Robert Kushner, MD 00:00:00 This is just the beginning of really understanding how to use these medications, how to combine them, how to administer them. And I suspect, even more effective medication, not only for weight loss, but also regarding improved health.

Keith Reynolds 00:00:20 Welcome to Off the Chart, a Business of Medicine podcast featuring lively and informative conversations with healthcare experts, opinion leaders and practicing physicians about the challenges facing doctors in medical practices. I'm your host, Keith Reynolds, and on this episode, we're featuring a conversation between Medical Economics senior editor Richard Payerchin and Doctor Robert Kushner, a professor of medicine and medical education at Northwestern University. They're talking about the latest advancements in treating obesity and how physicians should approach the drugs, making a splash across the industry.

Richard Payerchin 00:00:55 I'm Richard Payerchin, reporting for Medical economics. With me today is Doctor Robert Kushner. He was the longtime director of the center for Lifestyle Medicine, and is a current professor of medicine and medical education at Northwestern University. Doctor Kushner, thank you for joining us today

Robert Kushner, MD 00:01:12 Richard, it's my pleasure.

Richard Payerchin 00:01:15 There's a lot to talk about with the new, new drugs that are out there regarding obesity, weight loss and diabetes. And I'll tell you what, I wanted to start with something based on a blog entry that you had published on your website, and that was regarding a talk that you gave in August to preventive cardiologists. And you said that the room was packed with physicians who want to learn more. What is the current status of doctors who are out there, especially primary care physicians who are out there? They're in their offices every day seeing patients. They're getting a lot of questions. I'm sure they're seeing a lot of the studies. Have they been quick to adopt these type medicines. Are they slow to react or respond? What's happening out there to the actual physicians?

Robert Kushner, MD 00:02:02 Yeah. Well, you're right, Richard. clinicians are increasing their awareness of these medications, both because they've been really flooding the literature with New England, with, New England Journal of Medicine and Lancet type articles, but also patients are making appointments to see them, really for the first time to talk about weight management.

Robert Kushner, MD 00:02:23 And are they a candidate for these medications? It's not just the primary care professionals. It's also specialists, in cardiology, in ob gyn, in endocrinology, even orthopedics, because these medications have really been a game changer regarding what we can expect regarding not only the amount of weight loss people are achieving, far superior than any medications before that. But I think, even more importantly, is improving the health of the individual. Improving blood pressure? blood cholesterol of blood sugar, reducing the development of a second. Heart attack. You've already had one. Improving fatty liver disease. All these complications of comorbidities. Individuals living with obesity experience. These medications are starting to help those as well as just weight loss.

Richard Payerchin 00:03:19 And doctor, I think that you've been pretty clear on, you know, your own personal website and blog and it seems like in treatment. But I want to, I guess, emphasize the point that are these weight loss drugs a panacea, a cure all, or what other factors should physicians and patients be considering?

Robert Kushner, MD 00:03:38 Well, certainly not a panacea.

Robert Kushner, MD 00:03:41 we have used the word game changer because of how more effective they are than previous medications. And I think to set the stage to your question, Richard, we have finally found an effective target for treating obesity after decades. And it's called the gut brain axis. So by targeting these naturally occurring hormones in our intestinal tract and pancreas, such as GLP one, GIP, amylin, glucagon, these are these are hormones that we learn about in medical school and during our training. We've we've found that if we could synthesize these hormones and give them back to people, they have a profound effect on appetite regulation and the effect on the heart, the pancreas, liver and so forth. Previous targets to obesity have always focused on on the central nervous system, like affecting appetite centers and hypothalamus and so on. And they had side effects that were modestly effective. But these gut hormones or nutrients stimulated, hormones that we now synthesize, give back to people are just woefully, woefully effective. So they're not a cure to obesity.

Robert Kushner, MD 00:04:50 They're not a panacea, but they are by by far the most effective medications that we have ever had. And Richard, there are more to come. This is just the beginning of really understanding how to use these medications, how to combine them, how to administer them. And I suspect, even more effective medication, not only for weight loss, but also regarding improved health.

Richard Payerchin 00:05:14 Doctor, there have been both formal studies as well as perhaps less formal media reports about potential side effects. And, you know, perhaps that those might be a little bit scary to some patients. apart from side effects or maybe just what are the most common questions that patients bring when they get into the exam room and they're talking to yourself and other physicians?

Robert Kushner, MD 00:05:39 Well, you know, I think because of this social media and the role of influencers and the hype around these medications, the story about them almost every week, if not more than once a week, Actually, the most common question patients have when they make an appointment is doctor or nurse practitioner, whoever the primary care provider is.

Robert Kushner, MD 00:06:01 Am I a candidate for these medications because they have a family member? They have a friend. They've read a blog by someone of how effective they've been in changing their life and causing weight loss. That's number one question. Am I a candidate? Once you then address that, then you get into more details. What can you expect from how much weight loss? How to manage the side effects? Is it covered by your insurance? You know, all these these questions that are necessary to follow up on. But am I a candidate is by far the most common question.

Richard Payerchin 00:06:34 And what are some of the characteristics? What makes a good candidate for these drugs or what might be you know, what patients, what patients are not good candidates?

Robert Kushner, MD 00:06:45 Yeah, that's a good question. So once they say my candidate, Of course. Then you have to go through. Are you a candidate? But what we tell them is, yes, you possibly are a candidate. And the reason I would say that is that the package insert the FDA approval for most of these medications is based on body mass index or BMI.

Robert Kushner, MD 00:07:05 So that's kind of the, the, the, the, the bottom line criteria. And that is if someone has a body mass index which is high, which is weight over height squared, it's how you can calculate it easily on the internet. If it's 30 or more that is associated with obesity and you are a candidate for that medication, or if your BMI is 27 or more with a complication like diabetes, hypertension, high triglycerides, sleep apnea, those types of things, you are also a candidate. So that is really a low bar to be a potential candidate for these medications. If you think about a typical typical individual United States 40, over 40% have obesity just just just statistically like that. But that only begins the conversation. Then we talk about do you have a contraindication such as such as a reason that we would not want to use this medication like a history of pancreatitis or, or allergy to medication or things like that? how much weight are you likely to lose? What other medical problems do you have that are likely to also be beneficial? do you, do you do you rather have an oral medication or an injectable medication? What are your likes or dislikes? And really, I would say unfortunately it all in this country it comes down to can you afford it? Do you have insurance coverage for it? Do you have access for it? That is really unfortunate.

Robert Kushner, MD 00:08:34 As a health care provider, that's the last thing I want to talk about. But unfortunately it's really the bottom line. Can you get it? Can you afford it and is it covered?

Richard Payerchin 00:08:46 Our magazine, of course, is medical economics, and I want to get into the cost factors, momentarily here. But I had seen online that you were involved with a seminal study working with semaglutide, and I didn't know, what are the actual medications that you yourself have prescribed to patients?

Robert Kushner, MD 00:09:03 Well, I've been in practice for over 40 years, so if you could, if you could think of the medication I've prescribed it, and I, and I still prescribe many of the medications, if not all, that are available in the US market. However, because the newer medications, these these nutrients, stimulated hormone based therapeutics, which are semaglutide intercepted. Liraglutide also is in that category. But it's less effective because it's every day and it's the overall weight loss is less. We we typically use we try to use those medications more often because they're more highly effective.

Robert Kushner, MD 00:09:41 But then we get into the coverage, Point of view. If they are not covered, then we'll often make the decision based on cost and that is what can you afford, either out of pocket or getting it through a pharmacy that has more a lower cost or what's covered by your insurance. So the conversation is longer than I would like being a clinician where I prescribe the best medication for you and it's covered, but unfortunately that's not the situation. So we'll start with the most effective if there's no contraindications. But if that's not available, then we'll move to other medications. They'll be less effective but at least available to you. And it'll be more on a cost availability basis.

Richard Payerchin 00:10:24 Doctor, if I may, let me kind of work on a train of thought here, because that was sort of an interesting segue. I really kind of wasn't expecting, because one of the sample questions that I had was, do you consider these medicines as a next step in a treatment regimen? And it sounds like, based on the economics of it.

Richard Payerchin 00:10:42 It might be a first step, but but not an available step. And and I guess can you talk maybe a little bit about that. You know, if a patient does have trouble affording it how do you counsel them then.

Robert Kushner, MD 00:10:55 Well let me, let me, let me set the stage to answer your question. As we think of obesity as a chronic relapsing disease like other chronic relapsing disease. And the best comparator I can make is diabetes. So if I had someone come in with diabetes and their blood sugar is woefully out of control and they're already having different complications or signs or symptoms of diabetes, that is that is severe, I wouldn't say let's start with metformin and see how you do. And we'll build up slowly to insulin. We wouldn't do that. We would treat the severity of the disease as soon as we see individuals. I want you on a on a diet to your regimen that's going to improve. You improve your diabetes. But we're going to start insulin today. We're going to start a highly effective medication because that's going to get us to where we need to be.

Robert Kushner, MD 00:11:43 It's called treat to target. In obesity, we really should think of it the same way. If I have someone with, for example, severe obesity who already has sleep apnea, has fatty liver disease. I'm going to think about the most effective treatment available. I'm not going to start with, let's say orlistat, which blocks dietary fat from being absorbed. It's not terribly effective. We're going to go to the most effective medication. But again where the where the conflict comes in is that the highly effective medication is not always the one that is covered by the individual's health plan or the Medicare, Medicaid and so forth. So we always have to, in our mind, negotiate what's the most effective medication for that patient given what is available and affordable.

Keith Reynolds 00:12:33 Oh, you say you're a practice leader or administrator. We've got just the thing. Our sister site, Physicians Practice. Your one stop shop for all the expert tips and tricks that will get your practice really humming again. That's physicians practice.

Richard Payerchin 00:12:52 You are going to have a new book coming out titled Patient Centered Weight Management.

Richard Payerchin 00:12:56 The six factor Professional Program and toolkit. What else should especially primary care physicians and other clinicians know when they're addressing these drugs, with these with their patients?

Robert Kushner, MD 00:13:10 Richard, you've done your research. I'm impressed. the books that I've written have primarily focused on the behavioral and lifestyle support of individuals, and that is that is what I'm trained in. And that's what I always want to emphasize when I talk to clinicians. Yes. Pharmacotherapy has a very important role in treating individuals living with obesity because they're highly effective. And they treat Not just weight loss, but other complications. However, all medications sit on a foundation of lifestyle and that is how do you live your life? Are your diet you choose and the patterns of the diet, how you move your body around, your physical activity and your exercise. How you cope with stress. Whether you get adequate sleep, whether you're socially isolated, isolated in your community, or you're engaged in your community. All of these variables are so important for overall health. And I'll give you a good example.

Robert Kushner, MD 00:14:09 If I give you a medication that reduces your appetite. And that's how these medications work and you feel less hungry or full sooner, that doesn't necessarily teach you how to eat healthily, how to choose a pattern of diet with fruits and vegetables and whole grains and and reduced and ultra processed foods. You don't know that it doesn't come with a package insert or or a guide. So if I can help someone manage their appetite, I then come in and give them a foundation of how to eat healthier. Given the reduction in appetite and in addition to that, we're going to talk about how to move your body around to more, how to deal with stress, how to sleep more healthily. So that's really what my books are about. And the book you mentioned is A Practitioner's Guide to another book I wrote, which is Six Factors of fit, which is all on a phenotypic presentation of individuals when they see you in the office, and how you can quickly identify what those targets are. When it comes to behavioural change.

Richard Payerchin 00:15:10 Doctor, I wanted to throw this out there because it it is it is an unfortunate reality that, you know, a lot of patients may be bombarded with medical misinformation. And frankly, there are people out there just trying to make a buck. With the proliferation of fake semaglutide and other counterfeit forms of these drugs. How do what's the best way for physicians to talk to patients about avoiding scams and, frankly, potentially putting dangerous substances into their body?

Robert Kushner, MD 00:15:40 Well, certainly there's no role for counterfeit medications. Those are illegal, and you should stay away from them entirely. However, the hottest issue is compounded pharmacies and compounded medications, which are really proliferating because of a time of shortage of the trade name medications. And I just want to emphasize that compounded pharmacies are approved and can be used in times of shortage. The FDA actually supports that. And that's why compounding pharmacies and compounding medications are available, because the FDA has deemed the two trade medications for semaglutide appetite as shortage. So if you were going to be taking a compounded medication or prescribing one, if you're a prescriber, you need to know where that active ingredient is coming from.

Robert Kushner, MD 00:16:30 You have to understand what pharmacy is actually compounding it. Do they have good manufacturing practice? Do they have quality assurance? do dosing instructions come with it? have there been any side effects or safety concerns coming out of that pharmacy? And that all makes sense. But but in reality, what patient and what provider has that kind of time and skill in literacy to actually do all that research. So it becomes very, very conflicting. I am very concerned about using compounding pharmacies because the number one issue is safety. And when I am asking someone to draw up in a needle and syringe, a, a pharmaceutical product and inject them injected in them, which is what's done. I'm very concerned about safety. If I don't know what that brand name is. So it is approved. But know what you are actually using.

Richard Payerchin 00:17:26 Doctor, I want to go back a few years. And one of the things that is remarkable to me is the speed with which things are developing. But in that, I think it was 2021 study that you had worked with.

Richard Payerchin 00:17:39 I remember seeing or kind of from the one podcast you had discussed of a, I believe, a seven, a 7% dropout rate. I want to I want to go with, based on the semaglutide study, a 7% dropout rate, which, you know, begs the question, it's a 93% acceptance rate. And where I'm going with that is it the vast majority of patients were able to tolerate any upset stomach or nausea, any of those side effects that come with the GLP one RA drugs? And where I'm going with this is based on that. Again, vast majority of patients, you know, really being able to tolerate those side effects. Was that a surprise to you? I mean did that did you expect Better or worse? I'm just curious about that.

Robert Kushner, MD 00:18:30 Well, when we when we look at data from phase three trials, that doesn't represent real world experience. So we need to make that connection when it comes to trials. Generally individuals have to reach a particular dose. And if they can't reach a dose, they have to drop out because we we often don't have them continue because we're learning the safety and efficacy and tolerability of a particular dose.

Robert Kushner, MD 00:18:52 That's going to get FDA labeling. So dropout rates may may differ. But we learn so much by doing that phase three trial because we learned how often, individuals develop gastrointestinal side effects. Those are the most common ones nausea, vomiting. It could be constipation, diarrhea, heartburn. Those are really the common side effects. So we learned how often do they occur? How severe are they mild or moderate or severe. And probably the most important thing we learned is how to mitigate those side effects in individual in a trial. So we've taken that experience of how to change the diet in council individuals and bring that into the clinic, which is a real world experience and help people stay on the medication because of what we have learned now, in real world experience, dropout rate is likely to be higher because clinicians don't have the time and the skill and experience to hold a patient's hand week by week as we dose escalate. unless you're relegated to perhaps someone else in the office is going to be doing that with you.

Robert Kushner, MD 00:20:00 but patients often may have a side effect and say, I don't want to use that anymore. Never contact our provider again. So we have to we have to use a different practice system often in the clinic versus in the trial. but we're always going to have people drop out, in my experience. And what I've been reading, the reasons for not continuing a medication today is, is the side effects that are, that are not being tolerated. And again, it could be because the clinician is not watching or helping a patient as closely as we did in the trials, or unfortunately, they can't get the drug because of the shortage. So they're dropping out because their pharmacy is no longer able to stock the medication for them.

Sydney Jennings 00:20:44 Say, Keith, this is all well and good, but what if someone is looking for more clinical information?

Keith Reynolds 00:20:49 Well, then they want to check out our sister site, Patient Care Online. Com the leading clinical resource for primary care physicians. Again that's patient care online.com.

Richard Payerchin 00:21:04 We're a few years out from that 2021 study.

Richard Payerchin 00:21:10 What about five years from now? Ten years from now. What what what are your. Do you have any concerns about long term main effects or side effects?

Robert Kushner, MD 00:21:18 Well, I can tell you what we know right now from a data point of point of view. And that is we just completed the select trial, which was a global trial looking at the effect of using semaglutide 2.4mg administered weekly in individuals with preexisting cardiovascular disease, had a prior stroke, prior heart attack, or peripheral arterial disease. And the question is, is if we use semaglutide, can we reduce the occurrence of a secondary event like a second heart attack or a second stroke or cardiovascular death? And the results of the study were very positive. The very first time ever that we saw that a drug that's approved for weight loss can significantly reduce Mace, which is major adverse cardiac events in this population. So that's that's that's a separate story. It actually led to a difference in the labeling for the drug by the FDA. So instead of a BMI threshold which we talked about earlier Richard, now it just says someone with obesity with existing cardiovascular disease.

Robert Kushner, MD 00:22:18 So they threw out BMI which was wonderful. But the question you ask is safety concerns. So select is the longest trial we have for individuals around these medications out to four years. So that's the longest that we have with this high dose of semaglutide. And we did not see any untoward side effects that we did not anticipate. Mostly GI side effects. But the other thing that I rely on regarding this is that these drugs, particular semaglutide, has been available since 2017 under a different trade name for diabetes and used globally in hundreds of thousands of individuals. And we have not seen a serious adverse event or safety concern with a lower dose of semaglutide used now for, you know, 7 or 8 years, and since 2001, of course, same drug but a higher dose. So as you know, we have post surveillance mechanisms that the FDA requires or individuals upload or report safety concerns, and if enough safety concerns are reported, then they do a deeper dive into looking at causality rather than just correlation. And as of now, we have not seen that.

Richard Payerchin 00:23:32 And doctor, you touched on this, I think, at the start of our conversation here. can you can you look in the crystal ball, so to speak, and talk a little bit about, you know, your predictions in the future here of what's going to happen, number one, medically and then number two financially, if there will be increased coverage, you know, based on of these medications based on their health effects.

Robert Kushner, MD 00:23:54 Well, as I as I said before, we have we have changed the target for treatment of obesity to what we call the gut brain axis. It is excuse me. It is a significant paradigm shift in the treatment of obesity, discovery of these hormones as it relates to appetite regulation and overall health of multiple organs. So the availability of GLP one receptor agonist. And of course we have another drug tres apatite which is a dual agonist is GIP, GLP one receptor agonist. Both those are the two on the market now. But there are other hormones that are now being investigated, typically in combination with GLP one.

Robert Kushner, MD 00:24:36 And that's glucagon and amylin. And these are even more powerful medications so far in these phase two, phase three trials with greater effect on different organ systems. In addition, there are ongoing trials to make what's called small molecules. So it's a GLP one receptor agonist. But instead of giving it as a peptide which must be injected, they're doing it as a small molecule that could be taken orally. So we can anticipate in a very short period of time, there will be highly effective medications that that kind of mimic what we give by injection. But now being given orally as a daily tablet, which really brings the costs down. And I think the generalizability of these medications. The cost clearly has to come down. the the Medicare now approves the semaglutide 2.4 because of the select trial. It approves it for those individuals with preexisting cardiovascular disease and obesity. But that doesn't mean that they're paying for it fully. They just approved it. So, the door is starting to crack open for the generalizability of these drugs.

Robert Kushner, MD 00:25:42 And I think as more of these drugs are showing health benefits, particularly regarding cardiovascular disease, they are going to be approved because we don't want to keep them back from the population of highly effective medications. So you know, where where the door is going to really crack wide open regarding bringing the costs down and making them available to the general public. I don't know when that's going to happen, but it has to happen. Renegotiation of prices. We know government is involved now in capping the cost of medications. So those may come up at some point regarding capping it. medications are going to go generic. So there'll be there'll be cost equivalence of medications as they go off patent. So probably a series of events. But the costs clearly have to come down.

Richard Payerchin 00:26:29 Doctor I'm keeping an eye on the clock here. And frankly, I could there's about 40 more questions I could throw out. depending on your time. But I'm going to let you get back to your your regular duties here. Although I did.

Robert Kushner, MD 00:26:39 Want.

Robert Kushner, MD 00:26:39 Okay.

Richard Payerchin 00:26:40 Our main audience is primary care physicians. What would you like to say to them, or what would you like them to know about this topic?

Robert Kushner, MD 00:26:46 Yeah.

Robert Kushner, MD 00:26:48 we are truly at a threshold of significant change in our ability to manage patients living with obesity with all the complications of comorbidities they have. Every primary care clinician sees patients who are struggling with their weight and developing complications and comorbidities. This is not a unicorn. This is something that we see every single day. And what I would say is that the the effectiveness and availability of these medications will probably remain on the shelf if you don't become familiar and competent with how to use these medications combined with lifestyle management. Now that could be a heavy lift for many clinicians who are not trained in obesity during during medical school or during their professional school. But you have to become familiar and competent and be proactive in managing your patients. Otherwise, your patient will not get the benefit from it, and these medications will not be used as as intended. And that is across the population for those who would would be benefited from their use.

Richard Payerchin 00:27:59 You know, doctor, thank you for taking the time here. I really enjoyed our conversation and I hate to feel like I'm cutting you off, but like I said, I'll let you get back to your regular duties and especially because you had to rearrange your schedule. So thank you so much.

Robert Kushner, MD 00:28:09 Well, thank you, Richard I appreciate it.

Keith Reynolds 00:28:21 Again, that was medical economics senior editor Richard Paragon and Doctor Robert Kushner, professor of medicine and medical education at Northwestern University. My name is Keith Reynolds. And on behalf of the whole medical economics and physicians practice teams, I'd like to thank you for listening and ask that you please subscribe to the show on Apple Podcasts and Spotify. Also, if you'd like the best stories Medical Economics and Physicians Practice Publish delivered straight to your email every single day of the week. Subscribe to our newsletter at Medical Economics and Physicians Practice medical economics, Physicians practice and patient care online are all members of the life sciences family. Thank you.