March 23, 2021 Diabetes Treatment Options and Management During the Pandemic

Dr. Lionel Noronha: Let's get started.  It is my pleasure to welcome everyone tonight to the second of three virtual talks on diabetes.  My name is Lionel Noronha.  I'm a family physician in southeast Ontario, and I have a passion for medical education and an interest in diabetes.  I've had the pleasure to participate in, give and help develop many medical education events over the years in diabetes.  One thing I noticed is typically physicians are usually giving talks to other clinicians - mainly other physicians, nurses, diabetic nurse educators, but rarely are physicians directly talking to patients.  So, with the help of an amazing team, we decided to put together these three talks to not only educate but empower and inspire patients to take control of their condition and greatly change their outcomes.  The talks are completely non promotional ,and we've secured some funding for your honoraria for the speakers, which will be forwarded to the nonprofit entity Diabetes Canada, which is committed to serving patients with diabetes. As much as this is a talk, there is an opportunity to interact, and I would ask you to interact via the question and answer link.  Please don't be shy.  All questions are anonymous, and if you ask it there's a good chance that others will benefit from the question and the answer.  I will ask these questions to our speaker primarily at the end, or maybe interject one or two as we go.  Now our first talk was on February 22.  It was by Dr. Alice Cheng, and it was an overview of diabetes and how to approach it, and how to optimize your outcome.  So it was a great success and our talk tonight is focused on treatment options.  Very few disease states in medicine today has seen the growth in research, the landmark studies that have allowed us the exciting powerful new classes and medications that we have available to treat diabetes today.   So, with that in mind, we are privileged to have another incredible speaker tonight, Dr. Robyn Holden is professor and Chair of the division of endocrinology at Queen's University.  She is a consultant in endocrinology at Kingston General and Hotel Dieu hospitals.  She is a medical advisor for the diabetes education and management centre at HDH, and a specialist lead for the southeast Ontario diabetes regional coordination centre.  She has served as a diabetes advisor for the Canadian optimal medication prescribing and utilization service.  And she is extensively published and researched.  I could go on and on, but for the sake of time, I'd like to just finish with this point: she's played a pivotal role on steering committees in the 2003, 2008 and 2013 Canadian Diabetes Association guidelines, and she chaired the 2018 Diabetes Canada guidelines.  So without any further ado, Dr. Holden please take it away.

Dr. Robyn Houlden: Oh thanks - thanks very much.  So welcome everyone.  This is me - I'm here in Kingston.  We had a beautiful, very beautiful, sunny day here and, hopefully, you have the same wherever you are.  I've been a diabetes doctor for 30 years now - that's a long time!  And I’ve been a volunteer for Diabetes Canada for the same amount of time and it's an organization I really like work with they do some very, very meaningful work. 

So here's the agenda for tonight.  I’m going to give you the questions you should ask your healthcare provider about any new diabetes medications.  And I’m going to share with you how healthcare providers, your, your nurse practitioner, your physician how they go about deciding what medications they should be suggesting to you.  And then I’m - just because we're in the middle of a COVID pandemic - just some general hints related to medications and diabetes.

And so I do receive some research support, some speakers honorariums from some pharmaceutical companies.  But, these are just a couple of disclaimers for tonight:

I’m not going to be able to give you individualized advice, so you can type questions in.  But if they're very specific for your condition, you know, without knowing your full medical history, I can't give you super individualized advice.  Although this event has been organized by Diabetes Canada, I have selected the material that's going to be covered, and the opinions I’m expressing are my own.  I’m not being paid, as Dr. Noronha was telling you, by any pharmaceutical company to directly endorse any diabetes medications tonight.

The talk I’m going to be giving tonight is directed for people with type two diabetes, not for type one.  But as Dr. Noronha has maybe mentioned to you, if there's great enthusiasm for offering these types of events in the future, then that could be a topic that you might want to suggest for another night.

When I talk about drugs I’m going to be presenting them Alphabetically.  It's, not because I have a preference for one over another, it's just going to be based on alphabetical order. And that when I talk about drugs, I’m going to show you generic and trade names.  Okay - so what's the generic name?  And what's a brand name?  The brand name is the one that you're going to see in the big lettering, okay?  So for this particular one it’s “Ozempic.”  It's the one that maybe you feel most comfortable using, and maybe the one that used to seeing on ads on American TV.  But when physicians talk about drugs, we often use the generic name.  So, for example, there may be several drugs, um, with the same generic name.  They may be made by different companies, and if they're made by different companies, the companies can have different brand names.  So if you went to buy Aspirin at the drugstore right now, you might find that there's many different names for it but, but, but deep down, it contains aspirin or acetaminophen or Advil, or whatever in it. 

Okay - so that's the difference between brand and generic names.  Okay.  Now, just to hint one thing.  If you really want do to make your health care provider happy, is to always to have an up to date, medical medication list when you would come to visits,  and during COVID, if you're doing phone visits or virtual visits.  Make sure you have that medication next to the phone.  That will really save your prescriber a lot of time.  Many prescribers like it if you brown bag it, rather than having a medication list, you just throw all your medications into a bag and you bring them to appointments.  Now, you're not going to be able to maybe perhaps to do that during COVID, but outside of COVID, brown bagging is a great practice. During COVID, having your medication list and taking it to your appointments is a great idea.

Okay, so what questions you want to ask if your health care provider is talking to you about trying a new medication?  So we're going to go through a variety of different drugs tonight.  And the first question is: how does it work?  Is it a pill or injectable?  So some medications for diabetes are pills, some of them are injectables.  You want to know if it's safe with other health issues, so if you have kidney disease, if you have liver disease, if you have a history of heart failure, if you have surgery coming up.  Is this medication going to be safe under those circumstances?  Are there any additional benefits?  And this is a really big part of the talk because recently it's become clear that some of the medications we use to lower blood glucose and diabetes have other health benefits to them.  So they're not just glucose lowering medications, they have other benefits and that's going to come out clearer in the talk tonight.  You're going to want to ask about when should I take it?  What time of day?  Relationship to food?  Do I take it when I’m sick?  Do I not take it when I’m sick?  You want to know about the common side effects.  You're going to want to know how much it costs.  You want to know if it's covered typically by private health plans, if it's covered by public health plans.  For example if you're over 65.  And then you could ask is there anything else I should know about this medication?

So I put down there, it's always a good idea to have a list of questions at every appointment. I find I’m really happy when my patients come and they've got a list of questions.  I love it when they're written out - that they pass it to me, and they say, “these were the questions I was hoping you you'd answer today.”  So these might be the sorts of questions that you would have ready to ask about your diabetes medications.

So where's the best place to get accurate information about a medication?  So some good sources are from your physician, or many of you will have nurse practitioners.  Your diabetes educator and it could be a nurse, it could be a dietitian.  Your pharmacist is a great source.  The Diabetes Canada website is another awesome site.  Not so good sites - or the Internet.  You can't always trust Internet information. You got to make sure that you're going to a reliable source.  So Diabetes Canada - great reliable place. You might ask your health care provider if there are other reliable sources they would recommend I’m going to show you some during tonight's presentation. Being a little bit careful about family members, your neighbor, co-workers, friends.  Your experience with a medication, just like with a restaurant or a resort, may not be the same as your neighbor’s, your relative’s or your friend’s.  So sometimes people will tell you negative stories, but just remember that their experiences may not be the same as yours.  So you can listen to them, but probably you're going to get more powerful information from the physician, nurse practitioner, diabetes educator, pharmacist or Diabetes Canada website.

Okay, so when we get to the Internet, I said I love the Diabetes Canada website for individual drugs.  There's a very nice site and American site, but they do put lots of Canadian content on it called diaTribe.

And when I want to learn about new medications for diabetes, when I want to learn about new diabetes technologies, I often go to diaTribe.  There's no commercial presence in it, so no funding by pharmaceutical companies, device companies.  It's a lot of medical writers, and a lot of medical writers with diabetes, and they do some excellent research on that website.

Okay, so be aware of the placebo effect.  And I just put here that it can work both ways.  So sometimes people start receiving benefits from medications that really aren’t from the medication.  That's called placebo, right?  But then other people will perceive negative effects that aren't really from the medication.  So I’ll give you an example: let's say you start a new pill, and the next day you're achy.  But you've had osteoarthritis for years, and it's a rainy day and your joints are more achy.  Sometimes it's easy to scribe up to the new medication you took yesterday.  But you have to be a little bit careful about that.  So the more information you know about common side effects, the better.  And don't pass judgment on new drugs too quickly okay?  It's rare to get side effects, with just single doses of medications.  It can happen, but just be a little bit careful about scribing symptoms like joint pain that’s necessarily to a to a new medication right away. 

Now when you get medications nowadays, you often get these consumer information sheets.  You probably open them up, maybe you’ve read them, they can be really scary!  The problem with these consumer information sheets is they put a lot of information on them, and they don't always put the information in perspective.  Okay, so they may list every side effect that was ever seen in any trial.  But what you really want to know is what are the common ones.  And you know, not just these really rare that maybe just happened in a handful of people.  So that's where your healthcare provider, your physician, your nurse practitioner, your diabetes team, your pharmacist can help put things into perspective about which side effects are common.  Not just the really very, very rare ones.

Okay, so how do health care providers determine what are the best medications for diabetes?  We look at something called clinical trials, and physicians really like to see something called randomized control trials.  So what that means is that when people under these studies, and maybe some of you have taken part of these studies, and if you have, that's an absolutely wonderful contribution to do. But when you come into one of these studies testing new medication or diabetes typically half the people will get the drugs and half will get placebo.  Sometimes they'll get another type of medication.  Okay, but who gets which drug it's decided by a flip of a coin.  Nowadays they don't flip coins anymore, they probably have a computer generated algorithm that divides people into the two groups.  But basically it's just by chance who gets what.  And during the study we like to see that it's double blind, so that there's no bias.  People don't know whether they're getting drug A or drug B, or drug A or a placebo.  So those are the sorts of studies that in medicine, we really like to see.  Now there are sometimes other types of healthcare providers that don't necessarily, like naturopaths, they don't necessarily - they use compounds they don't necessarily undergo this very rigorous type of testing that physicians really like to see.

Okay, so how long does it take a new drug to come to market?  So typically, on average, it takes 10 years.  So the journey from initial discovery to the marketplace takes about 10 years.  They have to do very extensive clinical trial work.  They usually start in healthy volunteers, then they do studies in people with the diseases.  It's a very long, slow process to get a drug approved.  With the COVID, vaccine they actually say that the, that it wasn't the testing that was sped it up necessarily, it was more the bureaucracy approval process by the regulatory bodies that has been sped up, okay.  But anyways, the cost of developing a new medication, it's really expensive.  I said, the average cost is $2.6 billion.  So, as you can see it's a real gamble for a pharmaceutical company when they're developing a drug.  Not all of them come to market.  Some of them in the clinical trials don't work, or they have side effects that they weren't anticipating.  So it's a big investment for a pharmaceutical company to bring a new drug to market, and a long, slow process.

Okay Sometimes I get people when they come in, they say to me I think my doctor’s using me as a guinea pig to try out new medications.  But just remember that if you're prescribed a drug that you have to get at a pharmacy, that that has been very rigorously approved by Health Canada.  They've gone through all those clinical trial data, they've looked at all the safety data.  But typically these trials have been done on thousands of people before they get to the approval stage.  So you're getting a drug like that you can really trust in Canada that it's undergone very extensive testing.  If you are trying a drug that's not approved yet by Health Canada, and that's part of what's called a clinical trial.  And if you're taking part in a clinical trial, and that’s a very wonderful contribution to do, and I’ve been very grateful to many of my patients over the years.  I’ve helped out with a lot of clinical trials.  But you must be signing a consent form.  And nowadays, consent forms typically are very long.  They’re several pages long, you have to have signed and said that you understand that this is part of a research initiative.  The other thing is that if your doctors trying to talk you into new medications, that's probably a good sign!  That's usually a healthcare provider that's keeping up to date, and they're looking at new medications, they’re looking at the potential benefits, they might have and they're offering these to you.  So, as I say, if a doctor is wanting to switch your diabetes medications or your blood pressure medications, that's often a really good sign that this is a physician that's keeping up to date.

Why your diabetes medications less expensive and Canada than the US?  Well, we have a regulatory body in Canada called the Patented Medicine Prices Review Board.  And they actually set maximum prices that can be charged for drugs under patent.  Now under patent means that the pharmaceutical company making this drug - they get 20 years where they can't have any competitors.  This is the way that they have of recuperating those very, very expensive costs of bringing new drugs to market.  But this body that we have in Canada is really phenomenal.  We should be proud to be Canadians because they really do regulate prices much better here than, for example, with our neighbors in the US.  And maybe you've read or talk to Americans talking about the incredibly high prices they pay for their medication.  Sometimes it's like three to four times what we pay in Canada, so, as I say, proud to be a Canadian here.  Medical information is changing super rapidly nowadays.  It is just phenomenal in the diabetes field, how many new papers are coming out, how many new studies all the time, and it is really hard for healthcare providers and for people with diabetes, to keep up today.  

So Diabetes Canada plays a really important role in helping healthcare providers, and increasingly people with diabetes like events like tonight.  With keeping up to date, about changes with medications.

Okay, so Diabetes Canada publishes these guidelines historically every five years, but recently it's become apparent that five years is too long again.  And now they're updating chapters every year.  They just can't wait five years with this explosion of medical knowledge.  This is available on the Diabetes Canada website, and people with diabetes can see these same guidelines that health care providers are using.  In effect, at the start of every chapter, there are key messages for people with diabetes written in lay language to help people understand what the messages are in these chapters.  They undergo very rigorous review, and we can be really proud of these.  These are recognized and actually used and respected around the world, and any donations you give to Diabetes Canada, they really, they help to fund this very, very important activity.

So what's the drug that's most commonly used first t0 treat someone with newly diagnosed type two diabetes?  So hopefully you know the answer to this, and hopefully a lot of you are on this medication, but it's a medication called metformin.  And metformin works on the liver.  It turns out the liver, when you eat, it stores a lot of calories.  And then when you're not eating, it breaks down the sugar stores, so that when you're fasting overnight, it's releasing the small (amounts of circulation) small amounts of sugar into the circulation.  And what metformin does is it just slows down how quickly the liver is releasing that sugar.  It makes your body more sensitive to its own insulin.  Metformin takes a few days to start to work.  And it comes from something called the goats root. So showing you a picture there it's quite a pretty plant there, but that's where metformin historically was isolated from.  And it's a medica… it's a pill.   You don't need to take it as an injectable.  So is it safe with other health issues?  Well, if you develop significant kidney disease, metformin has to be stopped, and as the kidneys start failing, sometimes the dose has to be reduced.  It's not safe for people with significant liver disease, people with heart failure.  It's typically held around the time of surgery, and it's also held if you get any X Ray procedure where they have to give you a contrast die.  So some X Ray procedures you'll get an injection of a dye that can contains iodine, and metformin it needs to be held at those times.  Typically people will stop it for a couple of days before the procedure, a couple of days afterwards and then they'll restart it.

Are there any additional benefits, or in this case, why is it the number one drug?  So it's been around for over 60 years.  Very, very popular first line drug.  Well people like it because it's inexpensive, doesn't cost a lot, they've had years of experience with it, so people know how effective it is and they know how safe it is.  It has very long lasting blood sugar lowering effects.  People on this medication can lose a bit of weight. It typically does not cause low blood sugars when it's used by itself or in combination with many other types of glucose lowering medications.  And it's also used to treat other conditions like pre diabetes - people who've not developed full blown diabetes yet, people with gestational diabetes, women with a condition called polycystic ovary syndrome.  So metformin is used in other conditions besides diabetes.  So when should you take this medication?  You should take it with food, and that's to help avoid heartburn.  And you're also supposed to stop it if you get an illness where you can't keep fluids down.  And I’ll show you a little handout later on in the talk about other types of medications that should be held when you get one of those illnesses.  Common side effects - they tend to be transient.  They tend to be what we call GI side effects, and affecting the gastrointestinal tract.  So some people notice their stools become looser.  Some people will get a mild nausea.  Other people will be a bit more severe.  Some people will get bloating, abdominal cramps, diarrhea.  So to try and prevent this from happening, most physicians will build the dose up slowly over a couple of weeks.  And then, occasionally, it can cause low vitamin B 12 levels.  So if you're an older person um that may be something that your doctor may want to check periodically - if you're on metformin they may want to check your vitamin D 12 level.  As I say, it's really inexpensive, it's covered by most of the provincial formularies.  Things like the Ontario Drug Benefit formulary - that means it would be covered for people over 65.  It's covered by private drug plans.  So about a year ago, many brands of metformin were recalled, and this is because they had unacceptable levels of a compound called NDMA.  Now this happened with some other medications.  Another big example was a medication called ranitidine or Zantac that's used to treat heartburn - same thing that it disappeared for several months last year because there had been some testing to suggest that it had high levels of this and NDMA as well. But now any metformin that you're getting on the market has been tested, and has acceptable loads of NDMA.  So if people are saying to you I’ve heard metformin causes cancer that's not true.  There were some brands that were recalled because they had a potential carcinogen, but any brands on the market right now are considered to be safe.

Okay, so now we're getting on to our next class of drugs, and maybe some of you are on these are called SGLT2 inhibitors.  And as you can see they all end of the name gliflozin.  So the first one is the generic name I’ve listed here.  And then in the brackets is the brand name  where you'll see in the big letters on the box.  So how do you pronounce these?  It’s the hardest part for a lot of my patients during virtual care during the pandemic.  They're reading their medications to me and they're really struggling to pronounce these words.  And it's even hard for healthcare providers.  But the first one to come out in the market is canagliflozin.  And when people were teaching me about it, they said, think of Canada's frozen, Canada's frozen, canagliflozin.  And then it got easy – dapagliflozin, empagliflozin, you know so that's your hint to pronouncing your “flozin” drugs.  Or you can just use that “Invkana, Forxiga, Jardiance.  Okay.  These medications are really interesting in that they work on the kidneys.  And what they do is they make you pass more sugar in your urine.  So normally the kidneys are actively absorbing sugar, and these drugs make you not absorb the sugar and excrete it in your urine.  The studies have shown that it lowers blood pressure, and it also helps people lose weight.  So many people lose about four to five kilograms with these medications because you're losing sugar in your urine, you're losing calories as well.  And it's interesting, but this this actually was identified, these classes of drugs, from a compound in the bark of apple trees.  So there's an apple tree connection with the SGLT two inhibitors or gliflozins.  And they’re pills.  Are they safe with other health issues?   Um, as the kidneys fail, these medications need to - they stop lowering blood glucose.  So you need pretty good kidney function for them to have glucose lowering, weight loss effects.  As your kidneys fail though, they found that that maybe they don't lower sugars, maybe they don't cause weight loss anymore as is the kidneys start failing.  But they seem to slow down the progression of kidney disease.  So that's why they're often kept going and often used for people with kidney disease as well.  So the kidneys start to fail, they won't lower sugars, they won't help with weight reduction, but they will help prevent the kidneys from failing.  And we're going to look at that a bit more a little bit later on in the talk.  And then, are there any additional benefits?  They have low risk of causing low blood sugars.  Um, and the studies are suggesting that they can reduce the risk for having cardiovascular events.  These are things like heart attacks, dying from a cardiac event, having a stroke.  They can slow down kidney disease for people with diabetes, and they can also prevent the risk for being hospitalized for heart failure.  So nowadays it's becoming apparent that they're more than just blood sugar lowering medications their blood sugar lowering medications with added benefits okay Cardio Reno benefits like column benefits for the heart for the circulation for the kidneys.  And this was a real surprise!

So these slides get really complicated. I’m going to walk you through them.  But many years ago, there was a diabetes medication called Avandia, and there were concerns that people who took Avandia might have a higher risk of having cardiac events - heart events.  So, at the time, the regulatory bodies in the States it's called the Food and Drug Administration, and Canada it's called Health Canada, they said any new diabetes medications that come out, we need to know that they're safe from a cardiac point of view.  So they said, you have to do the safety studies, you have to give them to large numbers of people, half of them will get the drug, half of them will get placebo.  And then you got to see them regularly.  And you got to tell us whether they get any increase in things like heart attacks and strokes, and dying from cardiac causes.  So one of the first companies to do one of these studies was with a drug called empagliflozin or Jardiance.  And not only were they able to show that it was safe, but there was a real surprise.  They actually showed that it helps prevent these things.  So when you see these two lines, if there's a difference between people getting the placebo or dummy pill, and people getting the drug, that's a good thing.  And what you want to see is that the curve starts to separate early out.  That means the benefits are happening really quickly - you don't have to wait years to see it.  So you see that red line?  You can see how it starts to separate out from the black line the placebo line, and it was a 14% reduction in people dying from cardiac causes, having a heart attack, having a stroke.  So this was a real surprise.  Not only was this drug helping people lose weight and bringing their sugars down, but it was also reducing their risk for cardiovascular events, and that was super, super exciting at the time.

We like to see as physicians - we like to see this happen with other drugs in the same class - other gliflozins.  So there was another drug called canagliflozin, and other one in the same class called Invokana, they did the same study.  And as you see, huge numbers of people over 10,000 people.  They're taking part in these studies for up to six years – it really cost these pharmaceutical companies a lot of money.  It's a big commitment from the participants.  Really grateful for them to taking the time to do this.  But you can see these lines separating out.  14% reduction again.  Same thing as that other drug.  And when you see the same thing happening with drugs in the same class, that's a really good thing that makes it think it's not just a fluke okay.

The other big thing that started showing up really quickly was not only people not dying of cardiac events or having Mis or having strokes.  But a really big thing that was happening was people were having being admitted less often to hospital with heart failure.  Now, I have well, maybe I should tell you that's probably too personal story – we’ll skip that one.  But I was gonna tell you about one of my relatives, but we'll leave that one alone, okay.  But, but you can see these two curves starting to separate.  A 35% reduction in people getting this empagliflozin, or Jardiance, having to be admitted to hospital for heart failure.

So it looks like these drugs are doing more than just lowering sugars to have these benefits - they're probably having other benefits to reduce the risk for cardiac events, hospitalization for heart failure.  And boy is this slide ever complicated, but it's just showing you that they've seen it now with all three drugs in this class.  So not just that one I showed you in the last one, but they're also seeing it with the canagliflozin and dapagliflozin.  They're all having very significant impact in reducing the risk for hospitalization for heart failure.  They doing more than just lowering sugar.

So more recently they've gotten a bit more ambitious, they said well why, maybe they help people that don't even have diabetes.  So recently these the same drugs have been tested in people without with without diabetes who have heart failure.  So in this particular study here they gave it to a large number of people with heart failure.  Some of them had diabetes, some of them didn't have diabetes, are able to show that this drug still had benefits, even for people without diabetes in reducing their risk for being hospitalized for heart failure.  So that's huge, huge.  And then, here we like to see the same finding with multiple drugs here, it is with another competitor drug empagliflozin.  Same thing they did it in people with or without diabetes, showing that it can even help people without diabetes.  So maybe you have relatives with a history of heart failure that are being offered your diabetes medication you're saying why you going on this?  And they're saying my cardiologist said it was going to help with my heart failure as well.

 And then the other big thing they started seeing in these studies was not only did it reduce the risk of  cardiac events and reduce the risk for heart failure, but it also shows the ripples show that it's slowed down the progression of kidney disease for people with diabetes.  So absolutely amazing, amazing finding.  Another added bonus surprise.  And, recently people have said, well why don't we start testing it in people without diabetes?  And they were able to show the benefits.

So now, you may have friends that have kidney disease from other causes besides diabetes.  They may be coming back and telling you their nephrologist who started them on the same diabetes medication they're on, and this is because it can also slow down progression of kidney disease.

We want you to take them typically a gliflozin in in the morning, you can take it with or without food.  But these drugs, it's really important not to take them if you get an illness where you can't keep fluids down.  Because remember you're excreting the sugar out your urine, but sometimes water goes along with that sugar, and so it can dehydrate you.  So if you have an illness, where you can't keep properly hydrated it's really important to stop this medication.  So there is a handout on the diabetes Canada website and maybe your physician has given it to you, but everybody with diabetes, this is a great hand out to them to talk about with your health care provider.  And it tells you about which medications which diabetes medications should be stopped if you get one of these dehydrating illnesses. And, and then physicians are talking about this thing called the SADMANS list.  The final S here is those SGLT2 inhibitors.  And then there's the metformin.  You know about the M now, and you know about the S.

And that's a really good handout that you should have if you're on glucose lowering medications.

Common side effects.  Well, increased sugar in the urine, and if you get a lot of sugar in your urine for women, one of the risks is yeast infections.  So women, about 10% of women, will get a vaginal yeast infection.  Now, they tell us in the studies that it's typically just one, it's typically at the start of therapy, but there are some women where it's a recurring problem.  And if that's an issue for you, this may not be the right drug for you.  Men can get yeast infections on the tip of their penis.  They look like itchy red rashes on the tip of the penis, and it's good if your physician warned you about that because it's kind of embarrassing, you may not relate it to the new diabetes medication you started.  It will clear up with a anti yeast medication Monostat, Canestin and that you can buy over the counter at the pharmacy.  If you want to make the risk of getting an infection in your in the tip of your penis less, it's really good to keep it dry keep it clean.  Wipe after you go pee and keep it clean.

These medications can make the blood pressure go down.  Now sometimes it's a good thing, and I said, your blood pressure's high, it will help bring your blood pressure down.  But sometimes for some people it might lower the blood pressure too much.  So if you experience any lightheadedness, particularly with standing up, that's something you're going to want to talk about with your health care team.  And other blood pressure medications sometimes need to be adjusted if you're on this class of medication.

 And then there's one really rare side effect called diabetic ketoacidosis.  And this can occasionally happen.  It typically happens in people that have kept taking the medications when they've gotten a dehydrating illness.  So if you really want to reduce the risk for getting this diabetic ketoacidosis, this is uncommon side effect with this class.  Make sure you stop it when you get a an illness where you're vomiting, you can't keep fluids down, you've got diarrhea.  And it presents with something you typically will come in with nausea, vomiting, abdominal pain, increased sleepiness.  So thats a very rare side effect, but it's one of the reasons why I’m learning about those sick day rules, and that sick day medication list is so important.

Okay, and then maybe you've heard about this one.  There was one early study.  And there was a higher risk of lower limb amputation.  Now it only has been seen in one study, with one of these medications.  And in many, many studies, in large numbers of people, it has never been seen in those trials.  But many healthcare providers, and I think this is the right practice, won't prescribe it if there's been a history of an amputation within the past 12 months, if you've got an active skin ulcer on your on your lower extremity, you've had a history of infection in the bone in your feet, gangrene, they won't give it to you.  So if there's been an amputation, not for a year, if there's a foot ulcer, not till it's cleared up for six months.   And many healthcare providers, this is good diabetes practice in general, will do a foot exam at every visit.  And if they find any of these things, they'll stop the drug until the ulcer’s cleared up.

The drugs are expensive, but they are covered by the provincial formularies, and most private drug plans.  And the big message with the gliflozins is that they have those added benefits.  Remember, reducing cardiovascular events, slowing down kidney disease, reducing heart failure admissions, helping people lose weight, lowering A1c, lowering blood pressure.  So there's all sorts of added benefits with this class, and that's why they're very, very popular drugs these days – the gliflozins.

Now we move into another really popular class nowadays, and they're called GLP-1 receptor agonists. And they in one word glutide.  Okay, and how do you pronounce these?  Drugs are pronounced multiple ways, but I think it's easiest to do the start and then the glutide.  So one of the, for example, I put down here semaglutide.  You start with a sema glutide.  Lira glutide.  Dula glutide.  So that's just your hint for how to pronounce them.  Now here's another big hint on this slide.  If you see lots of drugs in a class, it's usually a good sign that this is a really good class.  I mean pharmaceutical companies, if they see there's lots of promise, they're going to want to make lots of competitor drugs, because they know this is an effective class that health care providers are going to want to use.  So when you see lots of names here that some that's a really, really good sign okay?  Now, as I say, I’ve looked at them alphabetically and maybe you'll recognize some of them.

Okay, so let's go through this.  How do they work?  Okay this one's a little bit complicated.  They mimic a natural gut hormone.  So every time you eat, your gut puts out this gut hormone called GLP-1, and what GLP-1 does is it stimulates your pancreas to put up more insulin.  So they're mimicking that natural gut hormone.  They also lower blood pressure, and people lose weight on these medications.  Here again, though they’ll about four to five kilograms.  Some people will lose even more than that.  They often suppress appetite.  So they make you feel full - less hungry.  So they're very, very effective agents in promoting weight reduction.  Most of them are injectable.  One pill version came out in the market, just within very recently, within the past year.  Okay so most are injectables, but there is a pill version now.

Okay, where do they come from?  Well it turns out that there's a there's this reptile here, called the Gila monster, and this lizard only eats four times a year.  And when it stops eating, it shuts down its pancreas.  So it doesn't put out any insulin.  But when it starts to eat, it starts to release this natural gut hormone to wake up the pancreas, and get the pancreas to start making insulin again.  So people are able to isolate this compound initially from the saliva this this lizard.  And nowadays, many of the brands are based more on, thy resemble more than natural human form of this hormone.

Are they safe?  These drugs aren't actually broken down by the kidneys, so you can use them with very, very low kidney function.  So that that's a nice thing about the class.  All may carry a low risk of causing low blood sugars.  And here again, there was a surprise!  Remember those big cardiovascular safety studies, Health Canada, FDA saying we got to know these drugs are safe, they don't cause any cardiac events.  When they did these studies with these drugs they were just stunned, once again, to see that they reduced the cardiovascular events, heart attacks, strokes, dying of a cardiac cause.  So it was a real surprise, and it showed once again that they're more than just blood sugar lowering medications.

So here's with one drug called liraglutide or Victoza.  And they were really surprised once again.  As you can see, the two curves you can see how they start to separate out, and early on.  That's really promising.  23% reduction in cardiovascular death, heart attacks and strokes.  Was a surprise.  Added bonus.  Amazing.  And then this slide looks so bloody complicated, but it's just to tell you they've seen the effect with multiple drugs in the class.  And they've also shown that benefits don't just happen in people that already have heart disease, but they can also see benefits in people that have what they call cardiovascular risk factors.  So these are people that don't have heart disease yet, but we think it's really likely they're going to get it in the near future.  People who smoke, people who have high blood pressure, people who have high cholesterol, people with weight that they carry in the centre part of their body.  So benefits seen for all those types of people.

When should you take them?  They come in these injection devices.  Many of these drugs nowadays are taken just once a week.  Um they're pretty easy to use.  So they are - some of them are injectables - it's kind of scary to do an injectable for the first time.  And it's a little bit hard during the pandemic sometimes to get the training that you typically would get in person at your physician's office, or at a Diabetes Education Centre.  But many diabetes education centres are still open.  They're still able to see you.  Your pharmacist can teach you how to do an injection in the pharmacy.  You may have a relative that's already on this type of medication that could show you how, and there's all sorts of amazing online videos that you could watch as well.  And you could do the classic Youtubes, or for this particular drug Ozempic, they actually have a website.  Many of the companies have websites where you can log on, and you can watch videos, you can read pamphlets - they've created these for use during the pandemic.

Now, as I mentioned, there is a pill version of one of these GLP-1 receptor agonists.  It's called oral semaglutide, or Rybelsus.  It's taken every day.  You have to take it first thing in the morning on an empty stomach, and you have to take with just a SIP of water.  You can take it with a lot of water.  And then you have to wait 30 minutes to eat.  So if you're really nervous about an injection, you can take the pill version.  Or if you're not nervous, one injection once a week.  The injectable one that you take once a week is covered under the provincial formulary.  The pill version is not covered at the present time, so you would need private insurance to be able to consider the pill version.

Most common side effects: nausea, vomiting, diarrhea when you first start the drug.  So they say that it typically tends to be transient - disappears over a few weeks as your body gets accustomed to it.  With many of the drugs in this class, the dose is built up slowly over time.  Now the side effects from my patients - they're typically the worst the day after the injection.  So I say be prepared for that.  If you do the injection, be prepared that you might have side effects the next day.  And one of the things that really helps us to eat lightly the day after the injection.  So it’s not your day to go and eat fast food or a big meal at a restaurant.  Eat lightly.  So that that can really help as you get used to these medications.   Side effects that the nausea occurs in up to 20% of people - there are lots of people that never noticed a thing.  Occasionally there have been reports of things like gallstones, pancreatitis.  And then this is the thing that scares most of my patients when they read those consumer safety sheets.  It says not to use it if  there's a history of medullary thyroid cancer, and people get really scared.  Turns out medullary thyroid cancer is a very rare type of cancer.  It tends to run in families.  The studies that show these higher rates of thyroid cancer, they tended - they were done on rodents.  And they were at a hundred times the dose that are used in humans, so there.  And all the safety studies that have been done in humans, they haven't seen an increase in this rare type of modality thyroid cancer.  It comes from very early rodent studies and, as you say medullary thyroid cancer, you may be aware of thyroid cancer in your family, but just double check that it was this medullary.  This tends to be a very, very uncommon type of thyroid cancer.

They're very expensive, but one of them is covered under the provincial formulary now, and most private drug plans will cover them as well.  And here again, the added benefits, more than blood sugar lowering medications.

And now we get into the drugs called the gliptins.  So we have linagliptin, saxagliptn and sitagliptin - the DPP4 inhibitors.  And remember we were talking about that natural got hormone, the one that the lizard is making in its saliva and how it stimulated your pancreas to put out insulin?  Well, that natural gut hormone gets broken down by an enzyme, so it doesn't stay in the circulation for that long.  So these drugs work by blocking that enzyme.  They make that natural gut hormone last longer.  And they’re pills. And, here again, Diabetes Canada, little bit of a pitch for them.  Much of the work in isolating that gut hormone, and developing these GLP-1 receptor agonists and these DPP four inhibitors was done by a researcher in Toronto, Dr. Dan Drucker.   And he received lots of funding from Diabetes Canada over the years.  So this is, he's really puts Canada on the map, and really benefited from Diabetes Canada’s support.

They do need some dose reduction as kidneys fail.  And they, once again, they're very well tolerated, they don't cause low blood sugars, they don't cause any weight loss.  So remember those gliflozins, the one on the kidneys, the glutides, the ones working like the natural gut hormone?  They can be associated with weight reduction.  These ones are just weight neutral.  You won't lose weight, you won't gain weight. 

Taken once a day, with or without food.  Incredibly well tolerated.  So no common side effects with these drugs.  They're a little bit less expensive than some of those other drugs we talked about, and they typically are covered under provincial formularies, private drug plans.  But they don't have those surprises - those added benefits, okay. 

Some of you may be on sulfonylureas.  Um, gliclazide, Diamicron, is typically the most popular.  There's an older one called glyburide.  Gliclazide is the preferred one nowadays because studies have suggested lower rates of low blood sugars with this class.  They stimulate the pancreas directly to release insulin.  And they’re pills.  As your kidneys fail, you need a dose reduction.  They start to work quickly.  They're not very expensive, they're just a touch more expensive than metformin, but much cheaper than a lot of those newer drugs we've talked about.  Typically they're taken in the morning at breakfast time.  Common side effects: they can cause low blood sugars.  And they can cause weight gain.  And that's why they're not as popular now.  Those other drugs – the gliflozins, the glutides, much, much more popular because they have those added benefits - that weight reduction, that more potent on lowering blood sugars and A1c.  And they can have those added benefits.  And these drugs little older fashioned, some weight gain risk, some hypoglycemia risk.  But they're cheap.  So if money is a problem, you don't have a good drug coverage, your physicians still might choose this class of agents because they're not very expensive and they're covered by provincial formularies.  But if you're on these drugs now, you might want to talk to your healthcare provider.  You might say, would there be any benefit for me trying a newer diabetes medication?  One of those ones we talked about before.

Now, we’ll be moving on to insulin at this point.  And just to remind you, many people with type two diabetes eventually require insulin.  And if you start with insulin with type two diabetes, you typically start with a long acting insulin once a day, and then, if that's not enough they'll add an insulin every time you eat a meal.  Meal time insulin they call it.  Now people are often really reluctant to consider insulin. And some of the common myths are that, hey if I need insulin I’m a failure.  The right thing is that it's just type two diabetes tends to be progressive.  Sometimes over time, the pancreas just loses its ability to put out insulin and it doesn't matter how many medications you take that are trying to stimulate that pancreas to put on insulin.  The pancreas just can't make that insulin anymore.  Sometimes people have this idea that insulin causes complications or death.  Often, historically, insulin is left till really, really late.  And sometimes people have very advanced disease, multiple complications, their doctor says it's time to start insulin.  And then maybe they die, or they develop a severe diabetes complication.  Often if the medication perhaps had been started earlier, then the complications could have been avoided.  And then many people are worried that they're going to gain weight with insulin. People can gain weight with insulin.  Insulin helps your body use its food more efficiently.  But if you're careful about how you eat, you work with a dietitian, then you could really minimize that weight gain.  And then people are worried about injections being painful.  The needles are very small that are used to administer injections.  Injectable medications like insulin or those glutides.  I’ve been told that the needles are typically the sizes of mosquitoes probiscis.  I don't even know how you pronounce it – probisci?  Okay, but they're very fine, they're very, very fine needles.  Um, typically shouldn't hurt.  People say fingerprints hurt a lot more.  So don't be frightened about injection pain.  Most of my patients are actually stunned when they do their first injection and they see how painless it is.

OK, and then combinations.  Boy, you can do just about any combination under the sun now, and there are advantages.  So if you're typically not getting good control with one drug your health care provider will prescribe other drugs.  They often work really well in combinations because they're all targeting different problems with the diabetes.  They can be used in a variety of orders.  If you use those glutides and those gliflozins together the SGLT2 inhibitors, GLP-1 receptor agonists sometimes you can see even additional weight loss above one agent alone.  And then they make combination pills.  So often you'll see two drugs added into the same pill.  That's done to reduce the pill burden to make it a little bit easier, so you don't feel like you're just rattling every time you walk with the number of pills you take.  So those combination pills are often very handy and in reducing pill burden.

So how do we put it all together?  This part looks scary as anything, but this is what Diabetes Canada puts out for healthcare providers.  They give them these flow charts, and this is what your physician is probably looking at when they decide which medications to use and which ones to offer you.  So they say this is someone who just got diabetes, they say, remember you know, look at their blood sugar control, ask about for kidney problems, heart problems.  Remember to refer them to a Diabetes Education Center.  Remember to encourage people to work on - they call them healthy behavior interventions - you want to work on eating well, getting your weight under control if you're overweight, starting some regular exercise.  And then here - there it is - metformin popping out to them saying yeah use the old standard, inexpensive, safe drug that's been around forever.  And then it says - they go on to another table - and the table says if you're not getting the sugars at target, or if people have.  I’m putting in the little box here and paraphrasing it for you.  If they have cardiovascular disease: so that would be you've had a heart attack, you've had a stroke, you've got hardening of the arteries in your legs, you've got kidney damage, you've got heart failure, you've got a cardiovascular risk factor, you’re a smoker, you've got the central weight, you've got high blood pressure.  It says go down and use a drug that will have benefits.  So then they go here and they can see the big thing in this table.  Remember those GLP-1 receptor agonists, the glutides, and the SGLT2 inhibitors (the gliflozins), as you can see how they just say, think about these drugs if you've got people with heart problems, with heart failure, with kidney disease.  These are good drugs to use.  Remember those additional benefits.

 And then they say if people don't have heart disease, kidney problems, heart failure, then ask your patient what are their preferences, what do they want what are their priorities?  Do they want to lose weight?  Do they want to have low sugars?  Are they at risk for certain side effects?  What's their drug coverage like?  Are they able to do an injection?  Do they have the dexterity?  And are they planning a pregnancy?  What's their kidney function like?  But there again there's this new drug showing up.  Those GLP-1s, SGLT2s, who are saying that these are drugs that can really help people lose weight and bring the sugars down.  And then there are some of those older drugs like sulfonylureas that show the risk of weight gain and having low sugars.

And we're getting close to the end.  Um, so just remember you need more medications over time.  It doesn't mean you're a failure, it just means that diabetes tends to be progressive and people often need more than one drug over time.  And your part: take medications consistently.  Be up front of you're having trouble doing this.  It's much easier just saying I’m no good at taking my pills.  Your healthcare team may be able to come up with strategies to help you overcome some of those barriers you face.  And just a reminder to always bring your medication list, your pill bottles to appointments.  Don't let your diabetes care slip during COVID.  Try and keep up to date if you can.

Okay, so that brings us to the end of the presentation, and then I see Dr.  Noronha’s come on, and he's going to help chair the question period.  And he's a primary care provider with a big interest in diabetes, so maybe if I get stumped he'll help me out with some of the answers as well.

Oh - you're on mute still, Dr. Noronha.

We can try and read your lips it's just a little bit harder!  Now we can hear you now.

And we can't hear you again.

Dr. Lionel Noronha: Can you hear me now?  Yes, okay fantastic.   Sorry for the technical challenges so...

Dr. Robyn Houlden: Actually, you’re muted again, so maybe I'll just throw some questions out there?

Dr. Lionel Noronha: Last chance or take over!  But really quickly:  great, great speaker.  Lots of information.  You know,  I'd like to just point out one thing.  The treatment of diabetes always starts with diet and exercise, especially Type two diabetics.  And we were kind of assuming that this is a topic specifically on therapeutics referring to medications if anyone's wondering.  But it was really reassuring to realize through your talk Dr. Houlden that a lot of blood sugar medications have these ancillary benefits for cardiovascular disease, kidney disease, heart failure.  And you know weight loss to which is you know, a point in which a lot of years start to open. 

Now, we do have some questions.  One really good question was: Due to my diagnosis of diabetes in November 2020, and my recent congestive heart failure diagnosis in March of 2021, is there any connection?

Dr. Robyn Houlden: And there is!  So when we think about complications with diabetes, we think about the ones affecting the heart and the blood vessels in the body, and they call those macrovascular cardiovascular complications.  We think about diabetes hurting the smaller blood vessels in the body.  And that's things like eye damage, kidney damage, nerve damage.  But one thing that isn't always appreciated is the higher risk of heart failure.  And people with diabetes are much more prone to um to heart failure than people without, and it's often missed and not well diagnosed.  So there's a big, big move right now in the diabetes community to remind healthcare providers about screening for heart failure and being aware of that risk of heart failure with diabetes.

Dr. Lionel Noronha: Fantastic.   There was nothing question on metformin:  Does metformin need to be stopped if you have congestive heart failure?

Dr. Robyn Houlden: So if you have really severe congestive heart failure, you’ve been admitted to hospital, you're being admitted perhaps to a cardiac coronary care unit or an icu, metformin is stopped in those scenarios.  But if you've got heart failure on a day to day basis, which is well managed with other medications, you can be on metformin.  It's just in really extreme decompensated or hospitalizations for heart failure that it’s stopped.

Dr. Lionel Noronha: Thank you.  There was a question/comment: I heard in Europe there are being suggestions that metformin may not be the ideal starting drug for all diabetics - Type two diabetics - what are your thoughts?

Dr. Robyn Houlden: So, this is a big area in our diabetes community right now.  At our meetings we have big debates on it.  So there's sort of two schools of thought.  One is that all the studies with those newer drugs I was showing you - they typically enrolled people that were already on metformin.  So people saying well but in these studies, they were already on metformin, these are add ons, so let's keep using metformin first line.  But other groups are saying, but these benefits for on the heart are just so amazing!  Why don't we start with them?  And, and I think there's more and more of a move to start these drugs that have these cardiovascular benefits earlier.  And so I think that we're just really trying to encourage healthcare providers to consider these drugs even earlier.  And it came on that table you saw that even if somebody's blood glucose is already at target - if they had cardiovascular disease, they had heart failure, they had kidney disease, that you should still be using these drugs - even if the sugars are at target.  Even if that meant adjusting other medications that they're already on (other glucose lowering medications).

Dr. Lionel Noronha: Thank you.  There was a question here: I think the person basically put up their scenario - I have type two diabetes, on sitagliptin 1000 milligrams twice a day.  Invokana 300 milligrams daily.  My A1c, that's my blood sugar, overall control indicators 7.9%.  I also have liver myofibrosis, chronic arthritis, heart disease, but no peripheral artery disease.  That’s a lot of technical details, what should I asked my doctor to review?

Dr. Robyn Houlden: So that was kind of a lot.  But their A1c is 7.9%.  And the dream for type two diabetes is trying to get it under 7.0%, and if you can, even under 6.5%.  Okay, so they're not a target.  They are on one of these newer gliflozin drugs, so that was great.  They’re on the one called canagliflozin, or Invokana.  And they were on a drug called sitagliptin, and then I can't remember whether they were on metformin or not, but that.

Dr. Lionel Noronha: metformin was just sitagliptin and Invokana of which is kind of…

Dr. Robyn Houlden: One thing they might want to consider - and maybe part of this all those complications you were talking about that I missed - but a really powerful combination is to add in one of those GLP-1 receptor agonists.  So if you were to take your sitagliptin and replace it with a GLP-1 receptor agonist.  So something like a glutide, remember?  Semaglutide, um, duaglutide, that might really help bring that A1c down.  It might help them lose weight.  And it's safe, irrespective of degree of kidney function, so that's what I would think.  Now typically that sitagliptin, Januvia, the DPP-4 inhibitors aren't used if you're on a GLP-1.  They're working kind of too similarly through the same pathway, but definitely those GLP-1s are a lot more potent.  So I would be asking about whether you would be a candidate for a GLP-1 receptor agonist.

Dr. Lionel Noronha: Great.  Thank you.  There are a couple more questions.  Before I ask those I just want to remind our attendees today thank you for coming, but please fill out the evaluations to get some good feedback for developing future programs.  So another question was:  Can diabetes, the diagnosis of diabetes be reversed?

Dr. Robyn Houlden: Um, yeah that's the most exciting area right now is that your goal shouldn't be necessarily to get your diabetes under control, but your goal is to reverse your diabetes.  And you're going to accomplish that with your lifestyle: with your losing the weight, and your exercise.  And often people will are able to come off glucose lowering medications.  So, yeah, big area right now.  Hot area that we shouldn't just be satisfied with controlling diabetes, but for many patients, if possible, we should be aiming to achieve diabetes remission.  And you see some patients, don’t you Dr. Noronha?  People coming in that just “wow” you.  They embrace this, and they work hard at it, and they're able to accomplish this.  But the other message was “no shame!”  Diabetes is a hard disease to care for and to live with, and it's often progressive.  So there's no shame if you need more help over time.  Don't worry about that.

Dr. Lionel Noronha: Yeah, no.  Thanks so much Dr.  Houlden.  It's an exciting time again in diabetes, because you know 30 years ago we didn't have these medications.  We're seeing people not progress with their diabetic control - sliding so quickly.  You know we're seeing evidence that we're reducing all these other events - helping people with weight loss, and you get them out of that negative cycle, as you see, even more than I.

Yeah.

That's it for the questions.  So I'd like to really just wrap up now.  And be just a tiny bit over time, but please do your evaluations.  I’d like to point out our next session is on Saturday April 10th at 10 to 11 in the morning.  And that’ll be with Lori Berard, the Canadian Diabetic Educator of the year, and Dr. Steele a nephrologist who has a passion in diabetes.  He’ll be talking about monitoring and the top 10 things a diabetic should know.  So I'd like to first thank my team who helped put this together.  They're very humbled and requested not to be named. I like to thank Diabetes Canada and Grace Leeder for her technical support.  Very much, and most especially, I’d like to thank Dr. Robyn Houlden.  That was a wonderful talk.  I’ve heard you many times and it's always a pleasure, and I learn something myself every time.  And also I’d like to thank all the attendees tonight for coming out and your great questions.  Thank you very much.  And hopefully see you next time on Saturday April 10 Thank you again, Dr. Houlden.