Conquer Your Weight

Dr. Sarah Stombaugh: Before we get into the episode, I am thrilled to announce we are launching an online course, The GLP Guide. The GLP guide is a must have resource for patients who have been prescribed any of the GLP medications such as Wegovy, Ozempic, semaglutide, Zepbound, Mounjaro, tirzepatide, Saxenda, liraglutide. There are a lot of them and this course is available for anyone to purchase. We often hear from people who haven't been given much information about their GLP medications. No one has told them how to handle side effects, what nutrition recommendations they should follow, or what to expect in the longterm. And it can be really intimidating and simply frustrating to feel like you're alone in your weight loss journey. With the GLP guide, you'll get access to all of the answers to the most common questions for patients using GLP medications, not sure how to use your pen, struggling with nausea, wondering how to travel with your medications. We've got you covered for only $97 for one year access. This is an opportunity you do not want to miss. The course is launching on October 1st. For more information and to sign up, please visit www.sarahstombaughmd.com/glp. You don't have to be on this journey alone. We are here to guide you. And now for today's episode. This is Dr. Sarah Stombaugh, and you are listening to the Conquer Your Weight Podcast. Announcer: Welcome to the Conquer Your Weight Podcast, where you will learn to understand your mind and body so you can achieve long-term weight loss. Here's your host, obesity medicine physician and life coach, Dr. Sarah Stambaugh. Dr. Sarah Stombaugh: Hello everyone and welcome to this week's episode. We are going to be talking about the GLP medications, which is the best one, maybe which is the best one for you. We are going to go through some of the data and I'm actually going to reference some of the clinical trials and then talk about when I have a patient in front of me, how we are making the decision of which medication to use. And then we'll talk a little bit too about what are some of the things coming down the pike because there are actually some new GLP medications that or other GLP sort of plus medications that we expect to come to market over the next one to two years, which is really pretty exciting. So before we dive in, though, what I would love to ask you is if this episode or another one, if it really spoke to you, and you felt like, oh, my gosh, this was just amazing content and answered a question that I have had for a long time, or I know people in my life have been thinking about this as well. And you know, so and so if someone sort of pops into your mind, if they would really be from hearing this, I would love to invite you to share that podcast episode with them. I love hearing stories of people who shared the podcast with a friend, with a family member, something that really resonated, maybe either because of a specific medical condition that they've been dealing with, or maybe a conversation that the two of you had at some point and realizing, oh gosh, I think he or she would really benefit from hearing Dr. Stombaugh's podcast. If you could share your favorite podcast episode with someone, I would just really appreciate that getting into the ears of even more people. I love being able to support people with their weight loss journey and especially their mindset as they're working through that. So thank you so much for sharing that those episodes. I really, really appreciate it. So today we are going to get into the data, which is the best GLP medication for me? How do I decide which medication should I take? So today we're going to be using primarily brand names for the obesity versions of medication. So we've talked about this a little bit before, but when we're talking about semaglutide products, those are typically the Wegovy medication and the Ozempic medication. So when you hear Ozempic, Ozempic, you hear Wegovy, or you hear semaglutide, those are all referring to the same medication. Now, semaglutide is the generic name of the medication, and it has two different brands. It's branded as Ozempic for the treatment of type 2 diabetes. It is also branded as Wegovy for the treatment of obesity. Of course, it also has been, over the last couple of years, compounded very commonly, so people are also used to calling it by the word semaglutide, depending on how they've been getting it. But today, for the ease of simplicity, I'm going to refer to it as a Wegovy primarily. Similarly, as we talk about the tirzepatide products, Zepbound and Mounjaro are both tirzepatide medications. So tirzepatide being the generic name of that medication, Mounjaro being the version that is branded for the treatment of type 2 diabetes, then Zepbound being the version that's branded for the treatment of obesity, and tirzepatide, again, a lot of times referring to the compounded medication very recently, but really it's just the generic name of that medication. So today I'm going to try to use Zepbound as we're discussing you know, discussing and referring to that medication. Then I'm also going to be talking about a medication, Saxenda or liraglutide. This is one that we don't talk about as often, but this was actually the very first GLP receptor agonist that was approved for the treatment of obesity. All of these GLP receptor agonists have been around for a while, just about 20 years now. When we look at the earliest FDA approved GLP products, the very first one was Byetta. The early products were all for the treatment of type two diabetes. And then over the last couple of years, really last decade now, we've seen evolution as they've been approved also for the treatment of obesity. So there was a medication called liraglutide. That is the generic name of medication that was first FDA approved as Victoza for the treatment of type 2 diabetes. And then a couple of years later was branded as Saxenda for the treatment of obesity. Now, one of the main things about Saxenda medication, and I guess we're going to dive into it. This is a daily GLP receptor agonist. And so when you compare that to Wegovy or Zepbound, which are once per week medications, who wouldn't want to take a medication weekly if that's an option rather than having to take it every day? Also, when we look at the time that Saxenda got FDA approved in, I think it was 2014, the early 20 teens, the medication was also getting approved around the same time as two other medications, Contrave and Qsymia. Those are both pill medications. We're not going to talk about them terribly much today, but when you look at the effect of Saxenda compared to Contrave, compared to Qsymia, they're all moderately effective on the order of creating six to 9% total body weight loss on average, but there was nothing about the Saxenda medication that really stood up above and beyond those other medications. So everybody was like, why would I take a pill when, or why would I take an injection when I could just take a pill? Also from an insurance coverage standpoint, it was typically preferred to look at pill versions of medications, those Contrave or Qsymia medications. And so it just never really took off in the same way, but I feel like there's been a bit of a resurgence, maybe just in my own mind, I've been a little excited about the Saxenda of medication and we'll talk about that, but a little bit of a resurgence of the use of Saxenda of medication as we've seen the popularity of the other GLP receptors rise. So we are going to talk about that one as well. So let's get into it. What are the differences between these medications when you're making a decision about why should I use Wegovy? Why should I use Zepbound? Maybe I'm even thinking about a medication like Saxenda, for example. What are the factors that I'm going to use to decide if I should utilize which of these medications? So Wegovy was, when we look at the weekly versions, Wegovy has been around a little bit longer compared to the Zepbound medication. Wegovy was first branded for the treatment of diabetes as Ozempic and then secondarily branded for the treatment of obesity. So Wegovy is FDA approved for the treatment of overweight and obesity. So for patients who have a BMI of 30 or higher or patients who have a BMI of 27 or higher with the weight-related comorbidity. So these are conditions like high blood pressure, high cholesterol, prediabetes, polycystic ovarian syndrome, osteoarthritis, fatty liver, other conditions that are known to be related to metabolic disorder. If someone has that BMI 27, 28, 29 with a comorbid condition, they do technically meet the FDA approved criteria for this medication. So that is one indication for which the Wegovy medication is covered. Last year in 2024, Wegovy got a secondary indication for the treatment of cardiovascular disease. So Wegovy was studied in the treatment of cardiovascular disease for patients who had a history of cardiovascular disease and looking at cardiovascular risk reduction for patients who had already had cardiovascular events. And so it did also get approved for that indication. So for patients who do have a BMI of 27 or higher with a history of cardiovascular disease, things like heart attacks, things like stroke, this is an approved indication for the medication as well. So at this time, I'm so hopeful that some listens to this episode many years from now, and they're like, what is she talking about? Wegovy is used for many different things, or maybe this episode's totally irrelevant because all of these other medications have come down the pike. But at this time, there's the weight reduction indication, and then there's the cardiovascular risk reduction indication. That does not mean that there'll be insurance coverage for those, and we're not going to get too in-depth into that in this episode, but those are the two FDA-approved indications for this medication. For the Zepbound medication, there are also two FDA approved indications, one being the treatment of overweight or obesity, exact same criteria as the Wegovy medication on that. And then also for the treatment of moderate to severe sleep apnea in adults with a patient or with a history of a BMI of 30 or higher. And so it has both the weight, the overweight and obesity indication, as well as the sleep apnea indication. And then the Saxenda medication only has an indication for the treatment of overweight or obesity. So if you are someone who falls into the category, at least at this time, of having sleep apnea and you're looking at getting coverage under that indication, you look at someone who has had a history of cardiovascular disease and we're looking at risk reduction, you may be able to get Wegovy under those indications. So those may be very specific reasons by which you're choosing one of the medications over the other. When we look at the studies of Wegovy, on average, the Wegovy study showed about 15% to total body weight loss over the course of 68 weeks. I believe that number is 15.6%. There were additional studies that were done where they looked at over the course of two years. So for patients who stayed on that medication for a longer period of time, those patients actually had a total weight reduction of 15.2% on average. There were studies where they compared Wegovy to liraglutide medication, so to the Saxenda medication. And what they saw in that group was that the semaglutide or the Wegovy arm had a reduction of 15.8% over 68 weeks versus 6.4% in the Saxenda arm of that study. And so really we're looking at about 15% on average over the course of a year or a little bit more than a year, really about a year and a quarter. Now, they also looked at this medication with other with other health conditions as well. So recently, there has been a study coming out that looks at the treatment of semaglutide products for patients with osteoarthritis. What they found in that trial was actually a 13.7% total body weight loss, but there was an improved functional score. So for patients, they were feeling better, they were having less pain, they were having better function. And the Wegovy medication is being studied in a lot of different health conditions. It's being studied in the treatment of certain dementias like Alzheimer's or in Parkinson's disease. It is also being studied in sleep apnea, being studied in addiction. So things like alcohol addiction or other drug use disorders. It's being studied for heart failure beyond just the cardiovascular indication. It's being studied in kidney disease as well as fatty liver disease. So there's a lot of indications that are currently it's being studied for, and we may see that those approvals come down the pike for this medication being used in those patient populations. One thing to point out also about the Wegovy medication is that it is FDA approved for ages 12 and older. So at this time, the Zepbound medication is only approved in adults 18 years of age or older, and Wegovy is approved in ages 12 and older. And actually, the Saxenda medication is also approved in ages 12 and older. So for patients who are adolescents who've been struggling with chronic obesity and are interested in using a GLP medication alongside a comprehensive approach to their weight loss journey, we're really looking at the Wegovy medication or the Saxenda medication as options for them. We may see over the next couple of years that there is also a Zepbound approval, but those studies are still underway. When we look at the effectiveness of the Zepbound medication, one of the things that's really interesting about the Zepbound medication was that they studied the 5 milligram, the 10 milligram, and the 15 milligram doses of it as treatment doses of the medication. When we compare that to Wegovy, everybody was started at a low dose of medication, 0.25 milligrams, and they were titrated up to 0.5 a month later, titrated to 1.0, a month later, titrated to 1.7, and a month later, ideally titrated to 2.4 milligrams. So the studies of the Wegovy medication are primarily looking at patients at the 2.4 milligram dose, or some of them, the maximum tolerated dose, which is 1.7 or 2.4 milligrams. But we're really driving patients to the top doses of that medication. So when we see that 15% total body weight loss, for example, we're looking at that at the at the maximum tolerated dose. So that 1.7 or primarily really the 2.4 milligram dose of that medication. One of the things that was really unique about the Zepbound trial was that they studied these three different treatment doses. So everybody started at 2.5 milligrams. Four weeks later, they were titrated to five milligrams. The group of patients stayed on the five milligram dose. The remainder titrated to 7.5 and ultimately to 10 milligrams. Another group of those stayed at the 10 milligrams, and then the remainder of the patients titrated to 12.5, and then ultimately 15 milligrams. So in the initial trial, SURMOUNT-1, they studied over the course of 72 weeks a placebo arm, so patients taking placebo or no medication, then the 5 milligram, the 10 milligram, and 15 milligram, and studied over the course of 72 weeks what were the average weight loss for those different groups. And what they found is patients taking the 5 milligram dose on average lost 15% total body patients taking the 10 milligram dose lost 19.5% total body weight and patients taking the 15 milligram dose lost 20.9% total body weight. Now we're talking about this as a GLP receptor agonist, but you've probably heard me say before the tirzepatide products Zepbound medication is a dual receptor agonist. So it targets both the GLP receptor as well as the GIP receptor. And so It is a more potent medication, but it is also a different medication. It's targeting those two receptors rather than targeting just the single GLP receptor. So when we look at the data, we're seeing 15, 19, 20% total body weight loss. They also, of course, have studied this medication in the treatment of sleep apnea. In the sleep apnea studies, they were looking at what was the reduction in AHI. So what was the reduction in apnea hypopnea index? And people saw profound improvement in their AHI, a reduction of 25 points on average, 29 points on average, depending on which of the trials we're looking at. And then also some patients had disease resolution. So people who had sleep apnea and actually saw that their sleep apnea, if they were using the Zepbound medication, actually went away and met criteria for disease resolution. In patients taking Zepbound alone, there was a reduction of 42% of patients had disease resolution. In patients who were using a CPAP therapy as well as the Zepbound medication, they had a 50.2% disease resolution rate. So really, really pretty profound. So when we're looking at head-to-head these medications and then comparing it to something like liraglutide, it's easy to see, you know, with Wegovy, we're talking about 15% on average. With Zepbound, we're talking about 15, maybe 20% on average. And when we compare that to the liraglutide data, initially looked at about 8% total body weight loss over the course of a 56-week study. But in further studies, we've seen everywhere from 6% to 9% reported. So really pretty modest weight loss, especially with when compared to the Wegovy and compared to the Zepbound medications. Now, Zepbound, I didn't mention yet, is being studied in other conditions as well. So of course, it has the overweight and obesity indication, has the sleep apnea indication. It is being studied in the treatment of heart failure. It's also being studied in liver disease, in cardiovascular risk, in chronic kidney disease, also being studied in plaque psoriasis and psoriatic arthritis. And then as I mentioned earlier, it is being studied in pediatric obesity but has not been has not been done yet. So with these, we're seeing a lot of data start to come out about the efficacy of these, not just for diabetes, not just for the weight indication, but across other health conditions as well. We see a lot of overlap between those health conditions. And so I think we'll see a point where these medications start to stack up different FDA approvals for different indications, which may help to drive the insurance coverage of these medications, because we have not just logically proven the benefit. But we've actually... with studies, with evidence proven, look at the benefit in these different health conditions. Now, myself or any other obesity medicine physician, or honestly, any physician who prescribes these medications will tell you that they see the benefit across other health conditions, but having the data to back that up is going to be required before we see FDA approvals for these medications. So for someone who is deciding, should I start the Saxenda, what are the reasons that you would choose these? So number one, if you have a specific indication for which the Wegovy or Zepbound is approved, it makes sense that you might be using it for that indication. So Wegovy, for example, has that FDA approval for cardiovascular risk reduction in patients with a history of primary cardiovascular disease. If you have that background, it may make sense that you're using Wegovy because you may be more likely to have insurance coverage for that medication. Similarly, for Zepbound, if you have a diagnosis of moderate to severe sleep apnea with a BMI of 30 or higher, it may make sense that you're pursuing the Zepbound medication. If you are an adolescent and looking for a medication, someone who is the ages of 12 to 17, the Wegovy or Saxenda medications may make sense. If you're someone who is very responsive to these medications and looking for something that is not as potent, it may make sense that you're looking at something like Saxenda. And also, as a daily injection has a shorter half-life, so may lend itself well to people who need to stop the medication for a reason and are looking to bridge the experience. So recently, I've talked to some people who are in the pre-pregnancy or pre-IVF journey where... You know, a lot of the weekly medications, we're talking about stopping six weeks or maybe even eight weeks in advance, depending on the medication. And don't take my advice on that. Make sure to talk to your own doctor about what that decision should look like. But the Saxenda medication, because it is once per day, If you're skipping doses, it's going to be out of your system even faster. And so it may make sense to use a medication like that for someone who knows that they're going to be stopping the medication for a period of time, for example. Now, when we look at the effectiveness of Wegovy versus Zepbound, Zepbound is... simply a better, stronger, more potent medication. On average, people had more significant weight loss. On average, they had less side effects in the clinical trials. When you compare the Wegovy side effect profile to the Zepbound side effect profile, people had less side effects on the Zepbound medication, had a lower discontinuation rate. And so overall, it is a stronger and more potent medication. So many people will choose the Zepbound medication for that reason. Now we have seen, especially with the popularity of compounding medication, there's been a lot of this happening, certainly both for semaglutide and tirzepatide, but sometimes that is influencing the decision for people as well in that depending on the amount of weight that they need to lose, sometimes choosing a less potent option may make sense if we're talking about someone who doesn't have as much weight to lose. So the person who doesn't have as significant a of wait to lose may be a better candidate for a still potent but less potent medication compared to Zepbound. So I do have a lot of patients for whom if they are not... looking to lose huge amounts of weight, that potentially the Wegovy medication is a really good fit that allows them to have that appetite suppression, have less food noise, feel more in control of the choices that they're making without feeling like it's too potent of a medication. But it's challenging because we're seeing, especially a couple of weeks ago, we had the episode talking about the insurance coverage of these medications. There's a lot of other factors that are playing into this as well, primarily do you have insurance coverage for these medications at all? And then especially as we're moving into the future, do you have insurance coverage for one over the other? And of course, that will drive our decisions in a pretty significant way. Now, I did want to spend a moment talking about the medications that are coming down the pike because there are a lot of them, a lot that are in the GLP space as well, and ones that may be really good options for certain patients. So one of the things that's presently being studied is semaglutide and So similar to Wegovy, but at a 7.2 milligram dose. So this is three times as much as the current maximum dose of semaglutide. And that is showing really promising results for the treatment of weight. So we may see that this gets either branded as just a higher dose of medication or maybe even at a separate name brand. I think we'll just start to see some higher doses potentially get branded. We're also seeing oral semaglutide be evaluated. Oral semaglutide already exists for the treatment of type 2 diabetes as a medication. It is also being studied in the OASIS trials for the treatment of obesity. They initially studied a 50 milligram dose, then studied a 25 milligram dose and finding pretty significant weight loss in the order of 15.1% and 14% at 68 weeks and 64 weeks respectively. And so the reality is when we're talking about a pill that you take, that is a phenomenal option compared to having to take an injectable, maybe more cost-effective. We haven't seen the Rybelsus pricing go down. I think honestly, because they just want to keep all patients who are using it for the weight into from using it. So we haven't seen the Rybelsus pricing go down. It's like $1,000 per month to pay for Rybelsus out of pocket. So it's actually cheaper to get the injectable semaglutide or injectable Wegovy products. But I think as we see the approval for the other indication that we may see the price of that come down, that's something we're expecting over the next couple of years. There's also another oral GLP medication that just announced their phase three clinical trial earlier this year called Orforglipron. Orforglipron is an oral GLP. It was studied initially in patients who had type 2 diabetes, and they saw an average of 7.9% total body weight loss over 40 weeks. They also saw a clinically significant reduction in hemoglobin A1c. Now, there are going to be a lot more ongoing trials about that medication in that it was initially studied in patients with diabetes. It will also be studied in patients who do not have type 2 diabetes and also for longer periods of time. So at the 40-week mark, while, you know, 7.9% does not sound that impressive. Patients had not yet plateaued in their weight loss journey, so they were still losing weight. So it's anticipated that if that trial continues for a longer period of time and in working with patients with obesity, but without diabetes, that we may see more significant weight loss because that's what we've seen in other clinical trials. Like when we compare weight loss in Ozempic versus Wegovy, Mounjaro versus Zepbound, the weight loss, those medications are the exact same. You're just talking about a different patient population. And so the weight loss tends to be lower in patients with type 2 diabetes compared to patients without. Now, again, these are very generalized statements. I've had patients with type 2 diabetes who've done phenomenal on these medications. I've also had patients without diabetes who have not had significant results on these medications. And so really, we're just speaking in generalizations, but really promising data about another oral GLP medication. And whether that's daily, whether that's weekly. There's a medication called Retatrutide that has finished up phase two clinical trials and is phase three clinical trials right now. That is a triple receptor agonist that will target GLP, GIP, as well as glucagon. On average, that was showing 24% total body weight loss over 48 weeks. So very promising data on that. Stay tuned because I think we'll see even more exciting news as they study that for longer periods of time and in more larger groups of patients. Additionally, there's a medication called CagriSema, which is a combination of two medications that is also in phase three clinical trials, presently being studied in the treatment of type two diabetes, but also in the treatment of obesity and showing really promising results. Even in the patient group with diabetes, there was an average of 15.7% total body weight loss over 68 weeks. And so I share that to say, we have a lot of things being studied. A lot of things that have wrapped up their phase two clinical trials are actively in phase clinical trials, which is the last phase before we're looking at FDA approval submissions. And so I'm really hopeful that by the end of 2025, certainly into 2026, we're starting to see some of these new medications come down the pike, as well as approvals for other indications for the Wegovy or the Zepbound medication. And lots of good options out there. It can be really challenging to know, is there something specific about me that would make one of these medications better compared to another? another one. Working with an obesity medicine physician is absolutely the best way to have that conversation. So if you're interested in learning more about an obesity medicine physician, finding one in your area, the best resource is the ABOM, the American Board of Obesity Medicine. You can look up physicians who are in your area who have been certified in obesity medicine. That can be a phenomenal resource. If you're in Charlottesville, Virginia, where I see patients in person or throughout the states of Illinois, Tennessee, or Virginia, I would love to see you by telemedicine in my practice to help support you through these questions and help support you in your weight loss goals. Thank you so much for joining us in today’s episode. We’ll see you all next time. Bye-bye.