter. Causes like dizziness, confusion, sweating, weakness, hunger, trembling drowsiness, and not everybody experiences the same side effects. If the blood sugar is less than two point eight that's considered a very severe hypoglycemia and it needs a different treatment. So these are all the different symptoms that could happen in hypoglycemia but the symptoms vary from every single person. Stop by your pharmacy and get a chart that gives you all of these: trembling, palpitations, sweating, anxiety, hunger, nausea, some tingling, difficulty thinking or concentrating, some confusion, feeling weak or drowsy or blurry vision or having trouble speaking correctly or getting a headache but everything varies. It's individualized. Always check your blood sugar, if you're having these symptoms check to see if your blood sugar is less than 4 millimoles per liter. If you've had really high blood sugar for a long time and you're starting to get your blood sugar lower you might experience some of these symptoms at higher than four. You can treat it but just don't over treat it just take a little bit of treatment.

[00:46:18] Treatment of hypoglycemia. Always test, as I mentioned some people get hypoglycemic symptoms higher when their blood sugar is starting to go down because their body is not used to that. So if it's two point eight to four millimoles, you want to treat with 15 grams a fast acting carbohydrate such as dextrose tablets. There's one called Dex 4. When your blood sugar is less than four, you take four Dex 4’s, and they have four grams of dextrose each. You could take three quarters of a cup of juice or regular pop three teaspoons of sugar or honey or have six lifesavers. Test your blood sugar 15 minutes later. Retreat if your blood sugar still stays less than four and if your next meal is more than 60 minutes away. You want to have 15 grams of carbohydrate and a protein such as a half a cheese sandwich or slice a whole grain bread with maybe a tablespoon of peanut butter. If the blood sugar is less than two point eight you need more to treat it. You have to take 20 grams of a fast acting carbohydrate such as 5 Dex 4 and one cup of pop regular pop or juice. 4 teaspoons of sugar or honey or eight lifesavers. Again always re-test in 15 minutes to see if your blood sugars come up and if necessary retreat it and if your meal is more than an hour away, have 15 grams of carbohydrate and a protein. If the person is unconscious and you would know if you were on insulin it's only usually occurs in type 1 individuals they would administer another injectable therapy called glucagon. And if you have any questions I'd be happy to answer them.

[00:48:04] Thank you so much Elaine. So thank you everybody for coming. If you have questions please enter into the q and a box on your bottom left hand corner and I will facilitate it and ask it to Elaine. As you are thinking about questions if you have two minutes just fill out the post survey you can just click on the link right there and again will help us shift to better our program. And I guess just as people are thinking about their questions I have one question so Elaine if somebody were to take home a message today what would that be.

[00:48:42] I think it's really important to know what the medications are that you're taking. How they work. And I think you need to know what your doctor has decided or your endocrinologist has decided is your target blood sugar. In general people are to aim for four to seven before a meal and five to ten two hours after. But those could be individualized testing with your with the blood glucose test strips is really important for someone who is on a medication that might cause a low blood sugar. People who just take metformin or that you don't have to test a lot because it doesn't tell you anything. I would tell people if you're going to test, test with a purpose test with some idea in mind but it is important if you have a medication to understand it and to take it.

[00:49:38] So just a couple of comments. People are really enjoying the presentation and they would want to thank you for the presentation. So I do have a question here. Should someone seek advice from an endocrinologist before going to insulin. I am type 2 and have been on metformin for twelve years. Usually your family physician can start you on it. It's not necessary to go to an endocrinologist, and in fact if your doctor is familiar with insulin therapy for he might send you to diabetes education center or to a CDE pharmacist like myself. They have found especially in type 2 diabetes using that long acting insulin analogue like Lantus or Levemir, it's very safe and very easy for a patient to self titrate. It is not necessary to go to an endocrinologist. If you've been on metformin by itself, often they'll try using some kind sulfonylurea first if you're only on metformin.

[00:50:45] Thank you. Another question here: what are the possible side effects of Canagliflozin? Potential side effects are again excess urinary excretion the dehydration is the big concern with that medication there also the urinary tract and the genital yeast infection. Those are probably the most common side effects with that medication.

[00:51:22] Thank you. Thanks for teaching me how to pronounce that. Another question here. Is it OK to take metformin if your kidney function is low. I am also on bolus and basal insulin. Usually with metformin, they usually discontinue that medication if you're in renal failure and they may choose to make that what they call EGFR of less than 30 or renal failure is actually less than 15. I have seen them take people off of metformin when it gets to that kidney level. It really depends on what that kidney function really is. The reason they use metformin along with insulin is they believe it helps keep the dose of insulin to be a little bit less.

[00:52:16] Perfect thank you. Another question here my aunt has diabetes type 2 in her old age passed away at ninety seven years old but never needed to take insulin. Did you relate to your saying that everyone having type 2 diabetes will eventually have to take insulin. There are lots of people that probably can manage it with diet exercise but it's rare. I think if you look at it from. I don't remember my statistics they say I said everybody but they say approximately 60 percent of people with type 2 diabetes will require insulin if that is someone who gets diabetes and it's just almost like a pre diabetes and they're just taking metformin, they may never progress past having diabetes. It is all dependent on what your blood sugar is. But I said that because I want everyone to realize that it could be an eventuality in them because a lot of people think oh no it's the worst thing ever that could happen but I always look at it, if someone has a low estrogen, we give them estrogen, if somebody has low testosterone we give them testosterone. Somebody has low thyroid we give them the thyroid, but if somebody has low insulin it seems to be the last thing we think about. And I think people are put off of it too long you would feel so much better. It's only what's necessary if you can control it the other way. Fine. But if you can't I just want you to take away the idea that insulin is a punishment. Insulin is an excellent treatment.

[00:53:44] Thanks for that insight. So just a reminder for our participants if you like to ask Elaine a question it's easier for me just to keep track of the questions if you entered into the a pod on your bottom left hand corner. The next question is: are there charts to guide us on how much insulin to take for corrective action? There is a formula that your diabetes educator can calculate for that. If what you're talking about is if you're already on insulin, but the blood sugar is high, how much do I take to bring it down. There is a formula based on what your total daily dose is. I don't want to say what it is cause don't you guys playing with it by yourself. But you always have to look at it this way you can titrate it based on what your blood sugar is either for a basal insulin, what you're fasting blood sugar is, for a bolus insulin, either what your next meal time, is or two hours after the meal. If two hours after the meal you're less than ten then you had enough insulin to cover it. If you're fasting blood sugar is less than seven, your basal insulin is covering it. I hope that sort of helped.

[00:54:54] The next question is does Glycon work exactly the same way as metformin? Glycon is metformin. Glycon it's just a brand name.

[00:55:06] The next one is Januvia and metformin is a common combination therapy these days. Is it is common to have sulfonylureas added to this drug regimen. It's not unlikely because you're looking at the Januvia, is that DPP 4 inhibitor. So let's keep in that little GLP 1 along longer. The Metformin is slowing down that release of it from the liver. So if they don't think that Januvia is having enough of an action, they're going to add that sulfonylurea to squeeze your pancreas. You must have some beta cells left. And I I believe in a lot of cases you see people that are on sulfonylureas for a long time and their blood sugars keep going up. But yes it can be used with Januvia and metformin.

[00:56:06] Perfect thank you. So again if you guys have any other questions please them type it into the q and a box on your bottom left hand corner and as you're listening to the Q A session and if you have any if you've two minutes. If you would fill up the post survey we would really would love to hear from you and so we can better our programs. So we have a couple more questions here is taking Lantus insulin twice a day a good way to control high blood sugars before supper? I have a person who takes Lantus at bedtime and in the morning, timing isn't always the best. Not always taken at the same time. Well depending on who you talk to. I've been at diabetes conferences that says there's absolutely no reason you shouldn't just take Lantus all at one time and sometimes it's split. If he's taking more than 50 units at a time, because that's a large amount of insulin. And sometimes rather than having two shots at one time they'll split it for morning and bedtime. The challenges with your high blood sugars before supper really may be related to meal time and Lantus is a background insulin. In theory if you didn't eat all day and you took Lantus your blood sugar essentially stay the same because it's not covering meals. And some people are getting that high blood sugar before supper because it's what they ate and their lunch time, the medicine they take isn't covering the blood sugar raised from lunch. And so that's why they have blood sugar that's high before supper. If you didn't eat all day and your blood sugar in the morning and twice a day Lantus then your fasting would be under seven and you're before supper would be under seven. But because you have meals in between you have to kind of decide what's the challenge. It may in fact be the blood sugar from a meal that is causing is high pre-supper blood sugar.

[00:58:01] Thanks for that explanation. So we have another question here: Januvia indicated for GFR above 50. Trajenta indicated for all renal patients. Do you recommend a change from Januvia to Trajenta with renal patients. Yes that is actually the recommendation for anyone with a decreased renal function, Trajenta has only about 5 percent excreted through their kidneys. So it is a good choice for anyone with decreased renal function.

[00:58:57] Januvia is approved for use with insulin but I have not heard anything regarding Trajenta. Well you know I really I'm not sure of the answer to that question. I will tell you if Januvia is approved the whole class is approved. And I have seen a few people that are just taking a bed time insulin that are using a DPP 4 inhibitor because of course that DPP 4 inhibitor is trying to help with the mealtime as well because it's released in response to your blood sugar. If you were on a mealtime insulin as well, I'm not certain of the total benefit I'm sorry I'm not clear on that answer.

[00:59:45] That's OK. Thanks for trying to answer it. Would taking Lantus and short acting insulin before breakfast help with supper highs? Surprising enough the answer that might be yes. Again it kind of depends on what's causing that high blood sugar at supper. Because what they say is if you can get your fasting blood sugar under control then the rest of the day will be better. And because a lot of times people suffer from something called a dawn phenomenon where you get hormones released in your body that causes your blood sugar to rise naturally in the morning. It is one of the reasons why when they're doing that basal plus one dose of fast acting at meal time that they often will put that meal time at the morning because sometimes that makes the rest of the day fall into place. However if the person's at that point where their blood sugar is always high at different times a day then they're probably a candidate to have a second dose of a meal time insulin.

[01:00:49] So the next question is what is the cost of Canagliflozin, and do you think that government drug plans will pick them up.

[01:00:57] I don't actually recall the cost of Canagliflozin and I don't actually dispense drugs. I am just a counsel so I cannot tell you the exact cost. Government does not cover new medications, at the beginning. We'll hope that it does get coverage eventually. And I'm sorry I can't remember what it is but I believe someone told me it's around the same price as DPP 4 inhibitors. So probably about 70 to 80 dollars a month.

[01:02:01] So we're coming to an end of the presentation. So I'm just going to go through the last couple of slides. But if you do think of another question that you'd like to ask Elaine, again please type it into the Q and A pod and we'll get to it in a little bit. First, a person wants to thank you Elaine for an enlightening session and this person learned a lot and didn't expect to learn so much new information. Oh good. Thank you. So I'm just going to continue with the slides here. And so thanks very much to everyone who attended the webinar today. And for all the wonderful volunteers who coordinated this session we'd like to remind everyone that you will be sent an evaluation survey tomorrow and encourage you to complete it. It should really only take about two minutes and provides us with very valuable information. So this webinar is generously supported by Janssen and One Touch. And if you haven't seen this already it's the diabetes charter. And we'd like to encourage you to sign it. And if you'd like to sign it or for more information you can go to www.mydiabetescharter.ca. And So again the developments and delivery of impactful programs such as our Canadian Diabetes webinar series is made possible through the generous support of our donors. If you enjoyed the webinar and would like to make a donation please visit us at our website at www.diabetes.ca or you can call 1 800 1 800 Banting. Thanks again everybody for coming out today and supporting the webinar. And again if you'd like a copy of the slides or you have additional questions you can email me at infodc@diabetes.ca.