Wegovy® - A new era in obesity management

In a world where the narrative around obesity has often been clouded by misinformation, it's time to shed light on the truth with evidence and science. Obesity is not just a matter of willpower; it is a recognized chronic disease closely linked to many of the top health issues that significantly impact health benefit plan costs in Canada. 

Join us for an enlightening webinar that will change the way you think about obesity, its management, and its impact on workplace health.

The webinar covers:

  • The Science of Obesity: Delve into the comprehensive science and evidence that classify obesity as a chronic disease.
  • Linkages to Chronic Illnesses: Explore the direct connections between obesity and other chronic illnesses that are major drivers of health benefit plan costs.
  • Evidence-Based Management: Discover the benefits of a holistic approach to obesity management - from lifestyle modifications to medical interventions and the benefits of Wegovy® as an obesity therapy.

Sponsored by:

 

To view full transcript, please click here

Manal Ali  00:00:03 

Good afternoon. Welcome and thank you for joining us for today's webinar. We go the a new era in obesity management sponsored by Novo Nordisk Canada, Inc. Let's get into a little bit of detail on our sponsor, Novo Nordisk is a global health care company founded in 1923 and headquartered just outside of Copenhagen, Denmark. Their purpose is to drive change to defeat diabetes and other serious chronic diseases such as obesity, and rare blood and rare endocrine diseases. I'm an ally from benefits and pension monitor and I will be your host today. Before we get started, I just have a few housekeeping items to review. If you have any questions for today's presenter, please type them into the q&a box. You can submit them at any time during today's session. We will be collecting them and addressing them during the audience q&a portion at the end of the webinar. If you have any questions for today's presenter, again, you can please type them into the q&a box. We will be launching some poll questions today during today's webinars so please pay close attention to your screen so you can participate. Now let's get to it. And let me introduce you to our speaker. Rami Halabi holds a PhD in neuroscience from the University of Calgary and an MSc in physiology and pharmacology from Western University. He is currently working as a medical science liaison in obesity and liver disease at Novo Nordisk is deeply engaged in diversity, equity and inclusion initiatives within Novo Nordisk and recognizing the pivotal role of combating disease stigma in fostering equitable health care. Rami, welcome. And over to you. 

Rami Halabi  00:01:57 

Thank you so much, Manal. And thank you very much to the organizers for the opportunity to present to you today. So, like what was mentioned, my name is Rami Halabi. I am a medical science liaison with Novo Nordisk both in the therapeutic areas of obesity as well as liver disease. And today, we are going to be chatting about the chronicity of obesity. We're going to explore a little bit on the pathophysiology of the disease as well as some options for management with particular focus on semaglutide. Okay, so just a quick overview of what we are focusing on today. So I'm going to start off by talking about obesity as a chronic disease, what the impact of weight gain and weight loss is on our health. A quick overview of what are the clinical practice guidelines, which you can kind of think of as like a blueprint that physicians and patients alike use for the management of their obesity, and then we'll focus particularly on semaglutide 2.4 milligrams, otherwise known as would go V for the management of obesity. Okay, so let's start with obesity as a chronic disease. So let's first I just want to make sure we're all on the same page here as to what how obesity is defined. So obesity is a prevalent, complex, progressive and relapsing chronic disease characterized by abnormal or excessive body fat or adiposity. That impairs health. And this definition is very important. It's the one that we use. In Canada, it's the one that is actually used worldwide across many different health agencies. So I just kind of listed a few here, not going to read them all to you. However, I have bolded, you know, just some of those specific key terminologies you'll notice, words like chronic metal condition, medical condition, chronic relapsing health, or as pathological state, progressive disease. Many different health authorities around the world have acknowledged and recognized obesity as a chronic disease, which is a very important step when we talk about decreasing social stigma surrounding wheat issues as well as addressing this with proper tools for management. So I've defined to you you know what obesity is, but how do we currently classify obesity, when we're talking about is somebody living with obesity. At this point, we do still use body mass index or BMI cut offs. Many of you will probably probably be familiar with this type of measurement. So body mass index is calculated by taking your weight in kilograms divided by your height in meters squared. And so individuals that have a BMI greater Then 25 are considered as being living with overweight. In an overweight body, however, those of the BMI greater than 30 are said to be living with obesity. Now, I fully acknowledge I'm happy to chat about this later, that BMI is not the best criteria, but it is currently the gold standard criteria used worldwide. But let's focus in a little bit then on Canada. If we look at the prevalence of obesity in Canada, keeping in mind that BMI greater than 30 as being the cut off, it's According to Statistics Canada, you know, two thirds around 65% of Canadian adults were either living with obesity, so that BMI greater than 30, or overweight, so that BMI greater than 25. In fact, obesity rates tended to be higher in smaller cities compared to our bigger urban centers. I'm just highlighting here, you know, two provinces, you'll see BC, as well as Newfoundland and Labrador. And these actually represent two ends of the spectrum with respect to the prevalence of obesity in both of these provinces. Just gonna give you a couple of seconds to think of what how you do you think that actually lands higher or lower than the national average, knowing that we're sitting around 30% of adults living currently living with obesity in Canada as a whole. In fact, BC represents the lowest prevalence of obesity sitting around 25% of adults having a BMI greater than 30, while Newfoundland, Newfoundland and Labrador with respect to the provinces sits at the highest prevalence with over 40% of adults currently living with obesity. And just something a little excerpt that I pulled from Statistics Canada from last year, this was really important because they've actually changed how they view and ident and kind of capture data on obesity, it used to be considered a just a risk factor for other chronic diseases, like diabetes, high blood pressure, heart disease, stroke, arthritis and cancers. But now they're also recognizing obesity itself is a chronic health condition. And this is very important, again, when we talk about addressing social stigmas, and providing equitable health care to individuals that are currently living with obesity. So now, let's continue along this paradigm and talk about what the impact of obesity as well as weight loss on our health. Big question, Is obesity really only a result of eating less? Sorry? Is obesity only a result of eating more and moving less? So ultimately, if you eat less and move more? Can you combat obesity? Well, we know that this is kind of an outdated statement. We there are many, many paths that lead towards somebody living with obesity. In fact, we're going to be discussing a couple of these not in any great depth, but just enough that I give you kind of a flavor of you know what type of management currently exists exists for individuals living with obesity. But we do know there's a biological component in which the brain can control eating behavior as well as appetite. Our genetics do play a role some of us are maybe more predisposed to developing excess weight or excess adiposity. We know our there are influences from psychological social as well as environmental impacts, think about the place that you currently are living or residing in what type of food access Do you have? Is it equitable? What about health care access medications that you have access to, we do know several medications are linked to promoting weight gain. So while we use them for other conditions, they are ultimately contributing to excess adiposity or increased weight gain. So that is to say everything in this image here is that it's really not just looking at eating more and moving less ultimately results in obesity. Many paths can lead towards it. And it's very important that when a healthcare professional is deciding, you know, goal planning with their patient, that they take this into consideration. So what are the complications that are current that we currently know are associated with obesity? I'm breaking this down to a number of on different levels on the body, so we have our metabolic conditions. So our cardiovascular disease, type two diabetes, infertility as well, certain cancers have been associated with obesity. We think about mechanical issues that we're that we might be facing. These can include things like asthma severity, sleep apnea, chronic back pain, even Eostre knee osteoarthritis have also been linked to, we'll be living with obesity. And on the mental health component, we do know depression and anxiety are associated with obesity. And this can go either direction, those living with obesity may have a higher prevalence of depression and anxiety. But as well, depression and anxiety may contribute to developing obesity or excess adiposity. In fact, overall, there's over 230 complications that are actually associated with obesity, they touch on every organ in our body. And it's because of that, that every medical specialty has some sort of brushing along obesity management, which is why it's so important that education with respect to obesity as a chronic health disease and condition is made aware amongst all of our health care professionals. 

Rami Halabi  00:11:28 

Okay, we're on to our first polling question of the day. So in the absence of any other metabolic conditions, so this could be type two diabetes, hypertension, dyslipidemia, or the like, does obesity increase your risk of cardiovascular disease? So you should be seeing the polling question appear on your screen? We'll give you a little bit of time to, to fill that one in. So the question is specifically asking, so this is you do not have type two diabetes, you currently are just living with obesity? Are you at an increased risk of cardiovascular disease? 

Rami Halabi  00:12:12 

So Okay, looks like we're all done. Amazing. So we have the vast majority are saying yes, it can increase our risk. And then a few individuals that said, I'm not sure, very happy to see these results. You know, I think that means this group totally acknowledges here that obesity is is not only just a risk factor, actually is a direct contributor to increase in cardiovascular disease risk. In fact, there, this has been well documented in a number of studies. So I'm going to orient you as to what what you're kind of looking at here, because there's a lot of dots, a lot of arrows. But at the very bottom row, here, we have individuals with a no normal weight. So again, we're using that BMI criteria. So BMI is under 25. In the absence of any other metabolic conditions, so somebody with a BMI under 25, doesn't have type two diabetes doesn't have hypertension. They're at, let's say, no increased risk of developing coronary heart disease, stroke, or heart failure. Now, if we look at somebody that's living with obesity, they do not have type two diabetes, dyslipidemia, or the likes of what we were just discussing, there all of a sudden add an increased risk. So here, this, the very bottom are looking at these hazard ratios. So this is how much more likely are you to develop one of these one of these conditions. And we see that across the board, obesity is linked to a higher risk of developing any one of these cardiovascular disease, suggesting that obesity itself is an independent factor here contributing to cardiovascular disease. And obesity, and all these other added risks. Like let's say the cardiovascular disease that I mentioned earlier, do have a major impact on our life expectancy. In fact, if we look at those, again with that normal BMI, so this is the BMI under 25. We expect around 80% of individuals have a chance of reaching to the age of 70. However, as we increase the obesity class, so that's to say, you know, different quartiles of what BMI the individuals are. So let's say somebody with a BMI greater than 40 are under 50. They have a 50% chance of reaching to the age of 70. So again, obesity here is linked to a decrease in life expectancy. So we're talking about you know what the impact is of obesity on our health What about the flip side? Let's say you reduce adiposity. So weight loss, what is the impact on our health at the end of the day? Well, we actually do know through a number of studies, and this is historically being done, as well as currently, in many, many trials, that weight loss leads to improved health outcomes. So as low as 5% weight loss, which is our clinically significant cut off for weight loss, this is what we aim to achieve in any type of clinical trial when we're looking at pharmacotherapy intervention, lifestyle intervention, or, or, or the likes, that fibers as little as 5%, we see improvement in hypertension hyperglycemia. But then, as we keep moving through these different, greater magnitudes of weight loss, we can see improvements in a number of other different health conditions or disease states, you know, improvement in Seattle hepatitis, which would be in its former former name as fatty liver disease, we know that there is improvement in type two diabetes management, urinary stress incontinence, and the likes, kind of mentioned a few over here. So overall, we do know that weight loss is a leading to an improvement in health outcomes. So with that, we're going to move to our second polling question because I just want to see where everybody's at. So true or false. Once obesity is established, the body attempts to promote weight gain through a variety of adaptations in response to weight loss. So in other words, if you lose weight, your body is trying to regain that weight. Or is it if you lose weight, you can maintain that weight? Is this a false statement? Give it a little bit, you know, true and false. Usually people are, assets will probably be flowing in a lot quicker. Okay, looks like we're all wrapped up. Okay, so we see the majority of individuals have voted true. And they would be correct. So over 80% of you voted true. Once obesity is established, the body does attempt to promote weight gain through a variety of adaptations. So we're going to talk about that a little bit more today. So, you know, why is it so difficult to maintain weight loss once obesity is established. So let's say you you've reduced your adiposity, you have lost some weight, your body doesn't necessarily understand the external environment as to what might be contributing to this weight loss. And so it's going to have a physiologic response to weight loss in the notion of changing your hormone levels, as well as adjusting your metabolism. So with respect to your hormone levels, what it's doing is reducing your fullness hormones, but increasing your hunger hormones. So what does that net effect, it's ultimately encouraging more energy intake, you know, to stabilize to prevent further weight loss. On the metabolism side of things, it's going to impact your rate of metabolism. So it's going to try and decrease the metabolism, again, to mitigate any of that weight loss that might be happening. Because it doesn't necessarily understand why this weight loss is occurring. So it's trying to, you know, lack for a better terminology, protect you. But the net effect of this is ultimately going to be that weight regain. So we've lost some weight, but our bodies combating it to allow us to regain that weight. Now, I'm gonna show you an example, from reality TV that many of you might be aware of already. But I think it really exemplifies what I'm talking about here, which we have termed metabolic adaptation in a real world setting. So have, you know, I can't remember when this was back out, I think it was around 1015 years ago, biggest loser competition. This was a reality show where individuals are putting like on a 30 week, really intensive weight loss competition. So they were given an intensive diet. So this was hypocaloric diet could have liquid diet components here, and very intense exercise. And so participants, on average, are around 150 kilograms at the start of this program, and so when we look at their resting metabolic rate, this is around 220 500 kilocalories per day. So this is just for maintenance purposes, they would require around 2500 kilocalories per day. Now, following the 30 weeks of intervention, we actually saw a very impressive, very significant weight loss reduction. So on average, these participants lost see almost 60 kilograms of their total body weight. So they're, they're not sitting around 90 kilos. So they came in at around 150. They're now sitting at around 90 kilograms. And in now that they're living in a smaller body size, we do see a reduction in their resting metabolic rate. So now there are around 2000 kilocalories per day for maintenance. Now this, the program's done, you might be asking yourself, if you were somebody that did watch it, was there ever a reunion episode of The Biggest Loser? Short answer is no, there wasn't. But there was a publication done. So some data investigation as to what happens to these participants after leaving the show. And so they looked at around 14 Out of the 16 participants were contacted six years after the show ended. And we looked at, you know, what the what their body weight was right now, as well as what their resting metabolic rate was. So I'm just gonna give you a couple of seconds to think, do we suspect that they maintained that weight loss, did they further lose weight, or do we have weight regain. And unfortunately, they saw around two thirds of the weight was regained six years out from this, from this TV show, so on average, individuals regain around 4040 kilograms of their total body weight. However, what was very unfortunate to see was that their resting metabolic rate did not go back up to that baseline level. So if you remember, when they were sitting at around 150 kilograms, total body weight, their resting metabolic rate was 2500 kilocalories per day, they lost the wait, they were living in a smaller body, their metabolic rate went down. Now that they're living in a larger body than they were, we may have suspected that their metabolic rate would have went up. In fact, it stayed down went down a little bit further, actually, than what it was before. And this is what we are calling metabolic adaptation, there is this physiologic response, your metabolism is being decreased? Ultimately, this is resulting in burning of less calories at rest, while feeling less full and more hungry when we talk about that hormonal component, all coupled into this. So I mentioned earlier, there are many paths that lead towards obesity, one of which is our biological component. How does our brain control appetite, control hunger? Well, it's done through three, three major centers. So the very first center is this homeostatic eating. So homeostatic eating is what we do to survive. This is what animals do humans do this is eating for hunger. All humans do this, as babies, we, you know, typically eat stop when they're full. That's the typical, let's say infant type style of eating. This is largely controlled by hormones like GLP ones, which increase satiety. So this suggests like, you know, that fullness aspect, and it's also regulated by ghrelin, which is a hunger hormone. So this is secreted by the stimulated to be secreted by the brain, ultimately, resulting in an increase in hunger to, you know, permit the body to consume more calories. But many of us probably sit more towards this right hand side, which is hedonic eating. This is eating for pleasure eating and a social type of interaction. This is largely regulated by things like dose dopamine, the open opioid and cannabinoid receptors in our brain. This controls the liking the wanting of food, what makes you to pick one dish over another dish, one dessert over another dessert. That's all largely regulated by hedonic eating. But then deciding to eat is controlled by our prefrontal cortex. This is the sustainable behaviors in which we control our eating. And you can imagine that anywhere along this line, if there is a disruption it can all ultimately impact appetite regulation. So overall, what I want to kind of conclude from this very first part of what I've been discussing is that obesity is not simply due to an individual's choice or lack of willpower. There are many paths that can lead towards obesity, and it's really up to the healthcare professional with their patient, and understanding, you know, what is the root cause of obesity in particular person's life and addressing it from there. Okay, so now we're going to move on to looking at clinical practice guidelines. So I'm going to briefly go over this. So you can kind of think of these as blueprints that healthcare professionals use in the management of obesity in their clinic, Canada has some phenomenal clinical practice healthcare, clinical practice guidelines, they've been outright adopted by a couple of countries like Ireland, Chile, purely to be used as their own national guidelines for the management of obesity. And there's a number of chapters in it, you can actually go online and see the entire clinical practice guidelines, there's one meant for healthcare professionals, there's one meant for patients. And one of the components is diagnosing obesity. And there's a number of different steps to go through here ensuring that the patient is part of that decision making process, making sure we're using appropriate measurements. But I've bolded here addressing the root cause of obesity, because that's going to be very dependent. It's going to be very important in deciding you know what type of management will be done and moving forward. There's a whole chapter discussing weight bias and weight stigma and obesity. So you can pick up weight bias. Again, it's as any bias it's these negative attitudes and assumptions and judgments that society might have towards people living with obesity, and stigma is harmful social stereotypes. We do know that 40% of adults have reported you know, bias and stigma amongst family, employers, HR professionals health care, as well as other people living with obesity. And the consequences of this is ultimately an increase in morbidity and mortality independent of BMI. It impacts physical well being psychological and psychosocial well being and maybe even the want to access certain health care. Within the clinical practice guidelines, it does break it up into into all the types of interventions that are available for patients. One such intervention being medical nutrition, therapy, so this is what you will have formerly uses the word diets. So diets applied very short term very fat like fad, like interventions, while nutritional intervention is a way of life healthier eating, what are the actual impacts of healthier eating, maybe it's a protein rich diet, maybe it's that Mediterranean diet. So there's a whole chapter dedicated to it, I'm not going over it today, as well as one dedicated towards physical activity. So another type of lifestyle intervention, this is what you again, would have, you are familiar with the term exercise, physical activity, is what you are capable of doing. Because when we talk about exercise, not everybody can do maybe that 150 minutes of moderate to high physical exercise per week, right. But some physical activity is better than no physical activity. And so, these are two components that are in the clinical practice guidelines, and there but to discuss the pillars of obesity management, because these lifestyle recommendations that I just talked about, we do know there is some weight loss associated with it around three to 5%. However, maintenance of that weight loss tends to be a bit of an issue in the long run. But there are pillars or these tools that patients have available to them that might improve the outcomes of management of obesity. These include behavioral interventions, like cognitive behavioral therapy, maybe counseling, pharmacotherapy, There are currently four approved medications in Canada with respect to obesity management, listed them here. I'm going to be talking about it shortly as well. And then, for certain patients, it might be appropriate to suggest bariatric surgeries, which again, we know also results in quite significant weight loss that can be life changing. But purpose of today's talk is to really focus in on that pharmacotherapy. So how does a healthcare professional alongside their patient kind of decide it is an appropriate time to introduce pharmacotherapy in the management of of obesity. So, in the clinical practice guidelines, there's a statement in there that says when health behavior change alone, so this is lifestyle intervention so that physical activity nutritional intervention has been ineffective, insufficient or without sustained benefit. It may be an appropriate time to discuss, you know, what type of pharmacotherapy interventions can be used. And there's like I mentioned four different agents that are currently available so orlistat, which on average sees around 3% weight loss at the one year mark. Now trek zone pro prion, which is around 6% weight loss. At the one year mark brand name here is Contrave. liraglutide, which sees around 8% weight loss at the one year mark brand name six Senda. And then semaglutide 2.4 milligrams C's around on average 15% weight loss at the one year mark, brand name, here Wegovy. So I've delineated you know what the effect is on weight loss. I just kind of want to remind you here that we talked about what is clinically significant or meaningful weight loss and how does it impact health. And we know that at least 5% Is, is life changing, it can impact many different states of our health by going upwards of 15, even 20% weight loss, we see further improvements in our health. And so with that, I'd like to focus the rest of our time now on semaglutide 2.4 milligrams otherwise known as Wegovy. So 

Rami Halabi  00:31:46 

I'm going to talk about the product monograph and the Health Canada indication shortly. But before I get into that, I just want to show you the how extensively studied semaglutide has been in people living with obesity. So the STEP program, which stands for semaglutide treatment affecting people with obesity is quite a large clinical trial program. In pink on the left, these are our 15 completed trials, of which many have publications already available through many of the research journals. But then we also have a number of trials that are currently ongoing, showcased here on the right stemming from younger populations being studied, as well as you know, very specific like to mainland China, Taiwan, and Taiwan, as well as looking at a US employer type trial. Within Canada, Wegovy's Health Canada, and indication is actually done in adjunct to a reduced calorie diet and increase in physical activity for chronic weight management. This is very important because summer 2.4 Wegovy has been studied in adjunct to a 500 kilo Cal restriction as well as an increase in physical activity. So all of those clinical trials that I mentioned before, use that as a baseline. So whether you are in the semaglutide arm for treatment, or you are in a placebo arm, you are always being counseled on that lifestyle component. And so Health Canada indication reflects that. It's indicated for adult patients with a body mass index of at least 30 or 27. With a weight related comorbidity, this can include hypertension, type two diabetes, dyslipidemia, or obstructive sleep apnea. Just to know Health Canada has also given approval for pediatric patients aged 12. and above. In the pediatric population. They do not use BMI criteria in the same context, it's actually done in percentiles. So the individuals have to be in the 95th percentile or greater for their age and six. Again, this is all an adjunct to a reduced calorie diet as well as an increase in physical activity. So how does we go we work? Well, we know it actually has targeted effects on the brain to regulate appetite. So I talked about GLP ones earlier as being one of those hormones that are involved in homeostatic static eating. So this is that eating for hunger and GLP ones are involved in satiety, which is very similar to fullness or you know that feeling of fullness semaglutide or Wegovy is a GLP one analogs so it mimics the effects of GLP one and it targets areas. response in the in the brain responsible for appetite regulation. So ultimately, we We have a decrease in energy intake. So, you know, this could be consumption of calories, a decrease in hunger. Ultimately, this is increasing appetite regulation. So increasing satiety or increasing that fullness aspect. And we have a reduction in body weight at the end. Now, I want to walk you through how we know obesity is a chronic disease like, again, this this disease state has been extensively studied in the literature. But, you know, part of the requirements with clinical trials is to really show you know what the importance is of using a pharmacological intervention in the long term. So one of these clinical trials that I mentioned earlier, it's this is part of those 15 that were completed. So here I'm showing you a trial called Step four, otherwise otherwise known as the withdrawal trial. So in this study, all participants were given semaglutide 2.4 milligrams, so they were all on Wigo V for the very first 20 weeks, 20 weeks, because that's how long it takes to get to that maximal dose titration. At week, 20, a third of these individuals were had the medication removed, however, lifestyle intervention remained. So all of these participants are still coached about that 500 kilo Cal restriction in energy intake, as well as that increase in physical activity, up to 150 minutes a week. Now, 1/3 were had the medication removed, but then the two thirds continue taking that medication. So at week 20, we see on average, we're losing everybody's losing around 11% of their total body weight. What do you think happens once medications removed? So I know none of you can chat with me right now. So I'm just gonna give you a couple seconds to think about it. Knowing that obesity is a chronic and relapsing disease, so think about those other disease states that you're familiar with, like type two diabetes, hypertension, what happens when medication is removed, with somebody's glycemic state their blood pressure. While we know there's, well, unfortunately, what we see is a rebounding of their total body weight. So here in dark pink are those individuals that remained on treatment. So week 20, they continued taking semaglutide 2.4 milligrams up to week 68. And so we see on average, around 17%, total body weight loss, however, those that at week 20, that were on semaglutide, but then the medication was removed. However, this is still on top of lifestyle intervention, we see their weight is rebounding. So that's delineated here in gray. And we see on average, a 7%. weight regain over the next 48 weeks. And so at the very end of 68 weeks, we see 17% Weight Loss of those that remained on treatment, while a net 5% Weight Loss of those that were on treatment at the very beginning, and then it was removed. So ultimately, what this again, really describes quite well is that obesity is a chronic and relapsing and progressive disease. And so removing that one of those interventions, ultimately results in that rebounding effect. So I brought the slide up a couple of times, but I think it's just so valuable and so important that we recognize that clinically significant weight loss of at least 5% provides meaningful health improvements to the patient, and upwards of 20%. You know, we see even further improvements in conditions like heart failure, or type two diabetes. And in our, in all the semaglutide 2.4 milligram trials are would go the trials, categorical weight loss is something that is captured. So this is, you know, talking about what percentage of individuals lose at least 5% of their body weight, we know that it's almost 90% of individuals will lose at least 5%. So that clinically significant, or clinically meaningful weight loss, that over half of individuals, so you know, 64% of individuals will lose at least 15% of their total body weight. So again, we're looking in this little quadrant here. And that 40 around 40%, or upwards of 40% of participants may lose greater than 20% of their total body weight. Again, we're hitting those categorical weight loss where we know that There is improvement in multiple types of health conditions. And I've just really been focusing a lot on the weight loss component. And that's because in all the clinical trials, Wegovy is prime, its primary endpoint is always looking at percent weight loss. However, many of the secondary endpoints in these clinical trials looks at a look at a number of different parameters, individuals that move from pre diabetes to normal glycemia. So we see, you know, over 84% of individuals in some of these trials, considering their living with pre diabetes upon beginning the trial, we see many of them switch over to a normal glycemic status. At the end of these trials, we also see improvements in systolic and diastolic blood pressure. So again, this is a secondary endpoint of Wigo V, as well as dyslipidemia. So if we look at fasting lipid levels, we see generally, we do typically see greater reductions in individuals that are on Wigo V versus those that are on placebo. Just a reminder, placebos, not nothing it is still lifestyle intervention. 

Rami Halabi  00:41:20 

And semaglutide itself as a molecule, which is the main medicine, active ingredient in Wigo V has a very extensive and well established safety profile from a number of clinical trials as well as real world experience. We do know that the most common side effect with Wigo v is going to be gastrointestinal related adverse events. Generally these are mild to moderate and severity, generally transient typically seen during that dose escalation phase. So up until those 20 weeks when we keep titrating, our dose higher, we tend to see the largest influx of these adverse events, the safety and tolerability of semaglutide has been established in over 33 clinical trials. Over 20,000 people testing it in multiple dosage strengths for individuals living with obesity, with type two diabetes, with metabolic dysfunction associated Seattle hepatitis, which many of you might have been familiar with the term Nash, it has its underwent a renaming as of last year to mash. And we do know that you know, there's over 1.6 million patients currently worldwide being treated with some Allah tied molecule for other conditions be a type two diabetes. And so the safety profile and efficacy profile has been well established on a clinical trial and a real world basis. So to conclude on the front of Wigo V. It's the first and the only ones weekly glucagon like peptide one. So GLP, one receptor agonist, like I mentioned, in the medic for our endogenous GLP, one for weight management. On average, we see upwards of seven up to 17% weight loss across the phase three a clinical trial program, we see meaningful improvements in cardio metabolic risk factors, be it blood pressure or faster lipid states, and there's a well established safety and tolerability profile overall. And because I know this will be of interest to the group that is listening in today. I do have two slides here talking a little bit about you know, what are the patient's supports that are available for an individual that is prescribed would go V. We do have a patient support program called with OB care. It's available via phone or video. This is live educators support so it's one on one support for both like for be it for device training, medication support, cognitive behavioral support, might be discussing side effect profiles. There are digital resources as well available for patients that are prescribed would go V and a reimbursement navigation tool. So for patients with a private plan, a reimbursement specialist kind of investigates on their behalf, whether they might be eligible for coverage of Adobe and for many of you you may already have six Sen listed on your plan. So six Senda is liraglutide three milligrams, one of the four approved obesity pharmacotherapies in Canada you know the Prime Day between Wegovy and six ENDA, there there's price parity here in fact, Wegovy's around 2.6% ci Per then sucks sender. And this is primarily due to the needle being included with the pen. So, again, I'm happy to discuss any questions you have about what that dosing paradigm looks like. I just wanted to be cognizant of time that to make sure I delivered more on the data side of things, but happy to talk about what the device looks like as well. So on average, there is that price parity, however we go we is 2.2 point 6%, cheaper, or less expensive than 600. And just to finally summarize, hopefully, what you're taking away from this webinar here today is that, you know, the prevalence of obesity in adults has absolutely increased within the Canadian landscape. And with that bias and stigma have increased, which we know lead to morbidity and mortality. And that obesity is not just a measure of size, it's, it's not, we're really looking at it as a chronic disease. It's prevalent, it's complex, it's progressive, it's a relapsing disease, and it impairs our health. And with the clinical practice guidelines, it is a very patient centric approach. Like I mentioned, these guidelines are available for patients and healthcare professionals alike, ensuring that there is that unity about what the goals could be for that patient, and how to achieve those goals. It's based, it's completely evidence based management in his clinical practice guidelines, and it moves well beyond that concept of eat less and move more. And at the end of the day, this clinical practice guideline gives you know, the options for the patients be it that medical nutrition therapy, physical activity, intervention, psychological intervention, so those behavioral, that behavioral pillar, pharmacotherapy as well as surgery. And with that, I would like to thank everybody here today, happy to field any questions. If there are any additional comments that, you know, we don't get to today, my colleague, Dan Ekstrand, and who is on the line with us, can can definitely support after this call is done. 

Manal Ali  00:47:27 

Thanks so much, Rami. So there are a few questions from the audience. So I'll just get right into those in the interest of time. Could you comment on the impact of weight cycling with health there is as a result of patients living with obesity, trying different weight loss interventions? 

Rami Halabi  00:47:46 

Yeah, this is a fantastic question. And I mean, this is a question that even our health care providers are asking, we actually don't know directly what the impact is of weight cycling. You know, this has been coming up a lot, because we talked about access, like equitable access to interventions, some individuals might be managing their obesity for quite some time, and then, unfortunately, due to unforeseen circumstances, may not have access to that management anymore. And so we see that weight cycling happening, we do know, you know, increasing adiposity have, of course, impacts our health, does that yo yoing up and down impact our health. I don't have any evidence, or any data at this current point in time to tell you that it's more or less or equivalent detrimental to just increasing adiposity. So great question. Unfortunately, I don't have a concrete answer for you. 

Manal Ali  00:48:45 

Got it. Okay. And the next question is, was the step four trial? Double blinded? Like did the one out of three patients who came up with a treatment No, they were off treatment, or did they continue to get the placebo? 

Rami Halabi  00:49:00 

Yeah, so it is a great question as well. This is a double blinded trial. So this, these individuals were just like the the pen itself for both placebo injections, or the summer 2.4 injection will look identical. So as far as the patient's know, they're still taking some sort of treatment. They don't know what that is. So it's completely blinded to them. So they're still doing that weekly injection, but those that are switched to placebo, it's a placebo injection. 

Manal Ali  00:49:30 

Got it? And another question is, since it looks like you'd have to stay on it for life, what do studies show about any adverse results of longtime use? 

Rami Halabi  00:49:42 

Oh, fantastic question. So with respect to the trials, I showed you, those 15 completed trials, the longest one to date would be the Select cardiovascular outcome trial. It's upwards of like, you know, between four and five years participants in that trial We're on Soma 2.4. This was not an obesity focused trial is actually a cardiovascular outcome trial looking at the reduction in major adverse cardiovascular events of which we go, we showed a 20% reduction. Now, in this trial, I believe your question was like, you know, any adverse events, there was no new safety signal. So again, we typically saw those GI or hepatobiliary disorders that pop up in all of the obesity trials that are shorter and durations appeared again, in that 440 month or four to five year trial called select. So no news to the safety signals were uncovered. 

Manal Ali  00:50:44 

And we have a couple of like costs based questions next, will all insurance insurers be covering Wegovy under their plans? 

Rami Halabi  00:50:54 

Oh, this, I might have to ask my colleague, Dan, to comment. 

Dan Ekstrand  00:51:02 

What I can attest to is we have sent product submissions to every private payer, and every private payer will have a slightly different review process. So that has been initiated, we have some early positive signals sent some private payers have already gone through the submissions and made access available. But again, that that's something that is somewhat beyond our control, there is a very robust product package that is sent out to all private payers, and every private payer will have a slightly different review process, but that has been initiated. And that process has begun.  

Manal Ali  00:51:36 

Okay, so would you know what the annual costs? Are? Wegovy now then, Dan. 

Dan Ekstrand  00:51:43 

It this particular time, please bear in mind that we're looking at you saw the the costing that was presented at the end of the presentation. This is somewhat dependent upon a person's response rates. So one pen typically Rami, perhaps you can speak to that the one pen How long does that typically last? For someone that has been treated for their obesity condition? 

Rami Halabi  00:52:05 

Yeah, so each pen is formulated with four doses. So with respect to actual titration is we gobies taken on a weekly basis. So if you're at 2.4 milligram dose, you are taking 2.4 milligrams once a week, that Pan last year for four weeks. 

Dan Ekstrand  00:52:28 

Okay, so what I would also say is that if you compare it to existing therapies, and if we take a look at it from an efficacy parameter, I would suggest that liraglutide currently would be the most efficacious based upon data. If you take a look at it from that benchmark and Laura Agha tied molecule is currently available and has been available in Canada for several years. As Rami alluded to the cost of treatment and maintenance for the Gobi would be on par with what is currently or what was currently best in class in terms of obesity efficacy, so we will be comparable to liraglutide which has been approved in Canada for the treatment of obesity for several years.  

Manal Ali  00:53:09 

Okay, and as we go be commercially available now in Canada, like how is the consumer availability of purchasing it from pharmacies? 

Dan Ekstrand  00:53:18 

Yes, so it is currently commercially available, it is available right now in wholesalers as well as at pharmacy. 

Manal Ali  00:53:26 

Awesome. And so another question was, why would you have to stay on with OB for life? If studies show the body is able to adapt to its new weight? Could it not adapt back to a normal weight after Wegovy? 

Rami Halabi  00:53:43 

Okay, good question. So, studies have shown that the body adapts in the other direction that it tries to promote weight regain, I believe what you might be alluding to is does the body have a new set point, let's say if you've been living in a, you've reduced your total body weight by X percentage is the body now adapting to this smaller size. And we actually don't know. There's a lot of unknowns, I guess to say in this area, even in the bariatric surgery place we do know, many individuals may relapse post bariatric surgery, which has, you know, by and large has shown the greatest efficacy on weight loss that maybe four or five years out, they ultimately have weight regain. And so this idea of you know, does the body adapt to the new body size? The Evers evidence doesn't lean in that direction. But we also just don't have the data to show that. So like I said mentioned earlier, this is a chronic disease, and it's relapsing and it's progressive. And so like your treat hypertension, it's it's in that same type of paradigm. 

Manal Ali  00:54:54 

Got it and how long can you stay on will go up? 

Rami Halabi  00:54:59 

Yeah, again, Unlike it's we've studied, studied it up until five years in a clinical trial basis, but if we're talking about real world evidence, while there are many individuals that have been on this magnetite for quite some time since it was launched for type two diabetes, this is for chronic use. So again, once somebody is taking the medication, it's it's meant to be used for that lifelong management of the disease. 

Manal Ali  00:55:31 

Okay, and another question is, what is the cardiovascular safety of with OB? 

Rami Halabi  00:55:39 

Yes, so with respect to cardiovascular safety, it's, we've always looked at cardiovascular or cardio metabolic factors as secondary endpoints and all of our obesity focus trials. So this would be looking at fasting lipids, see serum insulin, blood pressure, as well. And we do generally see improvements across the board, depending on what type of study are looking at. They're of different magnitudes. However, there is a dedicated cardiovascular outcome trial that was completed last year. This is the Select cardiovascular outcome trial, where the purpose of it was to see if on top of standard of care, so individuals that had previous heart attack or stroke or peripheral arterial disease, did they have a reduction in their any future events? And and in that study, which lasted up to five years, they did find that Wegovy resulted or summit 2.4 resulted in a 20% reduction of risk reduction in development and having another episode in these patients. 

Manal Ali  00:56:47 

Got it? And another question is how is Wegovy different from ozempic? 

Rami Halabi  00:56:54 

So the indications are different between the two. Both of them use the active ingredient semaglutide. However, ozempic is indicated for type two diabetes, whilst Wegovy is indicated for people living with obesity, or obesity with a weight related comorbidity. 

Manal Ali  00:57:15 

And do you know if life insurance companies are covering Wegovy and the criteria they use for coverage? 

Dan Ekstrand  00:57:25 

Again, I can address that every private payer will go through their own review process. So that has been initiated. And again, most private payers as well were trim the criteria that they deemed to be appropriate. As I shared previous, we have had some early signals that many private payers that had provided access to existing OBC therapies have done the same for what goby? So we're hoping that that will continue. 

Manal Ali  00:57:52 

And are you foreseeing any supply issues, which presumably caused the delay in marketing of Wigo V in Canada? 

Dan Ekstrand  00:57:59 

Actually, we want to take a very measured and appropriate response to the introduction and the availability of a goalie as such, we have taken a very staggered approach. And so we're hopeful that this more governed approach will lead to and mitigate the risks of any supply issues. So we are very conscious around the timing and availability will go away to ensure that if we have people that have been initiated on therapy, that they'll be able to continue on through their course of treatment. 

Manal Ali  00:58:29 

Okay, thank you, and how does diet and exercise fit into the clinical studies of obesity and pharmacotherapy? 

Rami Halabi  00:58:40 

Yeah, so ont with respect to any of these obesity focused clinical trials, it as a baseline, so whether participants are randomized to the drug itself, so semma, 2.4, or to placebo, they are all encouraged, are given the same type of counseling, which is reduction of caloric intake by 500 kilo calories a day, as well as an increase in physical activity up to 150 minutes a week. And so that's the baseline lifestyle intervention for your typical obesity trial. 

Manal Ali  00:59:19 

And are you able to comment that question is are you able to comment on cases of improved fertility on semaglutide for long term use and its safety on the fetus. 

Rami Halabi  00:59:32 

So, in the product monograph, it is suggested that you know, if an individual is on Wegovy and is planning on getting pregnant that they do stop taking Wegovy at least two months prior. This is because we do not study the exposure of this type of product and individuals who are pregnant or planning to get pregnant or breastfeeding. So this is not, not within our product monograph. So we do not know, establish safety or efficacy on that side of things. So again, stop if you're planning on getting pregnant with respect to improve fertility. I believe I know where that question is coming from because it's been up in the media quite some for quite some time. We do know and I mentioned it earlier that obesity is linked to a number of other chronic health conditions, one of them being polycystic ovarian syndrome, so PCOS and that it's a metabolically linked disease. And so, management of obesity may improve other metabolic conditions. And so there could be this improvement. But again, there's no dedicated studies here, not part of our product monograph. Yeah. So not part of our product monograph, not an indication for the management or improvement of fertility. 

Manal Ali  01:01:03 

Okay, and I'm sorry, even though we do have a couple more questions, that's all the time we have today. So thank you so much Rami for sharing your insight and vast expertise, and to everyone in the audience for joining us today. On behalf of Benefit and Pensions Monitor. I want to thank our sponsor, Novo Nordisk Canada for their hard work and support leading up to today's webinar. Have a wonderful rest of the day. Thank you so much. 

Rami Halabi  01:01:27 

Thank you, everyone.