Speaker 1:

Welcome to AACE Podcasts. Thanks for tuning in as we elevate clinical endocrinology by taking deep dives into trends and topics that can help us improve our patient care and global health. Find the latest episodes on aace.com/podcasts. And now let's meet the endocrine experts who will be talking with us today.

Dr. Nadeem:

Welcome to another episode of the AACE Podcast. I'm Dr. Sarah Nadeem, Endocrinologist in the faculty at Baylor College of Medicine in Houston, Texas. I'm also Staff Physician at the Michael E DeBakey VA Medical Center. My area of expertise is diabetes, diabetes technology, and obesity and metabolic disease. I have worked and practiced in Chicago, Houston, and Pakistan. Today, we will be discussing sleep apnea and metabolic disease, the evaluation and therapeutic management. So before we begin, I would like to thank our sponsors for this AACE Podcast, Lilly for supporting this important conversation. Joining me today are Dr. Abbasi-Feinberg and Dr. Madahar. Thank you both for being here. Dr. Abbasi-Feinberg, let's start with you. Could you please introduce yourself and share a little bit about your background and area of expertise?

Dr. Abbasi-Feinberg:

Hi, my name is Fariha Abbasi-Feinberg. I am a Board Certified Sleep Medicine Specialist. My background is in neurology, so we can get into sleep medicine a couple of different ways. I am Medical Director of Sleep Medicine at Millennium Physician Group in Fort Myers, Florida. And I also serve as the President-elect for the American Academy of Sleep Medicine. I've been practicing clinical sleep medicine for over 20 years, taking care of patients day in and day out. And I love talking about sleep and how it affects your health and your wellbeing. So thank you so much for having me here.

Dr. Nadeem:

Absolutely, thank you for joining us. And Dr. Madahar, could you please also tell us a little bit about your clinical background, introduce yourself, and what your clinical focus is?

Dr. Madahar:

Hi, thank you. First of all, thank you for having me. My name is Inderpreet Madahar. I'm a Board-certified Endocrinologist. Currently, I'm working for Corewell Health in Saint Joseph, Michigan. My area of expertise is mainly diabetes, lipids, and obesity. Very much interested in treating metabolic syndrome.

Dr. Nadeem:

Okay, let's dive into our discussion. So the first question I'll start with Dr. Abbasi. So as a sleep specialist physician, if you can describe the pathophysiology of obstructive sleep apnea and who is at highest risk of developing this disorder.

Dr. Abbasi-Feinberg:

Yeah, absolutely, it's such an important question. So an apnea is defined as a cessation of breath, right. For our audience here today, we're going to be focusing on obstructive sleep apnea. So as the name implies, there's some type of an obstruction, a closure of the airway. Now that can be from something anatomical or it could be from a physiologic factor as well. Now when we look at apneas, we have criteria for it. So the event has to last for at least 10 seconds. There has to be an associated drop in oxygen saturation. And when we look at the sleep studies, we add up all of these events and then divide either by the number of hours of sleep recorded or the number of hours of according depending on what type of sleep study we're doing. And we come up with an Event Index. And that event index then helps us classify if somebody has mild, moderate, or severe obstructive sleep apnea. You asked about who's at risk? Well, anybody that has a smaller airway or a crowded airway is at risk, and that can be from a lot of different things. So sometimes, you know, enlarged tonsils can do it, macroglossia can do it, retrognathia or micrognathia can do it. Obesity is often associated with sleep apnea as well. Definitely a higher risk for men, but I don't wanna leave us women out because women do have risk for sleep apnea. And especially as we get to the perimenopausal and menopausal ages, that has to be something that's really evaluated, you know, consistently.

Dr. Nadeem:

Thank you, that's very helpful. So do you feel like sometimes, as you mentioned in women, it's overlooked and not screened as often?

Dr. Abbasi-Feinberg:

Yeah, I think that is a huge problem that we see in the sleep world all the time. You know, I think women are often discounted when they come in because they present a little bit differently. So just like in heart disease, you know, women may not have that clutching chest pain like men do. Women with sleep apnea usually present a little bit differently. So they can have more sleep disturbance. They can come in with insomnia. They say more, "I'm fatigued," whereas, you know, men tend to doze off a little bit more. And of course, these are big generalities. But I think when a woman comes in, especially if she has other risk factors and if she's of that perimenopausal/menopausal age, it's something that we have to look at.

Dr. Nadeem:

Right, that's very helpful. So Dr. Madahar, can you help talk a little bit about how metabolic disorders and sleep apnea are related, and what's the bidirectional role or relationship between the two?

Dr. Madahar:

Oh yes, obstructive sleep apnea and several metabolic disorders, like insulin resistance, obesity, diabetes, they share a bidirectional relationship, meaning one enhances the development of the other. So how I usually explain it to my patients is when your body doesn't get enough rest when you're sleeping because of lower levels of oxygen, brain doesn't feel rested enough. It kind of feels like as it's going through a stressful phase and starts signaling for a higher caloric intake. So that results in increased cravings. And it makes it harder for them to lose weight and results in uncontrolled diabetes. And in turn, obesity, it further worsens obstructive sleep apnea that further creates a vicious cycle. So this is basically a layman's kind of explanation. I would explain more scientifically would be through two main mechanisms by which OSA, the obstructive sleep apnea, could worsen diabetes and obesity, that would be intermittent hypoxia and sleep fragmentation. So these two mechanisms, they can provoke beta-cell dysfunction, pancreatic beta-cell dysfunction, and insulin resistance. The alternative hypothesis is they are possibly creating a stressful alternative hypothesis is activation of the HPA axis, the hypothalamic-pituitary-adrenal axis as a stress response that results in increased glucose production in gluconeogenesis and reduced uptake of glucose in the adipose tissue. That further results in hyperglycemia. Also patients with obstructive sleep apnea, they're noted to have higher levels of inflammation because of elevated levels of cytokines in comparison to someone who does not have sleep apnea that can further worsen the insulin resistance. And recurrent arousals, they may result in circadian misalignment that can cause metabolic conditions like lower melatonin levels that further increases the risk of type 2 diabetes. So now we have seen that OSA is highly prevalent in type 2 diabetes, but it has also been reported highly in type 1 diabetic patients. So that further raises the possibility that this disorder could possibly be just not associated with just adiposity, but also hyperglycemia. So chronic exposure to hyperglycemia that could attenuate the carotid body discharge rate that could result in degeneration of the carotid body parenchyma resulting in dampening of the hypoxic reactivity and hence high risk of obstructive sleep apnea. So those are few mechanisms by which OSA and diabetes they're affecting each other. So sleep fragmentation that results in lower reduction of slow-wave sleep. That is basically the deep sleep that is important for glucose regulation that can increase the cortisol and growth hormone, rise in cortisol and growth hormone levels at inappropriate time resulting in higher glucose levels and a higher dwelling that is basically the hunger hormone and lower leptin that promotes weight gain. So when you are lowering leptin or in obesity when leptin resistance arises, so leptin is basically responsible for stimulating the breathing control in the brainstem in obesity and insulin resistance. Leptin resistance can also impair the ventilatory drive that makes the apneas more likely. So this is basically how obesity and OSA are interacting with each other. So most common how we explain it to the patients is basically when your kind of neck mass increases that under the neck mass, the airway could collapse and that could make your obstructive sleep apnea even more worse. So that is basically the bidirectional relationship.

Dr. Nadeem:

That's very helpful, and as you mentioned, you know, there are multiple pathways that are postulated and I know we had talked about whether we're gonna focus just on OSA or central sleep apnea, but if Fariha you could talk a little bit as Inderpreet mentioned that you know, the central aspect is also there. So is it always very pure just OSA or in metabolic syndrome or people with obesity and diabetes? Could it be a combination of the two?

Dr. Abbasi-Feinberg:

Yeah, I mean the obstructive sleep apnea is just so much more common, right? There's a lot of different reasons that people can have central sleep apnea and sometimes we see it when there's like some arousals going on. Believe it or not, there's something that we call post-arousals central events and they're, you know, we don't really classify them as being pathologic so they can be there but they may not be a problem but they occur because the sleep is very disrupted and the sleep is probably disrupted from the obstructive events in that particular situation. Now there are times that somebody has neurologic disease associated with it or if they're on certain medications such as opioid medications, those obviously increase the risk of central events as well. And then if you have congestive heart failure, that's another big risk factor. So I think in the usual population that most of your audience is going to see, I think it's really the obstructive events that are the bigger factor.

Dr. Nadeem:

As you were mentioning, the wider neck. So coming back to you know, like type 1 population or in women, would that criteria still hold or because that may not be the same risk factor as we say, you know, a wider neck diameter would prompt you to assess for obstructive sleep apnea.

Dr. Madahar:

So it's more about the neck mass, not about the wider neck, I would particularly say. So it's basically obesity and women as we know that they are kind of more prone

Dr. Nadeem:

And I think that brings us to, you know, then who should we be screening for sleep apnea as endocrinologists, as primary care physicians and what screening tools would be utilizing? And I'll begin with Inderpreet and then Fariha you can chime in as well.

Dr. Madahar:

Sure, from endocrinology standpoint, I would like to screen anyone who's BMI is more than 30, you know, especially with central adiposity, any male more than 17 inches neck circumference or any female more than 16 inches neck circumference, rapid unexplained weight gain if you're seeing in some patients, type 2 diabetes, pre-diabetes, metabolic syndrome resistant or difficult to control hypertension, different endocrinology cases like acromegaly, hypothyroidism, which prone patients to high risk of obstructive sleep apnea, PCOS, Cushing's syndrome, Cushing's diseases or pheochromocytoma. All these patients would qualify for screening of obstructive sleep apnea. Also, I think most of the patients I see in my clinic, they're usually complaining of unexplained fatigue. That's where I kind of suspect mostly obstructive sleep apnea and that's when I refer them to our Sleep Medicine clinic.

Dr. Nadeem:

And Fariha would you add to that list?

Dr. Abbasi-Feinberg:

Yeah, I mean that's an excellent, very thorough list. So now, I appreciate that. I think, you know, there's a couple of different screening tools that are out there and the one that's used most commonly is called a STOP-BANG. It's basically eight questions that are either yes or no and then you add up your points and then you can decide if somebody's at low risk, intermediate risk, or high risk of obstructive sleep apnea. And the questions are very, very simple. So S stands for do you snore, T's are you tired, O is there observed apneas, P is do you have pressure, high blood pressure issues, B is body mass index, A is age over the age of certain time, what's your neck circumference? And as Inderpreet said, you know, 17 inches for men, 16 inches for women. And then the last one is, are you a male, right? So certain things there you cannot change. And so you have those risk factors. So if you score five to eight yeses, your risk of having sleep apnea is pretty high. Now asking eight questions in every visit may be too much. So if you can embed something like that in the EMR that offers helps. But you know, as non-sleep specialists, I would love it if primary care physicians and endocrinologists would just ask one simple question. And that simple question is how do you sleep? Right, because so often it is not something that's focused on and if the patient says, you know, I sleep great, then you can whiz right by it and then go to other important issues that they're there for. But if the patient says, you know, I don't sleep well, then you can ask the next follow-up question, do you snore or are you tired? And then go down that route and figure out if that person needs a referral or a sleep study and how you wanna approach that.

Dr. Nadeem:

For sure, I think we need to talk about it more often and consider it especially with, as Inderpreet also said, we see a lot of patients who come in with non-specific fatigue symptoms and just getting a little bit of the sleep history will sometimes often say, yes, you know, I can't sleep or I wake up or my, you know, their partner has pointed out to them snoring a lot or stopping, you know, breathing in the middle of the night. I think that kind of, once you start asking those questions, we get the whole picture. Looking at this information, looking at who we should screen, I guess the question I would have is, is it different between ethnicities? Does the risk factors, is the prevalence different in terms of even the BMI and coming from South Asian background myself, the obesity and overweight criteria for BMI, which is still not, I mean BMI is not the best criteria, but that's what we have is different and at lower BMI there's increased cardiovascular risk. So does that also hold true for OSA risk?

Dr. Abbasi-Feinberg:

Prevalence estimates are that's it's about 15% of the population has sleep apnea and that's sort of being conservative I think, you know, if you look at the U.S population, we're talking about 50 million people that may have sleep apnea and we have data that 80% or more may be undiagnosed. When we're looking at a worldwide population, numbers that I've seen are as high as a billion people may have obstructive sleep apnea, right? So it's a very common disorder. You're absolutely right that in different populations, you have to look at it differently. So I'm also southeast Asian and you know, when we look at our airwaves and our facial structure, there are some anatomical differences. So there is a higher risk in folks from Asia, Southeast Asia versus some European countries as well. So you do have to look at that and I think, you know, we all struggle with is the BMI the appropriate measure of risk and I think talking about central adiposity helps and also just looking at where the adiposity is, right? So I mean if somebody's got the extra weight in the hips, maybe we don't worry quite as much as if they have it all around their face and you know, so I think there's those ways to look at it as well.

Dr. Nadeem:

Great, thank you. Inderpreet any input, what are your answer?

Dr. Madahar:

I think I see more obstructive apnea in African-American population. I feel it could be because of you know, lack of proper healthcare availability to African-American population that is, and mainly I see higher A1Cs, so that's what I'm kind of increasingly seeing. The area where I'm practicing, I don't see a whole lot of South Asian population but most of them that I see they have sleep apnea. So it's kind of area of my interest too.

Dr. Nadeem:

And just picking up on your answer there, in terms of A1C, is there a correlation between uncontrolled diabetes and increased incidence of OSA in that patient?

Dr. Madahar:

Yes, so higher uncontrolled diabetes is seen in mainly patients with moderate to severe OSA, not as much with mild OSA. So yes, there is a correlation.

Dr. Nadeem:

Yes, that's helpful. So it's kind of both of them feed off each other and kind of make it worse.

Dr. Madahar:

Yes. Basically a visious cycle.

Dr. Nadeem:

Once we make a diagnosis, I believe we do the screening test and as an endocrinologist my next step is usually if high suspicion or a high score then I would refer to a sleep specialist for a sleep study. Fariha, is that the right approach to take?

Dr. Abbasi-Feinberg:

Yeah, I know it's difficult to get into a sleep specialist these days, right? It's almost as difficult as getting into an endocrinologist because you guys are very busy people and so, you know, I think we're looking at different practice models to make this easy, make this accessible for our colleagues but also our patients, doing a sleep study is the right next step. There are different types of sleep studies. There's sleep studies where you come into the sleep lab and you spend the night and most of the time these days we do home sleep apnea tests and they're getting better and better with newer technologies that make it simpler. So we're trying to figure out how we increase access of care for everybody and make life easier. Yes, that would be the next step. And then once we have the diagnosis, you know we have a couple of different options available and we can go from there.

Dr. Nadeem:

And so what do you recommend as the first-line management of therapy once you made that diagnosis of OSA?

Dr. Abbasi-Feinberg:

You know, I really look at what's going on with the whole patient. You know, it's not that one size fits all. Everybody thinks that oh, as soon as you're diagnosed somebody is going to slap a CPAP on you but that is not the case. You know, you have to evaluate and see okay, what's going on? For some people weight loss is the best choice and if they have mild apnea, maybe that could be the sole intervention but if you have more moderate or severe, you can do it in combination, right. There are times that I look at somebody's sleep study and I see that all of their events occur when they're flat on their back. So you can do positional therapy on their various devices, either electronic or physical devices that help somebody sleep on their side versus their back. So you can help with that. There is a device called the eXciteOSA, it's a neuromuscular electrical activation stimulation that you put on the back of your tongue and it massages and strengthens the muscles in the back of the tongue. There are, you know, mandibular advancement devices that we use and I'm a big fan of those for the right people. We have surgeries available, you know, in the past we used to do the UPPPs and the maxillomandibular advancement procedures. We don't do as many of those as we used to once because now we have hypoglossal nerve stimulation that's available and I consider that surgical and you know, up till last week we had one device that was FDA-approved and hot off the presses just last week, another one got FDA-approved. And then the other new thing is there's a couple of pharmacologic interventions that are going to be available. They're not available yet besides, you know, the weight loss option that we're gonna probably talk about. Now out of all of those, you're right, PAP therapy still tends to be our first option because it's effective, you know, people actually can tolerate it. CPAP has a bad wrap but I cannot tell you the number of people who think that CPAP device is their most valued treasure and in case of emergency evacuation, that's what they're going to grab to leave the house, right. And so there's lots of people that love CPAP. When we look at data that's based on large cloud-based data sets, at least 70% of our patients do really well with CPAP therapy. And you know, if we compare that to how many people take their anti-hypertensives, that's only 50%. So I think 70% is actually pretty darn good. And then if you throw in some modern technology with active patient engagement and some AI boosts the rate of people using it, compliance goes up to about 80%. So I think, you know, PAP therapy is still our gold standard, but you have to look at the whole situation.

Dr. Nadeem:

Yes, so I think, you know, there's also this historical perspective about this bigger CPAP machine or bigger mass and I think people who may have abandoned their machines years ago, they probably can be nudged to go back to the sleep physician, which I end up having to do for a bunch of my patients because from my understanding now the devices, the mask, they've changed, they're more comfortable, is that correct?

Dr. Abbasi-Feinberg:

That's absolutely correct. You know, I'm a big cheerleader for patients and so often people will come in and when I go through my usual spiel about the options, you know when I mention CPAP, they roll their eyes at me. And I always just laugh and I say don't roll your eyes, let's wait and see, and you know, there's a process of desensitization that you can work through with people. You know, I think you have to engage the person ahead of time and their bed partner. If their bed partner doesn't buy in, then you're out of luck, right? Because everything that you do is going to bother them. And so it's a team effort. So I always love having their bed partner with them when they're there for their visit so that they can hear what's going on and we work through the process and I'm there to help them work through the process because there's lots of little tweaks and adjustments that I can make to help them with things. And I think just knowing that someone's gonna be there to hold their hand is something that's very, very helpful to my patients.

Dr. Nadeem:

Yeah, that would be valuable 'cause like you said, you know, a lot of times when I mention that, you know and they're like oh, I know how they treated and I'm like no, just go and discuss the options at least so I think for sure. Inderpreet can you talk a little bit about, you know, if you also see initial hesitancy amongst your patients about treatment and then if you can talk a little bit about adjunct treatments that are available.

Dr. Madahar:

So like Dr. Abbasi said initial hesitancy with CPAP therapy. When I start screening my patients for obstructive sleep apnea, they always have this question, if you're gonna put that machine on, I'm not gonna go to that sleep medicine doctor again like because all they have to offer is the CPAP, but then again we are kind of talking to them about how the technology is improving just like diabetes technology, how about insulin pumps? And this is how I kind of get them to discuss more of sleep apnea with me that more as we kind of advance more technologies coming our way. So that will be more helpful, so that is one. Second is I talk to them mainly about weight loss treatments because with the latest SURMOUNT-OSA trial that came out that led to FDA approval of tirzepatide or the brand name Zepbound for obstructive sleep apnea treatment. So that kind of opened many avenues for treatment of patients with obstructive sleep apnea. So now I proactively screen obese patients for moderate to severe OSA even when they're consulting primarily for type 2 diabetes, metabolic syndrome or for obesity. And we have a really good sleep medicine clinic and the collaboration with them that has helped me to ensure that sleep studies are done timely for these candidates. So for patients who are kind of meeting the criteria that obesity plus moderate to severe obstructive sleep apnea. So that's when we are kind of helping them to get Zepbound prioritized through insurance in a timely manner. So initially it was only for obesity, so now we are kind of making sure that obstructive sleep apnea is properly documented in their chart so that you know, insurance also they know that this is what we are using it for not just for weight loss. So yeah that is the alternative treatment available from endocrinology standpoint.

Dr. Nadeem:

Thank you, thank you for sharing the FDA label expansion for tirzepatide being from moderate to severe OSA as well. Have you felt that has changed your practice when you initially see a patient? Is that something that the patients are asking for or are they already on a CPAP and then that's something added on?

Dr. Abbasi-Feinberg:

Yeah, I mean it's been exciting because honestly the number of people that are willing to get evaluated has gone up, right? And so it has raised awareness again about sleep disorders and sleep apnea and you know, people come in with a slightly different viewpoint as to okay, you know, there's hope. And so I think just have that feeling of hope is great. I have a lot of my patients that are on CPAP that are doing well that ask about tirzepatide and if they are the appropriate candidates, I have no problem with prescribing that for them. You know, I've seen great success over the last year or two. I mean there were people that were taking medications even prior to it becoming FDA-approved, right. They were taking it for other reasons or they were taking it off-label and they have done extremely well. And so it's been an exciting time to be in sleep medicine because we are seeing something that's really moving the needle for our patients. So I see a lot of patients that are on CPAP doing it. I do have some people that come in and that's what they want and if they don't meet the criteria, for instance if they have mild sleep apnea, they're not thrilled about it but I talk 'em into other options at that point. And then, you know, some folks just want tirzepatide. They don't understand that we should probably also be treating their sleep apnea along the way and then eventually we can reevaluate them. So if somebody has, you know, hypoxia down to 61% and they're, you know, apnea-hypopnea index is 100, you know, I'm not gonna just give them tirzepatide, I'm going to convince them that we have to do more. But again, I think once people are in the office, you can talk to them appropriately and educate and you know they can take it from there.

Dr. Nadeem:

I'm very happy to hear that you're very comfortable prescribing tirzepatide. But I have seen, at least in my practice is that a lot of times, you know, we identify, you know they're diagnosed with OSA, start an CPAP, usually the prescribing falls to the endocrinologist. I don't know if that's your experience as well.

Dr. Madahar:

Yes, it has been.

Dr. Abbasi-Feinberg:

Yeah, I have to admit I didn't go willingly but I well, right when it first was FDA-approved, I thought okay, I'm gonna work with my primary care colleagues and my endocrinology colleagues, but everyone's busy, everyone has full schedules and trying to get these patients help in a timely manner fell back on me. And you know, I've talked to a lot of my sleep colleagues and there's some that are prescribing in are comfortable, there's some that are not. And I think it depends where you practice and what kind of support you have. I insist that my patients also talk to a nutritionist, dietician and I get them involved with that as well because I feel like I want them to have long-term success and you know, everybody wants that quick fix but you don't succeed long-term with just that quick fix. You're gonna have to make some changes and we still don't know long-term what we're going to do with these people in a year from now, two years from now if their sleep apnea is gone, you know, will insurance now stopped providing them their medication because now they don't have an indication anymore or will these people continue to be able to get the medication that they need? 'Cause obesity, as we all know it, is a long-term management issue, right. So there's still some unknowns and I'm maneuvering through and hopefully we'll figure it out with your guys' help.

Dr. Nadeem:

Thanks, yes, I agree with you. Like in terms of chronic disease, obesity is considered a chronic disease and I'll give the example of diabetes. So a lot of the GLP-1s, you know, sometimes people end up losing a lot of weight and they're diabetes is really well controlled. I have patients asking about, you know, so now it's gone like the diabetes is gone or the A1C is so much better but kind of reframing it that this is a chronic disease and this is a chronic medication. But I understand the concerns we all also have and have struggled with is that will insurance be covering it once you know the parameters all improve. So do you consider, Inderpreet, you can chime in on this one, when you would start tirzepatide for OSA and/or obesity, is this a discussion that you have with your patients about the long-term management and you know, that it's not short-term?

Dr. Madahar:

Yes, always. I always start with the lifestyle advisors first that you know, diet and exercise always have to come first and third avenue is the medication. So I tell them that you see if you are not gonna follow the diet and exercise pattern, the medication has to be you know, a long-term kind of mode of treatment but if you can lose weight but just diet and exercise, it's gonna kind of help you keep that weight off. Not promising that it's gonna be off in the next few months or the medication will be discontinued in the next few months. But I do talk to them about the SURMOUNT-OSA trial that when we are comparing just the use of tirzepatide as compared to just diet and exercise, the improvement in apnea-hypopnea index was much more as compared to just diet and exercise alone. So if they are kind of not losing enough weight despite the use of Zepbound or tirzepatide, that's basically bumper down the road. So that kind of weight regain, I commonly see in some patients despite the use of tirzepatide. When we start these medications, I do tell them that the use is gonna be one year or more and it has to be combined with diet and exercise, not alone, medications just alone is not going to do any kind of magic. Bringing at that point, I do usually bring into the discussions SURMOUNT-OSA trial and talking to them that how tirzepatide kind of improved the AHI, the apnea-hypopnea index in comparison to just diet and exercise. So when we are looking at tirzepatide, we are looking at a lot of weight loss but if you look at the level of inflammation that was brought down by tirzepatide or Zepbound, so that was kind of very impressive. So we also have to look at the molecular mechanism of action of this drug. Like possibly right now we don't know how it's kind of affecting obstructive sleep apnea treatment so much, we are looking mainly at weight loss but down the road maybe we could come up with some mechanisms which could possibly be affecting inflammation, you know treating inflammation, maybe treating diabetes or treating the carotid parenchyma. So when we're kind of talking about the use of this drug on a long-term basis, I do tell them that it most likely it's gonna be a long-term medication but they have to incorporate some lifestyle changes, diet and exercise. At that point we can discuss more of SURMOUNT-OSA trial than how tirzepatide it lower not just the weight but also the inflammatory markers that also help reduction in OSA events or the AHI index in comparison to just the placebo or diet and exercise. So both arms of that study they incorporated diet exercise but only one arm was able to show such a significant reduction in obstructive sleep apnea. So in my opinion right now I do tell them that this is gonna be a chronic medication and they cannot be expecting such on and off kind of treatment that okay, you take this medication for a few months and then it's treated and then you're off it. So that's not how it works for now. Maybe in future once they lose weight, they have incorporated diet and exercise properly into their lifestyle, maybe they're able to maintain that weight loss and they can stay off the medication. So that could be a possible mechanism but for now I think it's a chronic medication.

Dr. Nadeem:

Thank you, so Fariha as Inderpreet mentioned in terms of treatment is chronic and long-term. When you have your initial discussion after the diagnosis of OSA about what complications come from untreated sleep apnea, what have we seen how CPAP as well as tirzepatide, how did they decrease that complication rate? If you could talk a little bit about that.

Dr. Abbasi-Feinberg:

Of course, you know, in the end we are looking for what are the end results of what we're doing, right? What are the treatment options doing? So yes, I always talk to patients about what we think are the increased risks. So we know that some of them are related to the constant hypoxic burden that patients with obstructive sleep apnea, if it's untreated have, there seems to be a higher risk of cardiovascular disease, hypertension, some cognitive dysfunction, things like that. We know that the frequent awakenings during the night that are associated with it, the sleep fragmentation causes significant daytime sleepiness and that affects quality of life issues. So people have trouble with driving, have trouble at work, have trouble with interpersonal relationships. And so those are sort of the untreated effects that we look at, you know, there's been some debates as to what are the long-term outcomes of treating somebody with CPAP therapy and you know the data that we have is a little bit mixed and we're still trying to sort through now we know that it definitely helps people feel better. That's a definite, we know, that it helps people with blood pressure in terms of cardiovascular risk. We're sort of stratifying the data trying to see does it make a difference if someone has mild sleep apnea or more moderate to severe. And it seems to be that for moderate to severe sleep apnea, it seems to make a difference. For people that have mild sleep apnea, I think we need to look at it a little bit more carefully and so those studies are still ongoing. Yeah, in terms of the question you asked about Zepbound, I don't think we have all of those answers yet. Right, I mean some of this data is fairly new, there's ongoing studies right now that are looking at longer data points and I'm excited to see, you know, where we end up with all of this.

Dr. Nadeem:

Now, that's helpful and that's why like from an endocrine perspective, we have relatively long-term data about GLP-1s in diabetes and then now with obesity. I was curious to know more about the OSA information and I guess we still have a lot to learn the longer these are in the market or these are used. Would also wanna point out like, Inderpreet you mentioned that you have a multidisciplinary group practice where there is endocrinologist and sleep medicine working together. So could you talk a little bit about that?

Dr. Madahar:

So yes, so as we have kind of started seeing more obesity patients for as the, you know, the GLP-1 awareness has been rising in most of the patients. So most of them they're coming, that's when I start screening for obstructive sleep apnea basically. So when they're complaining about fatigue, that's my first go-to question is do you feel tired during the day? So that's when I start screening them with the STOP-BANG or Burden Questionnaire. Those are two main questionnaires that I use. And then I feel like in patients who have BMI more than 35, that's when I commonly start seeing obstructive sleep apnea. And in those cases you'll start seeing that, you know, even you don't need to even go through full STOP-BANG Questionnaire at all. Most of the patients they have full-fledged signs of obstructive sleep apnea and that's when I just usually refer them to Sleep Medicine and they undergo polysomnography or at home sleep study and usually we kind of get the results and that's when I kind of start prescribing tirzepatide. So I hope that's the question you're asking, is that right Dr. Nadeem?

Dr. Nadeem:

Yes, that was helpful and I was trying to understand how like in terms of developing a multidisciplinary way of managing OSA, Fariha also alluded to like, you know, I think as a sleep physician, as an endocrinologist getting those referrals in and coordinating that care, how can we make that better and is there a way we know that, you know, there exists a perfect way to kind of make this happen so that the patient is not waiting to see the sleep doctor and then the endocrinologist and then starting treatment somehow. Like the model where we managed diabetics, we manage, you know, eye disease. We have clinics sometimes where the person can come in and have their foot exam, eye exam and see the endocrinologist and then nutritionist at the same time. So do you foresee a multidisciplinary practice model like this?

Dr. Abbasi-Feinberg:

I would love that if that was accessible for everybody. You know, I think every practice is different and every location is different. So in my practice, the practice that I'm in is mostly primary care and then a handful of specialists. And so I've come up with a program and I'm allowing basically the primary care docs to go ahead and order a sleep study if there is a high probability and the patient is at high risk for having obstructive sleep apnea. And so we have a process where they can put the order in. This patient has a device mailed to them, they have the sleep study done and I can look at the results and then I contact the primary care physician and tell them the results. Then we just, you know, we can discuss what to do. And so that's really sped up the whole process quite a bit. We have to look at programs like that to make sure that we can increase access for our patients because you know, if there's 50 million people that need to be evaluated, you know, there's just not enough of us to be able to do all of this. So coming up with some inventive ways to work through this problem.

Dr. Madahar:

In my practice, yes we do have access to sleep medicine but I feel like as we involve more primary care as the awareness to, you know, we see treatment is rising, we are kind of getting the nurse practitioners, the PAs involved. What we are doing is we are holding monthly sometimes, you know, once in two months lectures for primary care physicians and the NPs, PAs. I think the more we involve primary care, the better screening we can get out of the system. So I don't want the primary care people to just wait for the endocrinology referrals. Usually what I see is they're referred to endocrinology practice for sometimes hypogonadism, sometimes for fatigue. So those are the cases when you start screening for obesity. But then this is the kind of awareness I want the primary care to have. So I think one way we can kind of increase the whole awareness would be possibly through, you know, more webinars, more lectures. So that's what we are doing at our practice and this is the trend that I'm seeing now that most of the patients have already undergone the screening by the time I see them in comparison to what I used to see in the past, the patients would wait for them to see me and then will be referring patients to sleep medicine. So I think that'll bypass my clinic or it won't waste a patient's time to see a sleep medicine physician.

Dr. Nadeem:

I think both of you had a really valuable insight about how you know, education and maybe empowering other members of our team to kind of getting the process started is helpful. And I also wanted to get your thoughts on, Inderpreet on, we see a lot of patients and not just us as endocrinologists but primary care and as well as there are many standalone clinics that are kind of quite busy diagnosing people with low testosterone levels. And I kind of always, that's something where I'm always like if I see a new patient with a hypogonadism low testosterone, you know, doing a full workup, the evaluation of OSA is also very important because untreated sleep apnea and if testosterone treatment is started could actually be harmful. So yes, could you both Fariha and Inderpreet if you can comment on that population, which there's a huge group of people on testosterone replacement, some with the right indications, some unfortunately not because it's unregulated for a little bit. So if you can talk a little bit about that.

Dr. Madahar:

So usually how I explain to my patients would be that testosterone causes the pharyngeal muscle hypertrophy that will cause more congestion in your neck. So if you have untreated obstructive sleep apnea, then it's gonna just make it worse. So testosterone not likely would, you know, help you with your symptoms. It could possibly make you feel more tired and that could worsen the cytosis in all, you know, the complete blood count numbers. In these patient populations, I think the awareness for obstructive sleep apnea, not starting testosterone right away, I think that would be a good step. And possibly the education again and I would say primary care because they're the first kind of go-to people for every patient. So I would not recommend starting testosterone in such patients and just wait so that we can screen them properly.

Dr. Nadeem:

And Fariha, what are your thoughts as a sleep physician? Do you see a lot of patients on testosterone before they've been evaluated for OSA?

Dr. Nadeem:

Dr. Abbasi-Feinberg:

Absolutely yes, I do. You know, there's so many times when somebody presents with, "oh, I'm so tired" and they get treated with something and typically most of my patients will tell me that, you know, it initially seemed to help a little bit, I thought I felt a little bit better and now I'm six months into this and I'm not as good as I'd like to be or you know, I'll hear the, oh, it didn't really help at all type of situation. And that's when they come to me, you know, I definitely see it and like you said, it's difficult for me as a non-endocrinologist to always know was the indication appropriate or not. And you know, I'm not the person who's going to tell the patient that of course, but my job is to evaluate them for what else is going on. And so if they have obstructive sleep apnea, I can definitely help them with that.

Dr. Nadeem:

And so have you seen the dangers I guess because from a sleep medicine perspective we don't see that but like of somebody who may have started testosterone and not been evaluated or not optimally treated for OSA with ending up with complications or with worsening hypoxia?

Dr. Abbasi-Feinberg:

It's hard for me to tell, right because by the time they come to me they're already on their testosterone. So I'm not really doing comparison studies on them. But you know, some of these gentlemen have really pretty enlarged necks and you can just see them struggling to breathe when they're sitting there. Whether that's because of the testosterone or because of their anatomy and physiology already ahead of time. It's really difficult for me to say.

Dr. Nadeem:

Yes, you're right. Well, that would be a great study I think, you know, people going to testosterone low T clinics and kind of doing that, I think that's a great idea probably. Going forward, I know Fariha, you had mentioned that besides tirzepatide, which is currently the only FDA-approved medication for OSA, what are some things in the pipeline that you would like to talk about?

Dr. Abbasi-Feinberg:

Yeah, it's an exciting time to be in sleep medicine. It really is. So there are two medications that are combination of medications that we already have in the system that are being evaluated for sleep apnea. The first one is a combination of atomoxetine and oxybutynin and you would think, well how in the heck would that do anything? But it turns out that there is some way that it affects the neurotransmitters. So norepinephrine and acetylcholine and they all have to do with movement of the tongue and the airway. And so this particular molecule has had the Phase 2 studies and recently Phase 3 study trials results have come out and there actually rather promising depending on what happens over the next, you know, six months I think we're expecting more data that's going to be an exciting avenue for people. The other medication that's out is going to be a combination of acetazolamide and dronabinol. And again, both of these are medications that have been FDA-approved for other indications and somehow this combination seems to help. We think that the acetazolamide is causing a little bit of a metabolic acidosis and that seems to increase respiratory drive and dronabinol targets and binds to cannabinoid receptors and it stimulates airway dilatation. And so again, you know, if you would've asked me 10 years ago, are we ever going to have a pill for sleep apnea? I probably would've, you know, said absolutely not. But here we are. And so, you know, I love that science evolves and we learn things and we try new things and I can't wait to see, you know, what the results of these studies are going to be and it's going to change the way we practice sleep medicine.

Dr. Nadeem:

For sure, exciting times like with new medications coming in. And so that brings me to ask about, so this appears like a multi-pronged approach to management of OSA, right. With tirzepatide targeting sleep and maybe having the central effects which affect it and then the CPAP machine. So do you feel like we would be using all of these in combination going forward?

Dr. Abbasi-Feinberg:

I think it's going to be great to have options available for patients and it's going to take us years to come up with new clinical practice guidelines, right. I mean the American Academy of Sleep Medicine is always looking at best practices and trying to help our membership and help our patients as to what the best order is. And I think it's going to take us a while to sort through everything, you know, right now what we have available seems to be that if you're doing tirzepatide, you should also treat the underlying apnea along the way. And so I often will retest people after they've had a significant weight loss or if they, you know, get to their goal weight or close to their goal weight. I usually have them skip their PAP device for a couple of nights and see how they feel. And if they feel great then it's worthwhile to retest them. You know, if at that point they're still snoring and gasping and their bed partner tells them that they still are not sleeping well then we usually hold off until more weight happens. And it's very much an incentive for patients to see the improvement in their numbers and to see that things are getting better because then they say, okay, I'm gonna keep doing this, I'm gonna keep working on this long term. And you know, of course as you guys all know with the GLP-1s, people don't only just see the weight but they see their metabolic parameters come down so their cholesterol's better, you know, their blood pressure comes down as they lose the weight and they're just overall feeling better, their joints hurt less. And I think all of that seems to help with their sleep as well. You know, so I think the multi-pronged approach works great. It's going to be, you know, partially what is the best multi-pronged approach for which patient. And you know, I think we're finally getting to the point where we can really provide precision personalized care for patients with sleep apnea.

Dr. Nadeem:

Inderpreet, do you have any input about your patients and you know, their feedback since tirzepatide is on board and then looking forward at the newer medications that Fariha just talked about?

Dr. Madahar:

So I have been offering them a Zepbound for obstructive sleep apnea. So I have both sets of patients who have been extremely compliant and who have been non-compliant. I have patients who have lost 100 pounds and have come off of the CPAP machines completely. And then I have patients who have gained weight on, you know, despite being on tirzepatide. So it's more about patient response, how they're complying to diet, exercise and their medication regimen. When I talk to them about the new medications, I do see a lot of medications come on the horizon in terms of GLP-1 and GIP and with the GGGs, I do see a lot of hope coming up. I do see a lot of, you know, right options in terms of medication management for obstructive sleep apnea and not just the CPAP machine. So I think in future endocrinology would be contributing as much to the treatment of sleep apnea as much as we see the sleep physicians are doing. So I feel very confident about that.

Dr. Nadeem:

Great, and I'm curious to know, you mentioned people gaining weight while on tirzepatide, so is that a compliance issue of not taking the medicine or just not being able to tolerate higher doses?

Dr. Madahar:

Very much a compliance issue more than compliance. They are taking the medication expecting that it's gonna keep the weight off while they're not working on their diet and exercise as much. I asked them to, you know, calorie deficit, all these things are very important that, you know, gaining weight while you're on the medication, it could be a kind of a worse sign for their overall management. So I do see compliance more than the dose issue. I think tirzepatide if anything it's tolerated better than what we have seen in any of the GLP-1s in the past. So dose is not as much as an issue, I would say.

Dr. Nadeem:

So I'd like to end with asking both of you and Inderpreet, you can go first about any comments or any anything else you would like to add to the conversation that we've had today about the management of sleep apnea and the role of different modalities for its treatment?

Dr. Madahar:

I would like to involve more primary care, more education for them, you know, so that we can have a broader screening base, lesser burden for specialties. That will be my comment. And then start treatment early, diet and exercise. And of course from endocrinology standpoint, I think we have Zepbound or tirzepatide as a treatment and yes, involvement of a multi-pronged approach, involvement of sleep medicine earlier would be better because if you leave one side unaddressed, the treatment results are not gonna be as good as you would expect.

Dr. Nadeem:

Very helpful, thank you, and Fariha?

Dr. Abbasi-Feinberg:

Yeah, I think I'd like to emphasize that people should not be afraid of being evaluated for sleep apnea. Yes, CPAP devices work wonderful and yes, they're still a mainstay of therapy but there are so many other options available and we really are talking to people and trying to meet them where they are and go from there to come up with the best solution for that patient in that particular circumstance. And I think the future's very bright for treatment of sleep apnea. We have all the things available that we already talked about, but there's some new options that are coming down the line. There's help out there. I think it's surprising to me how many people don't even know that there is a specialty called Sleep Medicine. Probably not amongst your readership but amongst the general public. And so I always put a plug in for, you know, we've got a couple of great websites through the AASM, we've got sleepeducation.org and then we have Sleep is Good medicine, and Sleep is Good Medicine is a public awareness campaign that we're doing which is really geared towards both providers as well as patients. And so I would strongly recommend that your listeners perhaps go and check those out and use some of that information to help their patients.

Dr. Nadeem:

That's very helpful to know. 'cause I think in terms of educating our patients, those are good resources to go to. Thank you so much. So I'd like to end our conversation and thank you so much to our guests, Dr. Abbasi Feinberg and Dr. Madahar for sharing your valuable expertise. Thank you so much.

Dr. Abbasi-Feinberg:

Thank you, it was a pleasure.

Dr. Madahar:

Thank you.

Speaker 1:

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