Obesity Treatment & Safety Save

Hello everyone. Welcome to Tuesday Night Rheumatology. I'm Jack Cush with RoomNow. Tonight we'll be discussing again obesity, specifically, how we treat obesity, what's effective, what are the concerns, what are some of the caveats we need to know, especially as we rheumatologists become more and more familiar with, the many options our patients have. We have an expert panel tonight.

I'm going to ask them to introduce themselves. Let's start with Doctor. Wright.

Thank you, Jack. And it's really such a pleasure to be here with friends and colleagues. I am Grace Wright, Rheumatologist in New York City, right now crowded out by the United Nations. I'm happy to be here doing this today. And I actually practice across the spectrum of inflammatory arthritis, lupus, spent a few decades at NYU Medical Center, and have really had a huge interest in obesity because it's been a very important part of how we deliver holistic care.

So I'm thrilled to be part of this panel for what's going be an exciting discussion.

Doctor. Simenetti.

Hello, everyone. It's great to be here and being here with the panelists, Doctor. Wright and Doctor. Meese. I am an obesity medicine specialist based in Salt Lake City, Utah.

Excellent. And Philip? I am Phil Meese, rheumatologist based in Seattle at Providence Swedish Medical Center, where I direct, rheumatology research. And I'm honored to be on this panel with Grace and Juliana. Grace, I've known for a long time and really love hearing her insights about things deeply rooted in practice.

And Juliana, I've gotten to know recently because I've been helping to lead the GRAPA groups initiative on obesity education. And Juliana really is just a deeply experienced and knowledgeable authority on obesity that we've been learning a lot from. So hope to impart some of that to you this evening.

So I've been surprised in getting into this campaign month on obesity, the obesity imperative. Now, I wanna thank Lilly for being the sponsor of all the education on obesity this past month. But I've been surprised that number one, the many rheumatologists that I've known for years that have really emerged as very thoughtful leaders, teachers, researchers in obesity management, including Philip and Grace and others that you've met during the month. Then the second part has been the absolute treasure of getting to work with many, really incredible, endocrinologists and obesity management specialists who have taught us a tremendous amount about where this field is going and why it is so exciting. I want to thank all of you for tuning into this Tooth Night Rheumatology webinar.

We have one more after this week. We'll talk about that at the end. I wanna encourage you to ask questions. You can do so by clicking on the Q and A box, and we'll answer your questions real time as we discuss matters during this program. Tonight, it's efficacy safety, and you'll see a lot of the different topics.

A lot of our discussion is going to be informed or initiated by a survey we sent out to, rheumatologists yesterday. One time, we had almost 200 responses from 34 countries, 70% from The United States, 83% rheumatology respondents, but, about 7% advanced practice providers, 2% fellows, 8% other doctors. We have other internists and other non rheumatologists. Hopefully, that's endocrinologists and dermatologists who are also tuning in to this program. Please tell your colleagues that they can watch this program either on YouTube or on the RheumNow channel or on any of the social media channels where it's now being live streamed, as we go through the program.

So let's begin with one of our first questions to the audience, which was, pretty straightforward, of these incretin therapies, the GLP-one targeted therapies. They're approved for a lot of different things, all the following except in our audience got it right seventy five percent of the time that PSA is not an indication for GLP-one, but type two diabetes is, sleep apnea is, patients with high cardiovascular risk and risk reduction appears to be. I'm going to throw up another little table here and ask our panelists to talk about indications in use. Juliana, why aren't all these therapies, why don't they not all have the same indication?

Yeah, I think that's a great question. It's just interesting to think on how the clinical research that has been around those medications. We like to think of this as I often get questions like, there's new therapies. I think it's an important reminder that the GLP-one based therapies have been FDA approved for the treatment of diabetes since 2005. What really has changed over the years has been the efficacy of those medications.

It started with the treatment of diabetes and then we saw the patients that were being treated with these medications were also losing weight. I remember that even when I was in my fellowship training, that we were very, unfortunately, we're very excited then and we're very excited now sometimes to give patients a diagnosis of diabetes. So that had also more severe obesity because we saw the effects and how how well they did on those medications. I think what has been really revolutionary over the last few years is the development of those medications being approved for other conditions, such as sleep apnea. And we had some of the discussions last week that this goes way beyond just the weight loss that we do think there's other inflammatory measures that it lowers.

And that's why we do see improvement for cardiovascular disease in particular for prevention of reoccurrence of heart attack and stroke. And we saw that for semaglutide and very large studies, almost 18,000 participants for that. One thing that you don't have written here is also the improvement of fatty liver disease with fibrosis. Semaglutide is now also FDA approved for the treatment of mesh with F2 and F3 fibrosis. And then we have the exciting approaches for tirzepatide on the treatment of sleep apnea and as well as for psoriatic arthritis and something that I'm sure we'll be talking more about it today.

And just thinking general, the GLP-one based therapies work in a similar way, but now we are adding additional incretins and we're finding out that those additional incretins seem to have some maybe added benefits in particular different conditions. We don't know all the answers yet, but we know for what they work for and it's a lot more than just weight loss.

Grace, does this inform the drugs that you choose when you use these in your practice?

Well, helps me sort of, you know, put things in context. But where it helps most is getting the drug approved for the patient. And so I see my patients coming to me who have gone through cardiology. They're going to be on the drug that had the cardiovascular risk reduction. And so that was always Ozempic, that class, maglotide.

But now we see the latest data coming out with tirzepatide that they're also getting that indication. I think as we see this race towards the end for multiple endpoints for each of these drugs, yeah, that's going be important. But it does help me. For instance, I have a patient with a BMI of thirty six, and it turns out that her fatigue from her axSpA was really sort of contaminated by fatigue from sleep apnea. And I was able to get it to her because she has sleep apnea as the primary indication.

So it really helps, number one, helps me think about this patient just outside of the musculoskeletal world to think about their lived experience and help them. So yes, to some extent, but honestly, I think when you look at the data, you see that there's a lot of crossover. And many of these drugs are giving you improvements in many of the same endpoints. So it's whichever drug I can get for that patient, I'm happy to get them on something. And I was just looking today at some of the pipeline therapies coming with triple agonist, you know, different dual combinations.

Very exciting, you know, I'm not ever quitting rheumatology, but boy, there is so much movement here, in Juliana's neck of the woods that I think we can learn from and use for our patients. So yes, if I see somebody with, MAZZLED or obstructive sleep apnea, cardiovascular, I just counseled a patient today who's got a calcium score, a cardiac calcium score that says you've got disease. And so now she's eligible, to be treated. It really helps us think about the multi morbidity and help to choose. But it doesn't necessarily stick me in a lane because it just doesn't work that way from an access standpoint.

Philip, maybe you want to comment on this, but I also want to ask you about this next survey question. When I asked rheumatologists, how comfortable are you at initiating weight loss therapy? You can see it's a big spread here. Twenty six percent are not comfortable or don't look like they're ready to write that prescription yet, although that might change. Whereas there's a third that are somewhat comfortable, that's interesting.

What are you seeing as you talk to more and more rheumatologists?

So a word that I was going to add to the discussion on the first pie there was the adjunctive role that these medicines are playing. It's a long road to get an actual indication to treat psoriatic arthritis or to treat psoriasis. That's a huge investment in lots of patients. But I think we're seeing a rolling out of many studies that are showing the important adjunctive role that these medicines have in helping reach superior outcomes in diseases like psoriatic arthritis. We've already talked in this program about the Together PSA and the Together PSO studies that showed that using tirzepatide together with the execizumab yields better results in both psoriasis as well as all the various domains of psoriatic arthritis and multiple improvements in cardiometabolic outcomes.

So although our audience got it right, that it's not approved for psoriatic arthritis, important to know how well these things are gonna start playing together and in achieving good outcomes. So I think what we're gonna see from that pie on the right hand side is a gradual change because we have almost a, don't wanna use a biblical term, but almost a moral imperative to talk to our patients who are overweight or obese about the potential benefits that they can accrue in control of inflammation, improvement of long term outcomes. And so I think what we'll see, especially once insurances start accepting prescriptions coming from rheumatology, dermatology offices, that we're gonna see a greater comfort. In our office, I work with three APPs, two nurse practitioners and physician assistant. The four of us are a quartet, so to speak in caring for our patients and all of us are really learning on the ground about things like getting approval as Grace just mentioned for in a patient with obstructive sleep apnea or with major adverse cardiovascular issues going on.

And all of these things are going to help our office staff figure out what methods do we have to get approval and then how to optimally combine and counsel patients into the gradual increase in dose that need to do in order for the patient to better tolerate from a GI perspective, some of the side effects that occur with these meds. Even if we don't go through formal certification, on the ground, we're gonna get experience and figure out how to do this.

And Phil, when you say that there's been a shift over time, two years ago, maybe there was one percent who even said, I might. And now what I'm finding as I go around and talk to people is many more are willing to dip their toes in the water. I think largely because of efforts like this. Julianna, you've been really instrumental in teaching me and so many others about how to think about these therapies.

I was just going to add, it's really important to think of the patient as a whole too as they're coming into our clinic space right? And all the complications associated with obesity. So really thinking of screening them like something we often will do in our office is that we screen everybody for, like you mentioned Grace for his sleep apnea, we do like a stop bang questionnaire. And then we also screen them for fatty liver disease, which is a really easy one. Like most of people, if they have EPIC, you can do like the fib four and you can at least start a basic screening for fatty liver disease and really trying to address as many of those issues as possible.

So really, as we're figuring out what medications are FDA approved, and I'm 100 with you, Grace, sometimes it's just playing, you know, we were treating them, but also playing a little bit of the insurance game to see how can we get approval of those medications for our patients where they were paying less and they're getting the added benefits of improvement of glucose control, their hyperlipidemia, their fatty liver disease, obstructive sleep apnea, the rheumatological conditions. Really, we're seeing this overall improvement with many of those medications.

So we have a few questions. Philip, we know there's a really unique relationship between obesity and psoriatic disease, especially in psoriasis. Are the dermatologists dipping their toes in this water? Are they starting to write these prescriptions? Do they have the time to do that?

Where is that going?

So when I do standing on the podium and asking people to raise their hand, I'm seeing in dermatology audiences, slightly more people than a year ago. But not as many as in the rheumatology audiences. And I think rheumatologists just have a little bit more time to be able to talk to them about the safety issues and to counsel patients about how to introduce this therapy. A little bit more time to talk about the pathophysiology and immunology of why it is that these are beneficial in their patients. But I do think that many of the dermatologists that deal with psoriasis are getting it.

They understand that there can be a real beneficial effect. And so maybe it'll end up being the nurse practitioner that's working with the dermatologist that takes the time to do this. And I would encourage dermatology practices to think about this, utilizing the APP group that's in their practice to take the time to use these medicines.

That's interesting because we published during our APP campaign, one bit of news that APPs are taking on a bigger percentage share of prescriptions for the expensive medicines in dermatology. They're writing more of the biologics than the dermatologist, even though their numbers are still less than the dermatologist. I think that's a natural as you point out. Another great question comes from John Tesser in Arizona who talks about the huge challenge of ordering and getting the patients on GLP-1s appeals, managing the drugs and whatnot. Again, this might be a solver role for the APPs, but who wants to address the issue, especially given that there are different indications for the many drugs and it's an evolving moving target?

Managing the prescription and dealing with the appeals can be really problematic. Is that getting any easier, Juliana, or how can we prepare our audience?

Yeah. I think each year with the the new set of insurance as it comes through, I have a nurse that tells me she's going to quit because of the number of prior authorizations that come through and how complicated because they keep on changing their guidelines and the rules. Some might be BMI greater than thirty five with obesity related comorbidity, like it's just so I mean, such a mess and requires so much time and effort. Obviously, in our clinic, have become experts in doing prior authorizations. And obviously, if anyone has access to an obesity medicine specialist, obviously, that is a great resource.

But if not in the clinic, I think also utilizing pharmacy, a lot of pharm techs and pharm Ds like the process that we have now, it kind of goes automatically to our pharmacy group. And then when we need an appeal, then it comes back to us. Really utilizing pharmacists, think is another great option. And I do have, as Philip mentioned, other support staff like nurses or nurse practitioners that do help us with the prior auth, but it has been requiring quite a significant amount of time and effort.

I'd like to get a process tip from Philip and Grace. Do you have one that you can offer the audience?

Yeah, well, I'll tell you, after my first three denials, I figured out why they were denying. There were certain fields that they just wanted to see. So they wanted, you know, starting BMI, not when you put them on the drug, but what's their starting BMI that, you know, would give them this diagnosis? And that wasn't enough. They needed the weight in pounds, and I couldn't give one in the height.

They just needed the numbers because this is clearly a check, check, check. And then I needed to document that they had, you know, they had an exercise and a diet plan. What drugs have they stepped through? I just then created structured data field within my EHR. What was my plan and what was your dose and the outcome and the escalation?

So the starting never changes, and I would just keep adding and updating the weight. And so once I figured that part out, getting the approvals was much easier. But then I also had a dropdown that I created that said overweight or obesity based on the BMI. And what was the obesity related comorbidity? Was it the primary thing?

So for instance, you know, somebody with obstructive sleep apnea, because that has an approval, they wanted that to be the primary thing. Right? So one has to know, number one, what are the primary approvals? If it's somebody with cardiovascular risk, what is the cardiology data to support that there is MACE? It can't just be that, you know, your lipids are high.

So I think for some of them, they're like, well, that's great, but you haven't had a heart attack and you're still alive. So clearly we're not going to do that. But if you have a coronary calcium score or something of that sort. So it was really sort of looking at, as much as I hated this, looking at the denials to say, what did they need to see that I didn't supply and then crafting a process. That has made it much easier.

And then Phil, I'm sure you stumbled into the Medicare bridge and all of the additional things that they needed written into creative process for that too.

Yes. In clinic setting, I would say it's an iterative educational process. So everybody huddles together and we sort of exchange war stories about denials and approvals. And we talk about the cases, what is it that we're trying to accomplish? What is it that we know is within the insurance guidelines versus not?

And then it's a rising boat thing where the MAs, the prior authorization staff person, the clinicians knowing what to put in their EPIC notes. All these things are helping with improving the situation. I agree, though, with Julianna that at the first of the year, things change again and you have to go through all this, it's difficult. But eventually back to John's question, I suspect that what they're doing in Arizona is much the same thing. They have a really strong group of physical nurse practitioners and physician assistants there.

And they're working as teams to learn how to do this and to educate their patients properly.

And maybe just going back to Grace's point too about the importance of having a plan for dietary as well as for physical activity, that you document this but also that you do have a plan either that you utilise some online resources and there's plenty of online resources nowadays that they can, that there's telehealth for nutritional guidance, or that you do give some kind of basic recommendations for patients starting GLP-one based therapies on every clinical trial, they had implemented some basic lifestyle interventions. And I do think that that's really key for also for the patient success. The medications only go so far. We really need to be helping patients modify their behaviour and improve their overall health.

John calls the turn of the year the blizzard in their practice. Get ready, it's coming. There are generations and there's a new way as Grace alluded to of newer therapies that are going to offer new opportunities. I wanted to quickly review, this issue of GLP-1s that have a single target and then those that have more than one target. The question of a single target in creatine therapy is the right answer to semaglutide and liraglutide.

Tirzepatide is shown on the right, is a dual targeted drug going after GLP-one and GIP. Can someone take a stab at or just giving our audience an orientation as to when this started, we had just a single targeted therapy and where this is going? Maybe Juliana, you want to tackle that?

Yeah, sure. With the single target is the GLP-one based receptor therapy. Like I mentioned before, those drugs have been around for a very long time. What has changed is how effective they are and the pharmacokinetics where we can now give a medication once a week versus before we are giving them daily. Lareglutide started where we're giving them daily and now we're on to doing a weekly treatment.

And with the single therapy, think is, just thinking of the difference between GLP and GIP and how the drugs work and thinking of potential side effects is with the GLP based therapies, like we produce native GLP-1s when we do eat in particular carbs, or sometimes even lipids. When we do eat food, it reaches our stomach, reach our intestine, release of incretins, in particular GLP-one stimulates the pancreas and then crosses the blood brain barrier and targets the satiety controls. It makes a lot of sense. I just had nutrition, we should stop eating because I have enough food in my intestines. So therefore it slows down GI motility and induces satiety and that's exactly what the drug does.

It's just in our body gets broken down very quickly and the drugs have bind to the receptors where this is long lasted. Then they figure it out if we added on a GIP to the GLP that we have some added benefits, but the GIP works is slightly different. GLP-one leads to more nausea in the central nervous system. The GIP leads to slightly less nausea. What we see with tirzepatide is that with tirzepatide, it leads to slightly less nausea.

So for the side effect profile, we see less nausea with tirzepatide, less of the GI side effects than what we see with the other GLP ones. And I think with the newer drug therapies that are about to enter the market like the Imilin, I think is the other one, the Kagri SEMA is likely going to get approved this year. Another incretin with another added benefit that maybe has more of a metabolic, more of a breakdown of the fat, the peripheral adipose tissue, the GIP part of tirzepatide seems to have a greater effect in the muscle leading to decrease in lipid accumulation within the muscle tissue. So the more that we're adding, we're figuring out that there's some added benefits, they all work kind of in a similar way, but there are added benefits to the dual or the triple agonist treatment approaches.

Juliana, could you speak to the oral agent?

Yeah, so the oralistat, I kind of joke and I usually said I only prescribe oralistat for patients that I don't like because of terrible drug. It causes fatty diarrhea, it has been around for a very long time and leads to very small amounts of weight loss. There is also some of the older agents that we have been using for many years now, phentermine, one of the oldest agents, which is a stimulant and what it does, it decreases appetite. Then you combine that with the pyrimate, so then it decreases cravings and then decreases appetite, that dual effect. The combined medication is sold here in The US as Qsymia.

Oftentimes I might prescribe phentermine in the morning and topiramate in the afternoon or the evening, one to help decrease appetite, the other one to help decrease cravings. Other medications that have been FDA approved for the treatment of obesity. The other one is called Contrave, which is a combination of Wellbutrin and Naltrexone. And again, with the same idea, decreasing appetite and decreasing cravings. And those are cheaper, right?

I mean, phentermine, patients can get phentermine for like $25 week, maybe a month, sorry.

How about the new GLP-one receptor agonist that's oral? And how do you position that?

Oh, the

oral ones, the first one that was approved was Wegovy, the oral Wegovy. The oral Wegovy is the exact same molecule, is the GLP-one receptor agonist is a hormone. However, as we all know, to be able to give a hormone orally is very hard, right? Because it gets broken down in the stomach by stomach acids. But what company, what Novo had done was developed this lipophilic layer around the pill that makes it where patients are able to take it orally and absorb this hormone.

The issue with that is when we're taking it orally is that it has to be on an empty stomach, a minimal of six hours on an empty stomach. And it has to be taken with four ounces of water, cannot be too much and cannot be too little. And then patients have to wait on average of a half an hour to then be able to eat or take other pills. Initially, I thought this was going be a bigger deal. My patients would not be willing to do this and so many patients are able and willing to take that particular medication.

The effectiveness, it seems should be just as effective injection around 15 to 17% weight loss with the oral Wegovy. Now, Orfrogliptron is a non peptide small molecule. So is a synthetic molecule that binds to the receptors, not a hormone base. The easy part of that is that you can take it any time of the day. However, the effectiveness, it seems to be less effective than the other medications around twelve point six percent of effectiveness for weight loss.

So I tend to use that is slightly less frequent because it's less effective. But for some patients, might be much easier where, a lot of my patients take levothyroxine or other drugs that they do have to take it on an empty stomach. So the orforglipron becomes a great option. The other benefit of being on the oral agents is that they are cheaper, right? When we're talking about cost and being one of the biggest factors that affect and how we are choosing those drugs or what patients can take it and for how long they can take it, being able to take a medication that's cheaper, that is very effective, think is great.

It starts at 150 and then it goes up to around $250 to $300 as you increase the doses.

There's Thank more coming in drug development. That's interesting. What do we expect to see approved anytime in the near future? Are they all going be in 2027, Juliana?

I think this year. We're going to have CabriSema, which is the semaglutide plus an amylin. It should be approved by the end of this year, should absolutely be approved. Retatrotide, if I can say that quickly, the triple agonist. That's GLP, GIP, and glucagon, the added glucagon.

The weight loss for the triple agonist is really the data is so impressive. We're really reaching like equivalent of bariatric surgery amounts of weight loss. But with that is that think the discussions around our obesity conferences is how much weight is really great, is more better in the sense that does that lead to better effects? Or are we going to see more consequences as patients might be losing more weight and leading to more sarcopenia, bone or other complications that we might start to see long term?

When we ask this question about what gives you more durable weight loss, it's also magnitude of weight loss and more durable. The audience got it right that it looks like the bariatric approach is more durable than any of the newer therapies that are out there right now. Although, again, that may be challenged by the new triple therapy going forward. But with all the buzz on incretin therapies and marketing and whatnot, especially on the internet, which is compounding problems. I had two reports this week on RheumNow that said that the numbers, mean, bariatric surgery in the last two-four years is down by thirty-forty percent, while the prescriptions for GLP-one related therapies are up like over one hundred and forty-one hundred and fifty percent.

Yet, one report cited that less than one percent of people who are eligible for bariatric surgery are going that route. Are we missing an opportunity here by not encouraging bariatric surgery? Who wants to tackle that?

Well, I've had quite a few patients who went through bariatric surgery. So these are rheumatology patients who met all the qualifications. And it was a process, you know, of the psychological training, the diet, the exercise, going through the program, getting on the schedule, getting the approvals, getting an incretin therapy approved turns out to be much easier. But the problem now fifteen, twenty years later, is for many of those patients have regained a significant amount of weight. And so for some of them, they were able to if there was a sleeve, they could do all these adjustments, but they couldn't then go and have a second and third bariatric.

And what they have done is turned to, incretin therapy, to give them now the benefit. So I think durability depends on when you measure it and in whom this was done. So for me, it's a mixed bag.

Yeah, and that is a concern that I've seen as well with my patients. Again, the numbers who have their durability is good, but the numbers who really have very long term maintenance Sorry of their

to interrupt here, Jack. I just want to say that the longest running study for bariatric bariatric surgery is like the Swedish obesity study that have looked at like thousands of patients that have had bariatric surgery and how well did they do over time. Bariatric surgery is still kind of the golden standard and is still very effective and very durable for the majority of patients knowing that there are some patients that will regain the way back. Some of the things we have done in our clinic and some of the studies that I do run is on genetics of obesity and taking into account that there's different reasons why patients do not lose weight post bariatric surgery. And we have found that many of those that come to see us for medical care post bariatric surgery might have some genetic mutations that make it harder for them to sustain their weight loss.

Then they tend to do better with incretin. So we're hoping with technology and advances too, that we are going to have better recommendations for those patients as more individualized recommendations. And I think we need to take that all into account when we're seeing patients in clinic is maybe bariatric surgery is a better fit for some, maybe it's not for others, but it's still a very good, reliable and long term weight loss very effective weight loss tool.

Philip, when you're balancing patients on weight loss and weighing bariatric surgery versus medical. Is it that medical therapy is your starting therapy? Doesn't even have to be GLP-one. Medical management weight loss has quite a range of things including non pharmacologic measures. Where are you putting that on your list?

So we are, these days talking mostly about diet, exercise, and then the pharmacotherapy approaches. However, if a patient is over forty BMI, then that's one that we typically would refer to a weight loss specialist. And that's where most of the conversation about bariatric surgery comes up. You're right that it is more durable. Once it's there, it's there and has long lasting effect.

And if you end up stopping the incretin therapy, there's a tendency to regain weight, maybe half or two thirds, up to two thirds of what you had, where you were before. So it is a long term commitment to go on these medicines. But now that we're understanding this as a disease and not as a syndrome or just a simple comorbidity, but a true disease that needs to be tackled in the same way that diabetes does, that heart disease does, that rheumatoid arthritis does, then I think people understand, okay, I'm not quite sure what I'm going to be on five years from now, but I'm committed to this as an ongoing

practice. I want to go back, again to incretin therapies. I didn't ask a question about this, but it often comes up when you achieve your goal. Then what do you do? You know, I know this is the big issue with the payment and the cost on healthcare.

Do we maintain people on these drugs? Do we get into micro dosing? Do we acknowledge and support self dosing? There's a lot of issues around this. I don't have a clear feel on where this is going.

Julianna, what's the talk in endocrine and obesity conferences?

Yeah, so what we do know and the data has shown both for semaglutide and tirzepatide is when you do stop medications that you're going to see some percentage of weight regain, it tends to be around seven percent, although they didn't follow them, you know, for prolonged periods of time to really know long term what happens. Currently, you know, we are treating obesity as we're treating any other chronic disease, as Phil just said, that, you know, we don't stop treatment because someone has gotten better, we don't stop treatment for their diabetes or their hypertension, if they have gotten better with that, do have to continue obesity is a chronic disease, we do have to continue to put kind of suppression on their, you know, biological underlining issues as we would with any other condition. So for now, what we do know is that if you stop, you're going to regain. So we do recommend that the patients continue on, how do we do it is a different story. We don't have great data to guide us on how we do, even though they paid on tirzepatide, Eli Lilly has published recent data on transitioning patients from tirzepatide injectable tirzepatide into that orfroglipron, which is the oral medication that we just talked about and saw that they were able to maintain the way off.

So I think the way we're looking at it is that maybe more acutely we give some of the stronger medications, the injectables, and as patients reached a certain amount of weight, like the weight maintenance phase where they're really plateauing in or they reach their target that we start, I either start backing off on the dose or that I will switch them into oral agent. And I worry even more with some of my older patient population or patients that have other complications and limited mobility, like how much are they, are they losing more muscle mass or is there other things that we should be worried about where we should not be losing as much weight? So that's some of the approaches we have been taking, but I definitely think we need more data. And I think more will come as the years go on with the treatments of obesity in this transitioning potentially to oral in lower, you know, maybe not as strong of of a medication as you would do with the injectables.

I'm trying not that my patients really get it, and they they they end up managing it in in ingenious ways themselves. And some of that has to do with lowering the dose. It's becomes more slightly more affordable, and then, and maintaining. But they they really want to maintain where they've gotten to, and men and and they seem to know how to do that properly.

And they have different cues. You know, patients talk to me about the food noise and they can tell sort of once they've gotten to, let's say, BMI of twenty two, where they're smack in the middle of the safety zone, is the term that they use, that rather than doing it weekly, maybe I can do it every ten days. And if the food noise comes back, I take it right away because I know what that's going to lead to, which is interesting to just hear the language that was being used around this.

Racist is amazing. I heard that exact phrase from a patient for the first time today.

Yeah, it's who knows? And I was like, what is that? You know, and they're like, it's that voice in my head telling me I need the cookie when I know I don't need a cookie. And so some of that self management comes from them understanding their own patient reported outcome of food noise. And so now I talk to patients about food noise and I talk to them about the various cravings and the other things.

Some will also notice that their craving for alcohol has decreased or they're craving for smoking, right? As I used to do four cigarettes a month, now I'm down to one or none. And if I see that come back, I know something has switched. So I find it really interesting to have that conversation because at the end of the day, thirty years from now, I want people to be able to self govern, whether it's with our therapies or cognitive behavioral therapies or various other things. But you have to learn to listen to, you know, the signals the body gives.

They're all doing it a little differently is what I find, but they've figured out the outcome that they're tracking.

I was just going to say we definitely need more data. People are doing in different ways and I do a would love micro dosing study to look in particular patients that have inflammation with a lower BMI, what is an effective dose? The truth is we don't know. Usually I do approach patients saying, there are certain things we don't know and this is what I think is safe and this is how pharmacokinetics work. I usually recommend against going like more than seven days because their dose starts and to then they'll take the medication again.

They tend to have a lot more side effects if they extended the timing in that they were taking the medication versus what's recommended. So I really say I would recommend someone lowering the dose and taking a lower dose than extend the amount of time that they go in between dosages.

Can each of you quickly give me a red flag on when to stop incretin therapy? Phillip, do you have one where you tell patients? I learned surgery. You have to be off prior to surgery, prior to receiving general anesthesia because of delayed gastric emptying. Are there other situations where we need to have red flag warnings?

Well, for me, one of them is diarrhea and volume depletion because everybody just assumed it was like, I just had a GI bug, but you can't have a GI bug every month. And so it was really paying attention to the GI side effects. So if now I have this issue where I'm getting volume contraction from that, either we switch, we lower, but we have to do something different. That's clear. I think that was a very easy one to see.

Yeah, I'm with you 100% Grace on that thinking of the concerns of dehydration. And then gallbladder disease, we are seeing higher rates of gallstones. So I just had a patient this last week, she went to the local urgent care twice was sent back home. And without them doing a full ultrasound of her gallbladder, and she had, you know, cholecystitis ended up in the like having surgery, but just reminding patients if they have abnormal, like, you know, feeling a little queasy and some abdominal cramping is very different than having abdominal pain. If they have abdominal pain and nausea that they cannot tolerate fluids or food, then they need to stop the medication and be assessed by a physician or a provider in general.

It's also a rich flag before you start, because I've also discovered gallstones in patients who I'm evaluating for inputing therapy who had no idea that what they were feeling was actually cholelithiasis. So I think it's something to think about at every step of the way.

And pearl the there is that something we do from the obesity medicine perspective is that if patients are losing more than 10 pounds per month, they should be on Ursadiol twice daily until their weight loss slows down because it does increase their risk of having gallstones.

You said Ursadial? That's interesting. What can you do as a new prescriber of these drugs to minimize the GI side effects, the nausea, the queasiness, the delayed gastric emptying, the constipation, whatever? Is it just as simple as choosing the right drug and starting low and going slow? Are there other smarter, small meals, less meals?

I certainly do start low and go slow and really check-in with the patient on a pretty frequent basis to help counsel them, less fatty foods. I do think that smaller portions, making sure that you've got adequate protein, lots of liquids. These are all things that I think are practical useful. I'm also running into some patients who are normal weight, who have gotten compounded drug and by various means. And I'm finding myself being a little concerned about the whole sarcopenia issue, especially in that group.

And we end up counseling against use of the therapy, if they seem to have a history of an eating disorder. I'm very cautious around those folks. With overweight patient group who haven't been used to going to the gym and doing resistance therapy, this is something that we need to get them in with a physical therapist, and actually have them trained, in techniques of muscle improvement, resistance therapy.

Yeah. So this is one of the questions we ask. What's the biggest concern with rapid weight loss, whether it's in creatine therapy or not? Sarcopenia is a major problem, and one often not discovered until it's too late by both the patient and or the prescriber. How do you head that off at the past?

One, an exercise plan, increased protein intake, anything else that we should be doing there?

Yeah, no, I think those are the key, it has to be part of your treatment planning, your treatment approach. The other things that we do do in clinic whenever possible is using like a bi impedance scale, or if you have access to a DEXA scan where you can measure their lean muscle mass before they start treatment and as they continue. The other thing that sometimes I will also check is the prealbumin, just looking at their protein intake and making sure they're having adequate protein intake. In general, as we lose weight, average about 25% of whatever we lose is from lean muscle mass. So what I tell patients, the real goal here is to prevent additional lean muscle mass loss in particular with our older patient population, or as Phil said, a lot of our patients that have rheumatological conditions might not be able to move as much.

I really worry about those patients. So I sometimes will start even with, you know, I have like a sheet that I give for chair exercises, we have bands in the clinic that you know, and those are cheap and easy for them to use. Those are some really basic things, but they have I said, if you want to be on this medication, you have to do resistance training. This has to be part of your treatment approach. Because patients feel fuller sooner with the medication, cannot, we recommend not skipping meals, making sure that maybe they will use a protein supplement like a protein shake if they don't feel like eating.

That's easy and is everywhere now they can, you know, do one of the protein shakes that gives them at least around 30 grams of protein. We usually recommend 20 to 30 grams of protein per meal and maybe an additional snack in between. But obviously, those targets have to be individualized and evaluated and I give to our patients that they're come to visit us in clinic their target protein intake. And fiber can help with constipation, hydration fiber. But oftentimes I'll also put them on a stool softener, give them MiraLAX, Metamucil and MiraLAX as needed.

Bone loss is a surprising issue We asked our audience what drives the mechanism and it appears that it's just pure and simple mechanical unloading. There isn't a direct toxic effect of these agents on bone per se. It's not vitamin D mediated, but what are you guys doing far as Grace, as far as assessing bone loss in these people? Is it really just the people at highest risk that you're worried about or is it everybody?

Well, I mean, have learned to now think about everybody because the group that causes me the greatest concern is my peri and postmenopausal because for me, it's a double risk. And for many of these women, that's when their weight gain occurred and now they really sort of want to lose that extra weight. And I've seen some cross from osteopenia to osteoporosis and not require therapy. So I focus a lot on this with the resistance training and all of the things that we would emphasize for osteoporosis care. I've also seen it though in some of my younger patients with significant inflammatory disease restricting their ability to exercise is to get them into a physical therapy program that allows them to maintain and gain muscle strength.

Because at some point we're going to end up having to deal with the osteoporosis that's ensuing.

John Tesser talks about creatine supplementation. Reasonable or baddish?

Depends on your kidney function, right?

Yeah. Even though I think the data around creatine and I have changed my mind around creatine from before, right? So when I did training, I remember very vividly having patients being admitted, you know, with like bodybuilders that had taken too much creatine an hour and renal failure, but the data, I think if you limit to around three to five grams of creatine per day, actually does seem to have some positive effects. So I think obviously as long as we're following guidelines and following the recommended amount based on what they had done in studies, and you know, I think it's likely okay. The other thing with bone is really thinking of nutrition and nutritional intake, making sure they're taking, they have enough calcium and then vitamin D, right?

We see higher rates of vitamin D deficiency, in particular with patients with obesity since it's fat soluble. I see almost in everyone like I measure vitamin D on the patients that come into our clinic. So we do have to make the appropriate recommendations. And then I start doing a much better job in screening everybody before doing the DEXA whenever appropriate. I definitely worry more with the older population.

And as Grace mentioned, those in the post menopausal period since they have higher rates of bone loss to start with. So that's the patient population that I worry more about bone loss.

Okay, so what obesity treatment has the greatest safety concern? The right answer here is online compounded GLP-1RAs. If you're not following this information, I had a report I think on yesterday from Stanford about this. It's a bit of a problem because it's unregulated. These all come part of a 50 B program, which is there's a list that they can take drugs and compound them and all that was well fine and cool during a shortage situation.

But that was long ago. We're not in a shortage situation anymore. There's legislation currently in process that supposed to prevent this from happening. But this is 7,000,000 up to 7,000,000 Americans are taking compounded GLP ones over the Internet. And this is like what you see advertised on television is just as much compounded stuff as actual prescription stuff.

How are you guys safeguarding against this?

I just say flat out right. You know, I have no control over your safety or outcomes. And what I've also found is that people aren't being properly counseled, of the risks and the various strategies that we just talked about. But the question I always go back to is why are people resorting to this? And many times it's because of cost.

It's because they cannot find a doctor to prescribe it for them. That, for me, is the number one thing that I just hear in the supermarket, you know, around town. It's like, can't get my doctor. My BMI is forty three and they will not refer me to somebody and I can't find an endocrinologist who has an open slot for, you know, twelve months. So we've got to we've got to attack this problem from the root, right, to say, how do we get better access?

How do we get better education so that everybody will be able to find somebody who can do this safely and properly for them?

Agree, right?

Go ahead. No, no,

I was going to say it's just to me so interesting in thinking of stigma and bias around obesity, right? That we don't go get our rheumatological meds or cardiology meds from a nail salon. But now for obesity, we are seeing this differently that we can get it from anywhere. I had a patient the other day getting from Timu, probably not the safest place. I do understand with grace, I absolutely understand where patients are coming from, they are desperate to get a medication that's effective, that will help solve many of their problems.

And they're hearing all of this on the internet and how wonderful it is. And they can afford it even sometimes now that the prices have lower even $150 might be too much for some of our patients.

But

I often say we do not know where it's coming from. We have seen increased cases. And if you look at the FDA over the last few years, I've seen increased reports of overdosing just the way that they mix the medications. We've seen higher rates of infection. You're taking something that we don't know where it has been, how sterile it is, and now we're injecting under our skin.

I know that there have been quite a few cases of people ended up in the ICU with organ failure. The list goes on. There was a report the last week too from the wire. And I think if you all have a chance to watch it, just they sent those medications to check for purity and how many of them did not have at all any of the compounds that they had. Right there, you might be paying for something that you don't, we don't even know what it is.

Yeah.

Philip? In our practice, number one is cost. But the second, which I alluded to earlier, are the normal weight individuals who feel that they're going to be more super people by using this type of medication, reducing cardiovascular risk. Maybe they have a undifferentiated autoimmune syndrome, and they feel that that's going to be improved by using these. So that's the group that I'm very concerned about and am advising against use when I'm worried, especially about they're getting sarcopenia.

You know, I'm amazed how many times this summer I have advised people one about compounding and two about not being offered these therapies by your primary care, by your doctor who you think is saving your life with it's sort of like, no, it's actually indicated for all these other things that you're a prime candidate for and you don't need to be obese to weigh in. Asked a question about integrating care. Can we manage the arthritis and the rheumatology part and the obesity part? I think this may be the real role of rheumatologists to say when these drugs are to be needed. And if you're comfortable, then you do it.

If you're not, you know who to call to get it done. I think that's very important that coordinated care is what patients are going to need.

Yeah, I think everybody has to have a Ghostbuster in their back pocket. You have to have that team that you can turn to for collaborative care, regardless of what the other issue is that impacts our patients. Because at the end of the day, I'm the champion for the well-being of that person in front of me.

Think my staff made a T shirt about me once that said something like, ask me, everybody else is guessing. I want to be the Ghostbuster for people as Grace indicates. Anyway, I want to remind our audience that we have one more Tuesday night rheumatology next week, more than meds. We'll be talking to patients, people who advise patients. We'll be talking to rheumatologists who are running obesity clinics.

I think it's going to be a really interesting, session. I want to thank our panelists for, their excellent advice and superb insights tonight. I'll give each of you a concluding statement. Philip.

Jack, I really appreciate your focusing in on this this month. This has been a zeitgeist topic for all of us. And I feel like we are all learning a lot and really treating our patients in a more holistic way by incorporating the investigation about the patients, their weight, their inflammation, their cardio metabolic factors, and integrating all this. And they trust us. We generally have long term relationships with our rheumatology patients.

And I think that they really look to us for sound advice. So I appreciate your having us focus on this this month.

Grace.

So again, I echo that and just say this is fantastic because what thinking about obesity and various weight categories helped highlight for both myself, my staff, and my patients was that it's not just the skin and joints or the kidney or the lungs, but it forced us all to think about their liver, their sleep apnea, their degenerative arthritis, all of the other weight related comorbidities. That now having that conversation about holistic, wholesome care, sort of treating to wellness became so much easier because this was a door opener for that. And so I really encourage everyone to sort of shift the way we think about this. This is a human with multiple domains, and we have the ability to be impactful across their spectrum. So thank you, Jack, for doing this.

Juliana.

Yeah, no, Grace and Phil has been such an honor to be part of this and to really expand the care of patients with obesity for so long. They have suffered so much stigma and bias in particular within the medical community. So really approaching them in this more holistic way I think makes a lot of sense. And the only other word I'll say I'm here for that call in case anyone needs it. I'm here, I'm here.

I'm also making sure that we're working teams that we do consult one another, that we are utilizing all the tools that we have there, our registered dietitians, exercise physiologists, physical therapists. It really takes a whole village to take care of our patients and all of the specialties to make sure we're not only helping them lose their weight or improve their joints, but we're really helping them improve their lives. Thank you.

Thanks so much for a grand session. We'll do it again next week.

Thank you.