Virtual Grand Rounds: Pharmacotherapeutic Approach to Obesity Care Part Two

CommonSpirit Health hosted part two of our Grand Rounds series discussing the pharmacotherapeutic approach to obesity care.

See Part One here.

Please find the most up to date guidance on the Medical Management of Obesity here.

Speaker:

• Thu Le, PharmD, Clinical Pharmacist, Dignity Health
• Mahmuda Tasneem, MD, Internal Medicine, Virginia Mason Franciscan Health

Panelist:

• Layla A. Abushamat, MD, MPH, DABOM, Endocrinologist and Assistant Professor, Section of Cardiovascular Research, Baylor College of Medicine
• Anila Chadha, MD, Obesity Medicine Internist, Dignity Health Medical Group – Bakersfield

Transcript

SPEAKER_04 0:04

Welcome everybody. This is part two of pharmacotherapy for obesity, and we're really excited to round out this conversation, and we have many of the same experts back for our discussion, and we'll have a couple of talks, followed by a panel, and I'm excited to hear it. It's such a hot topic and a dynamic topic, so it's good for us to all keep up with the latest. And to help introduce our speakers today, backed by popular demand, Dr. Gary Greensweig. So good to see you, Gary, and why don't I hand it over to you to introduce our speakers today?

SPEAKER_05 0:42

Great. Thank you, Tom, and good morning, everyone. I was thinking two and a half years ago we started this project, and here we are today with the same cast. It's great. All of our speakers were introduced last week, so this will be abbreviated. We have Dr. Mahada Tasmin, who's an internist and also board certified in obesity medicine in the Pacific Northwest. Dr. Tu Lee, who is a uh Pharm D who graduated from the uh University of the Pacific and works part-time at Sequoia Hospital near me here in Northern California. Dr. Abushamant, who is an endocrinologist from the section of cardiovascular research at Baylor, who was with us last week. And last but not least, Dr. Chada, who is a board certified family medicine physician and obesity medicine physician in Bakersfield, California. So with that, I am going to turn this over, I believe, to Dr. Lee.

SPEAKER_02 1:40

So since this is part two of the pharmacotherapeutic approach to obesity care series, we'll just jump right in. There will be two connected presentations given today. And between the two of us, we should have a balanced perspective on when and when not to use obesity pharmacotherapy options. And in addition to presenting theoretical discussions, we're going to try to provide practical solutions. So at the end of this first part, my hope is that we'll gain an understanding of the evidence for treatment of obesity in special populations comprising of individuals with obesity-related complications. Now, there is no contest in regards to effectiveness in terms of average percentage weight loss with newer agents, say trzepatide, compared with older agents like Contrave. But we'll find that in the pharmacotherapeutic approach to obesity, more is not always better. And this recommendation might seem obvious to us, yet it's not lost on me that it can be distracting to have medications with the ability to reduce over 20% of our body weight. Even so, medications that do not meet all of the criteria for treatment continuation, such as inaccessibility or unlikely tolerability based on predisposing conditions, will create barriers that may interrupt medical therapy. So, why is it so important to consider accessibility and tolerability in medication selection? As we know, during weight loss, both adipost mass and lean mass decrease. And during weight regain, lean mass is not increased as much as adipost mass. Therefore, we go through multiple cycles of body weight fluctuation, which induces an unhealthy body composition, and the consequences include insulin resistance and cardiovascular events. This conclusion comes from a 16-year prospective cohort study where body weight fluctuation was associated with mortality. So, how do we keep patients on medicines that are most likely to be accessible and tolerated? That has been the main question in the chat section from part one. And because of the benefit of randomized controlled trial substudies, we have a wealth of data presented here on this slide on which agents to enhance or even resolve obesity-related complications. And due to the supporting data, insurance companies are more likely to cover them. So the rest of the slides dive deeper into these studies outlining the obesity pharmacotherapy that will provide the best outcomes for specific obesity-related diseases. And we'll look at this slide many times over. I think it's obvious, but level A evidence is the highest quality, most reliable medical research. However, in cases where accessibility or tolerability are barriers, we can move to level B evidence or rarely level C evidence. So first we'll cover anti-obesity, pharmacotherapy, or FDA coverage, and prescribing guidelines converge. For those indications, we'll give you a step-by-step play on how to gather evidence for coverage. And these are ASCD risk reduction, MASH, OSA, and diabetes is a given, but included in the guidelines. For reducing major adverse cardiovascular events, the only anti-obesity medicine with demonstrated benefit is semaglutide. Duration of obesity and visceral adiposity are strong predictors of coronary artery disease in epidemiologic studies. In the select RCT, semaglutide 2.4 milligrams resulted in a 20% reduction in adverse cardiovascular outcomes. So cardiovascular death, non-phatal myocardial infarction, and nonfatal stroke in adults with BMI greater than or equal to 27 kilograms per meter squared and established cardiovascular disease without diabetes. This is a visual slide presenting the same information. So in March 2024, the FDA moved to expand the indication for Rogovi to include reduction of the progression of heart problems in patients with established cardiovascular disease, yay, and overweight or obesity with no diabetes. So for everyone's convenience, we thought it was appropriate to include the criteria for prior authorization. There's three slides here, and I have my slide set printed out with four slides on each sheet double-sided for easy reference. The slides will be provided at the end. And the next step would be for us to uh get this added as a dot dot phrase here. So, what evidence do we have for patients with obesity and metabolic dysfunction associated zetohepatitis? In a planned interim analysis of the essence RCT, semaglutide 2.4 milligrams significantly improved liver histology compared with placebo in individuals with biopsy-defined mash and fibrosis stage F2 or F3. This is another scenario where the evidence matches the coverage. In August 2025, the FDA approved a GOVI for the treatment of non-cerrhotic metabolic dysfunction associated the tohepatitis. And again, here are the prior authorization requirements. That the medicine should be prescribed by or with a gastroenterologist or hepatologist. So moving on to individuals with obstructive sleep apnea, trazepatide is the only antiobesity agent with demonstrated benefit. After 52 weeks of treatment in two randomized double-blind placebo-controlled studies of adults without type 2 diabetes, participants who received ZEPBOND experienced a statistically significant and clinically meaningful reduction in events of apnea or hypopnea, as measured by the apnea hypopnea index compared with placebo. And greater proportions of participants treated with ZEPBOND achieved remission or mild obstructive sleep apnea with resolution of symptoms compared to placebo. So this is the third and final obesity pharmacotherapy that is FDA approved for the condition it was studied to treat. At this point, we've covered all the criteria for prior authorizations. It's important to note that the approval of trusepatide for refractive sleep apnea is best recognized in consultation with a sleep specialist. So glucose lowering and cretin hormone therapies need no explanation for the treatment of diabetes in conjunction with obesity. It's worth noting the higher the percentage of weight reduction, the greater the hemoglobin A1C reduction. In this case, more is better. Patients with type 2 diabetes and chronic kidney disease are at high risk for kidney failure. They're at higher risk for cardiovascular events and death. So the flow trial published in May 2024 demonstrated the risk for a primary outcome event of clinically important kidney outcomes and death from cardiovascular causes was 24% lower in patients assigned semaglutide, 1 milligram per week compared to placebo, in patients with type 2 diabetes and chronic kidney disease. And additionally, the rate of kidney function decline over time was significantly slower with semaglutide versus placebo, as tracked by estimated glomerular filtration rate. So this makes semaglutide the treatment of choice in patients with type 2 diabetes and chronic kidney disease, in addition to many of the obesity associated conditions. Now we have to cross the bridge toward obesity-associated indications that are ineligible for coverage, according to the FDA. My colleague will cover what we do for patients that do not have one of the three indications above via the GLP1 bridge program. And just because there's not enough evidence for Medicare coverage does not mean there is not demonstrated benefit for our patients. In pre-diabetes, for example, trzepatide and semaglutide have the potential to prevent progression to type 2 diabetes. The diabetes prevention program demonstrated type 2 diabetes prevention was observed at 10% weight reduction with lifestyle prevention. I'm sorry, lifestyle intervention. And trzepatide and semaglutide meet this criteria. Unfortunately, increan hormone medicines are not FDA approved for pre-diabetes. Hypertension is an obesity-related disease, and one of the benefits of weight reduction is, of course, lowering blood pressure. Like in the treatment of diabetes, the higher the percentage weight reduction, the greater the systolic and diastolic blood pressure reduction. What's interesting is that fentramine on its own is contraindicated with uncontrolled hypertension. However, the combination of pentramine and tapyrimate demonstrated benefit for blood pressure, and a randomized multi-center double-blind study enrolling adults with overweight over obesity, fentramine tapiramate, 15 milligrams and 92 milligrams, reduced systolic blood pressure by 3.2 millimeters of mercury at week eight. Now, on the flip side, now trexone with buproprion is contraindicated in uncontrolled hypertension. Unfortunately, these medicines are not FDA approved for the treatment of hypertension. Now, individuals with obesity and heart failure with preserved ejection fraction display unique features like increased plasma volume and greater cardiac remodeling when compared with individuals with FEFPAF without obesity. In the STEP, HEFPAF RCT, semaglutide 2.4 milligrams significantly improved heart failure-related symptoms and functional limitations and reduced body weight. And this was measured by a change in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, which quantifies heart failure-related symptoms and physical function. So is semaglutide FDA approved for the improvement of heart failure symptoms in HEFPEF? Not yet, although this may change in the future as we learn more about the improvement of heart failure with preserved ejection fraction with obesity treatment. So I'll switch gears to osteoarthritis. Because of the need for randomized controlled trials with a larger population, there are no medicines with level A evidence for the reduction of osteoarthritis pain in obesity, although GLP1 receptor agonists have shown overall promise in reducing both osteoarthritis symptoms and markers associated with disease progression. It's just that variability in pain relief measurements with weight loss in retrospective cohort studies involving semaglutide, terzepitide, and lyrigutide likely influence the low-level evidence available for demonstrating benefit in obesity. And so, as expected, there is not enough evidence for FDA approval of anti-obesity medicines for osteoarthritis. Now, here's something we don't talk about enough, but will likely come across in the treatment of overweight and obesity, and that's binge eating disorder. Binge eating disorder can occur in people of average body weight, but it is more common in people who have obesity, particularly severe obesity. However, it's important to note most people with obesity do not have binge eating disorder. So it's important that we identify these individuals. According to several meta-analyses and reviews, cognitive behavioral therapy, CBT-based approaches are widely considered the most effective intervention for binge eating disorder. For these patients, weight loss pharmacotherapy alone is ineffective and has the propensity to worsen the disorder. And that is because the goal of treatment is to provide relief from the eating disorder, not to lose weight. This is the criteria that we can pay attention to when we're treating a patient with overweight or obesity. And the only medication that overlapped was topiramate. And even then, it is not FDA approved for binge eating disorder due to the short trials, including the medicine. So I'll bring it to a close with some key takeaways. The first part is the best obesity pharmacotherapy is one that will also treat pertinent obesity-related conditions and be accessible and tolerated. The only three obesity-related complications with FDA approval or support for the use of obesity pharmacotherapy are one ASCBD risk reduction, two, metabolic dysfunction associated CFTO hepatitis, and three, obstructive sleep apnea. And lastly, we should be cautious in treating obesity with pharmacotherapy when there are signs of binge eating disorder, because CBT is the first-line treatment for BED.

SPEAKER_00 17:42

So I'm just going to follow up with uh what Dr. Lee just ended. My talk is going to be side effects. As these medications become more and more available, we are going to see millions of patients on these medications. And what do we do as clinicians in the background? What is it that we are going to monitor? That's going to be my focus. My first slide is uh these are my objectives. I just want to review Medicare, uh, the GLP Bridge program quickly and then go over the side effects. So this is a one-page handout I really like, and it comes from the obesity care. If any everybody can use this, it's really helpful. This is an algorithm and it goes systematically. And when when you well, in any point when you stop, your patients are not going to be covered for these medications. Medicare is very, very strict and they follow this criteria. So the first question is do the patients have Medicare Part D or do they have an standalone PDP plan in their Medicare Advantage? If the answer is no to any of this, you can just stop. It's not going to be covered. The next question is the three things that Dr. Lee mentioned. If you have Medicare Part D and you're a diabetic, if you have moderate to severe sleep apnea and if you have MASH, you're not going to qualify for the weight loss part of this bridge therapy. But they do qualify for some of the encryption therapies through their D plan. And so once we get through that question, then we look at their BMI. And the BMI, if it's above 35, and you've documented that the baseline BMI was 35 before initiation of any therapy that they've been on before this start of this bridge program, they still qualify. So that is the good news. And then you need to look at each criteria and figure out what is it that is covered under that. And then actually, if you look at their prior authorization form, it's a three-page form, but it's simple yes and no. And that will either qualify or disqualify your patients. Some things to remember, all four medications, which is your terzepatite Z bound, the Vigo V pill and the injection, and the Fonday or the or frogliprone are all covered for $50. That starts July 1st until December of 2027. So you need to inform your patients. We don't know what will happen after 2027. They may have to pay out of pocket for that. When you look at the ZEP bound, the only thing that is approved is the quick pen. So if you just put ZEP pound and you send the regular pen, you're going to get it's going to bounce back to you. The second thing is make sure that you have an associated diet obesity code, and usually it starts with an E66. That family of codes needs to be associated. Somewhere in your prescription, you have to say send to bridge for weight management. Otherwise, it's going to come back to you. So those are the three important criteria to remember. And then once you once the first approval happens, you don't have to keep doing prior authorization again unless you're switching your medication. At that time, you need to redo it again. And also don't forget they only do it for 30 days. 90 days in this particular program is not allowed. So those are the important factors. So that is about bridge therapy. I do have a slide that shows the prior authorization. I just moved to the end. It's very simple, it's easy. If you can document when you see your patients all the prior authorization questions in the assessment and plan, it makes it going to make your life easy because when it comes back to you, you just have to fill the yes and no questions. My next all my slides after this, I'm really going to focus on the side effects and what caution we need to use while prescribing these medications. On that note, my first uh I think Dr. Lee also talked about weight gain, weight loss, what happens. And sarcopenia is one of these uh things, especially with medications being more available to our elderly population, we need to start paying attention to sarcopenia. So sarcopenia is usually Typically linked with aging, it it can happen to patients with obesity, but can happen to anybody. So, with aging, when you have decreased muscle strength and physical functionality, that is what is sarcopenia. Why is this important? Because it increases it, uh, you know, it increases risk of all-cause mortality, falls, fractures, and overall reduce quality of life. So, prevalence, if you look at sarcopenia in elderly without obesity, it's actually 12% by the age of 60 to 70, and it doubles to 30% in ages 80 and above. So we already all need to be paying attention, anyways. But now with obesity, when you add it together, the risk becomes higher. And if you look at the criteria, so the European group came up with this criteria on how to diagnose sarcopenia and who do we pay attention to. So there are three categories: it's strength, muscle mass, and performance. In the strength, you can use either one of these, it's grip strength and a chair standing and sitting, that we can do in the clinic easily. Muscle mass is actually measured by either by a DEXA scan or a bioelectrical impedance method. And then the performance is gate speed, and then this called the shot physical battery. It's it composes three or three different tests. So the way you diagnose is if one of these categories is positive, it's possible sarcopenia. Two, sarcopenia, three, severe sarcopenia. So these are some quick tests that we can do in our clinic. And I just put this up because this hand grip strength, uh, this is a validated tool. You can get, you know, you can get from Amazon $30 tool too. I don't know how accurate they are, but something is better than nothing. So you can use this, or you can do without any tools, you can just do the stand and sit five times up and down. You can demonstrate it. The patient has to hold their hands above their chest, have to stand up completely and sit down, and then you can use a stopwatch to uh determine how they're doing. And either both of these have uh, you know, they have there's little uh notes that tells you at what age how much you can do, and that is easy to download on Google. This is just a visual slide. So with more encryption therapy and more weight loss, fortunately, what we are finding is when you lose weight, you also lose muscle mass. But so far, what it's turning out is even though they lose muscle mass, the strength seems to be preserved. So that's good news. So most of our patients have low muscle mass with normal strength, so they do fine. But there are few patients that lose the muscle and lose and have low strength. Those are the patients we are going to watch out for because those patients are at high risk for all-cause mortality, faults, and like lifestyle. So, how do we assess for objective physical functions or weakness? Look, if patients are non-ambulatory, are they using any assisted device? Can they rise from a chair without assistance? Can they, you know, how is their walking speed time up and up? How long do they take to move from one place to another? How is their grip strength? We talked about sit and stand instead. Are they reporting self-weakness? Pay attention to that and document that. This is what I do in my clinic, especially in older patients, is look at strength, ask them if they can lift a 10-pound bag, um, difficulty walking across a room and whether they need aids. So this is as each one stands for a thing. So strength, assistance, rise from chair. Are they having difficulty from rising? Climbing, can they climb 10 steps and then falls, number of falls they've had in the last year? And I put the scoring down, it scored from zero to two points in each of these measures. And the interpretation is if it is less than four, the sarcopenia risk is low. But if it's more than four, this indicates sarcopenia, and we need to start paying attention to these patients. So pause before prescribing and ask these questions. The same questions I've gone over is is this patient's having a profound weight loss? Uh, is it coming close to bariatric surgery, the weight loss? And if it is, then we may need to do a DEXA scan to see what their fat-free mass is. Will ask the question will weight loss cause or exacerbate sarcopenia in this patient? Do you have access to interprofessional teams? Because it's kind of come in handy, exercise physical therapists, physical therapists, uh, registered nurse uh thing and care managers. So long always pay attention to long-term consequences. Modifying. So when you notice that the patient may be going towards sarcopenia, stop, monitor. Should you go beyond monitoring should go beyond weight loss. So speed of weight loss is likely important. Are they doing it too rapidly? Do we need to gradually modify the dose? Look for symptoms, fall, lightheadedness, hypertension, do not overlook, need medication adjustment at that time. Be mindful of polypharmacy. Um that was about sarcopenia. And now I want to kind of move on to the other side effects. If you look actually, these medicines, the side effect from this medicine is actually mostly GI side effects. Everything else is a correlation or an association. So I'm I've kind of put it together. Some of them are real side effects, some of them are associations. So I just want to go over this. The first is avoiding pregnancy. The safety profile is actually not known, but the consensus is when patients are taking these medications, we need to avoid pregnancy. So the recommendation is two months before conception, don't take the medication. If you look at terzipatide, it interacts with OCP. So when initiation or dose increase, the ADA recommends second form of contraception at least for until the maintenance dose is reached, or at least for four weeks after every increase. Now, the most common side effect is of course nausea and vomiting. Again, the expert opinion is to have patients take smaller meals, hydrate, avoid fatty foods, avoid prolonged fasting, and extend the dosing intervals may help. I see this very common in my patients, and this is what I've been doing. And usually when I extend the dose, it seems to help and it does resolve. It happens every time you increase the dose. This is just to show that when they did a study between semaglutide and placebo, clearly it had way more GI side effects. So then the other thing is commonly asked as pancreatitis. I have this question, patient uh providers always ask me, my patient had pancreatitis 10 years ago, can I give this? It's not an absolute contraindication. So evidence from long-term randomized control dials does not support a role of these medicines causing pancreatitis. But it is good to look for certain risk factors because those risk factors themselves can cause pancreatitis. And then when we add the medication, the question is can it, you know, can it precipitate pancreatitis? So usually I keep this list. So anybody with obesity is at a high risk, rapid weight loss, history of gallbladder disease, diabetes, hypertriglyceritemia, smoking, alcoholism, and age above 50. And if my patients have multiple core risk uh risk factors, then I just inform them. I'm like, there's a possibility, we just have to monitor it closely and let's go very slowly on the doses. Gastroparesis, again, there's a link, it's not a true side effect. Um, so they did randomize, they looked at all these random, there's no link. But ADA recommends if your patients have gastroparesis, please avoid these medications. Gallstones, again, it's just the link. It doesn't cause it by its own. So then there is this uh thing about acute renal disease. What they've noticed is the medicine itself doesn't cause acute renal disease, but severe dehydration precipitates this. So we have to be kind of watchful. And especially in hot weather, so the risk, how do you mitigate these risks? Slow titration reduces GI side effects and dehydration risk. My main thing is hold and gritin during acute illnesses. Uh, so this is the main thing I tell patients, you know, an adequate hydration during summertime. And then if you need to, and if they're you can always monitor the renal functions. Thyroid cancer. This is one question I get asked a lot. Uh, so it's not a contraindication if your patient has papillary cell thyroid cancer, you can give this medication. The only the the in the you cannot use it in patients with medullary thyroid cancer. Uh, and then I have this question how do you know who has medullary thyroid cancer? Because patients don't know they've had cancer for so long. And one clue is to if your patient is having calcitonin or CEA checked annually, then it's likely medullary cell thyroid cancer. But remember, this is such a rare cancer in any event. And if they have it, the patients will probably know that they have this. Um, the one other important thing is TSH monitoring. TSH is lowered by your GLP therapy. This can reduce levothyroxin dose requirement, potentially leading to iatrogenic thyrotoxicosis. So it's important to monitor TSH more regularly, especially when they are losing much larger amounts of weight. Hyperglycemia, the medicine by itself doesn't cause hypoglycemia, but of course, they're using insulin. I have a lot of diabetic patients that are using both sulfuryl as insulin and when they're in the process of changing. So please be careful because uh hypoglycemia is common in these patients. Procedures. Um, you know, two years ago there was a newsletter that uh the anesthesiology association sent out saying that stop medications two weeks before the procedure. Since then, this more nuanced approach now. The ADA standard of care and JAMA perioperative guidelines all came back recommending a personalized approach with shared decision making. There are certain considerations to be taken when depending on when you want to hold the medications. So if the patient is a diabetic, of course, if you're going to stop at two weeks, you need to make sure that they have some other glycemic control. Symptoms of delayed gastric emptying like nausea, vomiting, distension, and dyspepsia, clearly those patients need longer time. Do not escalate the dose during times before procedures. 24-hour liquid diet before fasting may not be a bad idea. And if you're in doubt, you can always do a perioperative gastric ultrasound before the surgery. Colonoscopy is ongoing, evolving. Meds may increase the risk of inadequate PrEP, and withholding one dose is a good idea. So, like I said, the Oculus 2 is an ongoing trial. We'll hear about it soon. Uh, the conclusion, what we need to do for colonoscopies. This is the other pet peeve hair loss. Uh, quite a lot of patients when on encryption therapy are beginning to have hair loss. So I looked it, I looked it up a little. Two types androgenic alopecia and telugium efluvium, common, women common. Tresipatite, the one that causes the most weight loss, also causes most hair loss. Semaglutide is actually dose-dependent. As long as you keep the dose less than 2 milligrams, apparently there's no hair loss. Um, so rapid weight loss is the main thing. So controlling the weight loss actually helps. So these are preventative strategies. Avoid rapid weight loss, avoid severe calorie restriction, adequate intake of proteins, iron, zinc, vitamin D, vitamin B12, and vitamin A is essential. But remember, the vitamin A, you need to take it at therapeutic levels. If patients are overdosing vitamin A, that itself can cause hair loss. So you have to go over the supplements and find out what it is that they are doing that can cause it. And patients who have gastroparesis, they have the worst hair loss, but they also respond really well to vitamin supplementation. For androgenic allopatia, the only thing that helps is topical monoxidal use for now. Biotin. I have a lot of patients on biotin. All women are, all these influencers are saying biotin is the big thing. And so my patients are taking biotin, and but there's really no high-quality studies supporting biotin use. It's found it's very hard to get biotin deficiency. If patients have biotin deficiency, they respond beautifully with good hair growth if you take biotin. If you don't, then it's not useful. And it's you and it's found in so many foods that's used in the Western diet. Also, it's produced in the intestinal flora. So it's unlikely your patient is going to have this deficiency. And these are some acquired biotin deficiencies. If your patient is eating raw eggs, uh, states of malabsorption, alcoholism, pregnancy, use of antibiotics chronically. So if your patients have some of these risk factors, then you can think about could it be biotin insufficiency. The one slide that I'd like you to all remember about biotin is biotin is is interferes with a lot of commonly used lab work. So the recommendation is the patient needs to stop supplementation at least 48 hours because otherwise you're going to be treating falsely negative or falsely uh positive tests when the patients truly don't have the problem. So this is something I found while I was doing this uh uh this uh study for this test. Ocular complication, uh retinopathy. If your patient has diabetes and retinopathy, the this the rapid uh decrease in hemoglobin A1C seems to aggravate retinopathy. So be careful. And patients should be regularly monitored for complications. So the AGA recommends actually retinopathy status be assessed before encryption therapy because, like I said, it a rapid A1C loss makes it worse. The new one is nion, which is non-arteric anterior ischemic optic neuropathy. Um, when they look, there's there is the hazard ratio. There is no, they are noticing that semaglutide and rezipatite is associated more and more with nion. But if you look at the absolute risk, it actually still remains very, very low. So there are several factors that appear to increase susceptibility to nion in GLP users. So rapid A1C reduction, small cup to disc ratio that is anatomical. Patients have it, age less than 50 male sex smoking history, concurrent vascular risk factors like hypertension, diabetes, uh, sleep apnea, CKD, and amyodorone use. These are just individual risk factors for niaon. So the North American Um Neuro Ophthalmology Society and the American Academy of Ophthalmology, they both came up with a joint consensus statement that there possibly there's an association, but the risk remains very low. They recommend shared decision making with your patients. Okay. Routine ophthalmological screening before initiation of this GLP is not currently recommended. So that is the take-home is yes, there is an association, but if the risk is really low, but still talk to your patients, especially if they have any of these risks, be more mindful of that. These are the last few slides. Heart rate, both these medicines increase heart rate. You don't need to do anything if they're asymptomatic. If they become too symptomatic, then of course you'll have to uh change the medication. Injection site reaction, of course, many injection site. I have hematomas, patients complaining of it. So using longer needles, injecting at 90 degree angle, and using ice before and after seems to help. That is my last slide. Thank you so much for attending.

SPEAKER_04 38:32

That was both amazing presentations. Very thorough, very thorough. Um, do we have any questions in the chat? Well, let me start off, you know, maybe a generic question as a general internist who gets easily overwhelmed. Um if you and maybe Dr. Tasman, maybe this is for you, like of all the things you listed, because I got a little overwhelmed. Get in, like, you know, what are the one or two things that and I'll let others answer this that you really want to focus on as a you know, as a primary care, you know, APP or family medicine or general internist who's going to be prescribing these. Because I I started to get, oh my goodness, now I got to do eye checks and I got to do all these things. And so what would you, and then maybe I'll let the others jump in. Like, what are the two, three things you really want to focus on as you initiate these drugs in in different patients? I think the what's your take, what's your take home?

SPEAKER_00 39:29

You know, that's sort of my my take home, the two questions that I get asked by other clinicians in my clinic is pancreatitis. If the patient had pancreatitis 10 years ago and they had gallbladder disease related pancreatitis, their gallbladder is gone. That is not a contraindication for this in Christian therapy. You can start it. And then the recommendation is if you do have a pancreatitic risk and it's not related to anything, after a year, you can slowly gently start that. That is one thing. And the second question I get asked all the time is thyroid cancer. Who do I start this? Can I start this on patients with papillary? I'm like, yes, you can.

SPEAKER_04 40:06

Well, let me let me let me shift it a little bit from what questions you get, but like what would you recommend a primary care provider focus on as they initiate therapy, given all of the things I just heard? Um, and then maybe I'll pass that on to others. So that's like, okay, those are your two most popular questions. But what if you were if you're not an expert in this and you're initiating therapy, like what would be the two things or you would really want to make sure people focus on? Uh, you know, muscle mass, rapidity of weight loss. Like, what are the two things that you would focus on?

SPEAKER_00 40:41

I think it is going to be on sarcopenia and kind of making sure to to separate patients that are at high risk and monitor them, especially the muscle mass loss. And I think I what I didn't mention is because I didn't uh look at the treatments, you know, what are the treatments like in taking in making sure that they have increased protein intake, also making sure that they're doing resistance training and emphasizing that at every visit is the most if there's one thing I would say water.

SPEAKER_04 41:12

That's what I'm looking for, because I'm a simple country doctor, you know. Yeah, me and Gary are very simple country doctors. Um and uh Dr. Lee, do you agree with that or any any other like hey, take one? If you're gonna if you're gonna remember, remember all these drugs are being prescribed by people that are not experts in this, and that's natural. That's like mental health like prescriptions. And so what do you think about that?

SPEAKER_02 41:35

Um resistance training, yes.

SPEAKER_04 41:38

Um I think in the last session we I get to do that no matter whether I'm taking a medication or not. So that's like a whole, you know, that's you know, but yes, resistance training.

SPEAKER_02 41:47

Yeah, the important part um I remember Dr. Wisdom on the slides last week had a really great introduction to some for everybody. 150 minutes of motor intensity exercise, of course. We talked about that last week, it is recommended. And if we're taking more and more of these medicines, um is it 350 minutes? Isn't recommended a minute? Um to me, that's what 60 minutes, six days a week, and then you get someday enough from whatever activities that you want to do that.

SPEAKER_03 42:24

My two takeaways. First is that this isn't a magic pillar shot that lifestyle is necessary. I think there's a big misconception out there that the shot itself will make you lose weight no matter what you eat. You can eat whatever you want. So that's my number one. Number two is setting expectations between both the provider and the patient about weight loss, um, the weight loss targets per week, so kind of the rate of weight loss. But also what I look at, which isn't actually necessarily the number of pounds or kilos loss, it's more so your other comorbidities and focusing really on the comorbidities in the patient.

SPEAKER_04 43:08

Let's Dr. Chandra.

SPEAKER_01 43:10

Yeah, the the first thing that I look at is how can I make sure that the patient is going to be able to tolerate the medication very well? So how do what guidance do I have to provide to the patient in the first uh meeting that so that they can take this medication long term? And for any new, uh for a primary care who's uh, you know, uh more recently starting uh taking interest in obesity medicine and prescribing these medications, I my recommendation would be that take it slow, do not increase the dose um every four weeks. Just take it up slowly. These are long term medications. There is no risk. And when the patient really has tolerated that dose pretty well, then take it to the next level.

SPEAKER_04 43:58

Yeah. Good, good advice, Gary. I'm just gonna say questions for each other on the panel, please.

SPEAKER_05 44:04

Yeah, right. I mean, I what I heard in all the slides was taken slow.

SPEAKER_04 44:09

Yeah, I like that. See, that's what I'm looking for. You know, you're a busy internist, you're seeing, you know, 20 patients a day. The patient walks in the door, like you know, back to your mind, like, hey, let's go slow here. Um, you know, let's make sure you're this is not a magic pill. You still gotta watch your diet, you still gotta do some exercise. Like those are the basic conceptual ideas that people need to kind of lean into. Um because you know, we all, you know, and then refer to you guys when things are you know tricky or complex and stuff like that. So Gary, I don't know, any questions or any of the questions from the audience?

SPEAKER_05 44:45

Yeah, there there's there's one question which I think um uh is emblematic of what providers face, not just in our own system, but in lots of systems that have these rules. And and and the question is any suggestions for getting our pharmacy benefits manager to approve uh trisepopide or any of these meds for a 68-year-old male with OSA, um, heart failure, diabetes, mellitus type 2, A1C 5.7 on metformin, obesity, BMI 45. He's on CPAP. And and and and I this one specific patient.

SPEAKER_04 45:23

Wow, that was very specific. Uh I thought it was I thought it was like a patient who might have any of the problems. In fact, all of them are not.

SPEAKER_05 45:30

No, I I think this uh requires, and it's not just for our system, but for all systems like this, uh a phone call uh with with your internal head of pharmacy that has a relationship with the benefits managers. One of the challenges we have is that um all of our all of the our big healthcare systems have benefits managers, and so they pay a flat fee, and then the benefits managers have their own rules, and our fee is based on the rules that they have. But but for these kinds of one-offs, I think it's one-to-one conversation with our pharmacy team and then with the benefits manager. I mean, this this is a good thing. I can see I can see Layland.

SPEAKER_03 46:10

I was gonna say, well, I'm gonna say this actually is a great point that I think is frustrating for a lot of people is someone with a normal A1C on treatment for diabetes, which diabetes in this case is not in remission. It's not cured. That's not the definition of diabetes remission or cure. The patient still has diabetes, it's just controlled diabetes. However, there are benefits to treatment with diabetes for diabetes. So I this actually is a something that comes up a lot where insurance companies will deny because of a normal A1C.

SPEAKER_04 46:42

And so I think one of the things I didn't realize the question was basically saying more generically, hey, I've got generic patients with normal A1Cs, but a host of problems that are correlated to their diabetes.

SPEAKER_03 46:56

Yes.

SPEAKER_04 46:56

Medication we know would be beneficial. So I'm getting a rejection to put that together. Okay.

SPEAKER_03 47:02

Now, and and that and that the reason is because this is actually fairly common, especially with all the therapies that we have available to us for patients and um, including for continuity of therapy. So we have patients who get started on GLP1s and their A1C drastically improves. You know, the ADA standards of care actually recommend the treatment of an A1C over 9% with a basal insulin and a GLP1 or GLP1 GIP. And so it is part of now evidence-based medicine to give a GLP1 and it can drastically reduce A1C as we showed today. But I think the key here is actually documentation of A1C at time of diagnosis, what criteria were used for time of diagnosis for insurance companies. Sometimes it's not just documentation, but like you said, also a conversation or a letter that is necessary to point out that this is the patient's trend and that all of these comorbidities are associated with the diabetes. And so this is a treatment of their diabetes.

SPEAKER_01 48:01

That's so good.

SPEAKER_03 48:02

We see that also. We see that also actually when people get to a normal weight as well on GLP1.

SPEAKER_04 48:11

Well, you know, it's an interesting thing.

SPEAKER_03 48:12

Now your mate weight is normal.

SPEAKER_04 48:14

Yeah. I mean, I've always taught diabetes is not hyperglycemia. Diabetes is a systematic disease that you know damages your body in many, many, many ways. And that number you see is only a reflection of it's a surrogate marker for a disease that we have. Um, it's the same thing for AFib. People think AFib is this, you know, little irregular heart. It's actually a condition that affects the entire body. Um, and we get very confused by these numbers uh versus a general condition. So I think that's a great reminder. Any other questions? And so I think go ahead. Sorry, Leila. Well, we have more questions.

SPEAKER_03 48:52

I was just gonna say documentation is oh yeah, we do have a couple. I'm gonna just quickly, documentation is gonna be key here. If someone had a normal A1 or A1C or a normal BMI now on treatment, then you need to document what was their uh A1C or BMI prior to treatment.

SPEAKER_05 49:09

Right.

SPEAKER_04 49:10

Gary, you have more questions there?

SPEAKER_05 49:12

Two short ones. Um, are there any studies that support the use of obesity medications with diabetes type one? Yes or no?

SPEAKER_02 49:22

Yes, yes, there are. There are studies with um lyriglutide, semaglutide, and then there's one with trzepatide that is scheduled to end December 2026.

SPEAKER_03 49:34

Yes, the largest published is adjunct one and adjunct two, and they're referenced in the standards of care this year. And this is actually the first time in the standards of care that it obesity pharmacotherapy was recommended as a level B for people with type one. But with close observation, there are a couple of consensus statements out there that are endorsed by societies, but not one that's endorsed by all societies. But I think that's going to be coming soon as we get more studies that really mentioned.

SPEAKER_05 50:04

Interesting. And the second and probably last one is do you ever leave a patient at the starting GLP one dose longer than four weeks to minimize side effects? Technically, it's not approved or effective for treatment for insurance sometimes, and insurance sometimes won't cover it for longer than four weeks for that reason.

SPEAKER_00 50:24

I have patients on small doses and they do well. Some of them are super responders. There's really no need to go up if they do well on the smallest dose. And remember, until now, it was they had to pay out of pocket. So they had they had a need to keep it low, the cost. So I have sometimes kept them on the smallest dose of uh encryption therapy and added something else, like some other oral medication to kind of keep the thing going. But now with it becoming the GLP bridge therapy, I think patients will want to go up much more.

SPEAKER_04 51:00

Yeah. Yeah. Well, I think that you know, the message, it's kind of fascinating. The you know, how insurance is like, well, your hemoglobin C was normal, so you're gonna get you no longer eligible, or your weight's normal, or you're sitting at this one dosage for too long. We're not gonna so these are all um, you know, sort of roadblocks that we need to be able to overcome, particularly with I like how Gary said, or someone said, you know, really a lot of the work, particularly for busy primary care docs who are not just doing this work, is to kind of go slow, right? And because it's a long, this is a long journey. This is not a quick journey. And with muscle mass is a big concern, particularly in the older patients that we give this to go slow, watch muscle mass, look for stability, gait stability, things. I mean, the the worst thing we want to do is have falls. Yes. And um, that that to me is the number one concern in my mind. As someone who cares for mostly older adult patients with multiple chronic illnesses, the interaction of medications and things to that effect can, you know, fall can be really a big concern.

SPEAKER_00 52:08

So and practically sorry, go for it.

SPEAKER_03 52:12

Oh no, go ahead, Dr.

SPEAKER_00 52:13

So I was just saying practically, you know, nowadays we are seeing patients on video visits. So just I recently saw a patient that had was started on an encryption therapy by somebody else, and I saw her as a video visit. And during that visit, I asked her a question. I said, What dose are you taking? And she couldn't remember. So she had to get out of her chair to go look for the dose. That's when I realized she couldn't get out of the chair that she was sitting in. She was struggling, it took her so long. And I'm like, wait, what? So I had to stop and I said, You have to see me for me to consider.

SPEAKER_04 52:51

That's a good that's a great that's a now that's a great anecdote. Um, well, first of all, we should all we should all tell our patients to get out of their chairs when we're on video conferences just to take a look and see how they they're gate. But that's a great insight into that. Maybe we should wrap it up there. Um, so I think it's a nice little anecdote uh to for people to hang on to as we do this amazing medication that's you know transforming healthcare, but we really need to be thoughtful. We have to go slow, we have to be aware of all the different things that you guys highlighted. Tremendous work. So grateful for the work you guys do. Uh, we're really lucky at Common Spirit to have such amazing leaders who who are focused on this area and educating us and taking care of our patients. So, Gary, do you want to say any last words?

SPEAKER_05 53:33

It's been a long time since I've seen you. Thank you to our attendees and thank you to our panelists for being here, not one but two weeks in a row. Um, I think we really had an in depth uh and educational um time together both last week and this week. So thank you so much.