TNR: Obesity Treatment & Safety

Hello everyone. Welcome to Tuesday night rheumatology. I'm Jack Cush with RheumNow. 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.

So we have an expert panel tonight. I'm going to ask them to introduce themselves. Let's start with Dr. Wright. Thank you, Jack. And it's really such a pleasure to be here with friends and colleagues. I am Grace Wright, a rheumatologist in New York City — right now crowded out by the United Nations. I'm happy to be here doing this today. I actually practice across the spectrum of inflammatory arthritis, lupus — you know, 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. It's going to be an exciting discussion.

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

Excellent. And Philip — I am Phil Mi. I'm a 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 GRAPPA group's 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. I want to 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 I've known for years 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. And 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.

So I want to thank all of you for tuning in to this Tuesday night rheumatology webinar. We have one more after this week — we'll talk about that at the end. I want to encourage you to ask questions; you can do so by clicking on the Q&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. At 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. So 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 livestreamed 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-1 targeted therapies — they're approved for a lot of different things. All the following except — and our audience got it right 75% of the time — that PsA is not an indication for GLP-1. But type 2 diabetes is, sleep apnea is, patients with high cardiovascular risk and risk reduction appears to be as well.

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 all have the same indication? Yeah, I think that's a great question. It's just interesting to think on how the clinical research has been around those medications. So we like to think of this — I often get questions like, oh, these new therapies — I think it's an important reminder that the GLP-1 based therapies have been FDA approved for the treatment of diabetes since 2005, and what really has changed over the years has been the efficacy of those medications. We started — 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 — [laughter] — 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 well they did on those medications. And 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 in 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. We saw that — semaglutide is now also FDA approved for the treatment of MASH with F2 and F3 fibrosis. And then we have the exciting approaches for tirzepatide on the treatment of sleep apnea, as well as for psoriatic arthritis — and something that I'm sure we'll be talking more about today. And just thinking in general, the GLP-1 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. And we don't know all the answers yet, but we know 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, it helps me sort of put things in context, but where it helps most is getting the drug approved for the patient, right? And so I see my patients coming to me who've gone through cardiology — they're going to be on the drug that had the cardiovascular risk reduction, and so that was always the semaglutide class, but now we see the latest data coming out with tirzepatide that they're also getting that indication. So I think as we see this race towards the end for multiple endpoints for each of these drugs, yeah, that's going to be important.

But it does help me — for instance, I have a patient with a BMI of 36, and it turns out that her fatigue from her axial disease was really sort of contaminated by fatigue from sleep apnea, and I was able to get it for her because she has sleep apnea as the primary indication. So it really helps — number one, it 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. And 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 agonists, different dual combinations. So very exciting. And 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 MASLD 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 multimorbidity 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 ask 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 kind of 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 and 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.
You know, we've already talked in this program about the TOGETHER PsA and the TOGETHER PsO studies that showed that using tirzepatide together with ixekizumab 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, it's important to know how well these things are going to start playing together in achieving good outcomes.

So I think what we're going to see in that pie on the right-hand side is a gradual change, because we have almost — I don't want to 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 and dermatology offices, is that we're going to see a greater comfort in our office.

I work with three APPs — two nurse practitioners and a 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 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 we have to get approval and then how to optimally combine and counsel patients into the gradual increase in dose that you 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. We're going to — even if we don't go through formal certification — on the ground we're going to 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 1% who even said, "Ah, 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. And I think largely because of efforts like this. And Juliana, you've been really instrumental in teaching me and so many others about how to think about these therapies.

Yeah. And 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 — something we often will do in our office is that we screen everybody for, like you mentioned Grace, sleep apnea. We do a STOP-BANG questionnaire, and then we also screen them for fatty liver disease, which is a really easy one. Like, most people — if they have Epic — you can do a FIB-4 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, 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, the obstructive sleep apnea, the rheumatological condition. So really we're seeing this overall improvement with many of those medications.

So we have a few questions. Phillip, we know there's a really unique relationship between obesity and psoriatic disease, and especially in psoriasis. Are the dermatologists dipping their toes in this as well? 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 I would have 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, you know, utilizing the APP group that's in their practice to take the
time to use these medicines. You know, that's interesting because we published during our 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 dermatologists, even though their numbers are still less than the dermatologists. So I think that's natural, as you point out.

Another great question comes from John Tesser in Arizona, who talked about the huge challenge of ordering and getting patients on GLP-1s — appeals, you know, managing the drugs and whatnot. Again, this might be somewhat of a 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 you know each year with the new insurance, the new set of insurances that 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 it is, because they keep changing their guidelines and the rules, right? Some might be BMI greater than 35 with an obesity-related comorbid — like, it's just such a mess and requires so much time and effort. Obviously in our clinic we have become experts in doing prior authorizations, and obviously if anyone has access to an obesity medicine specialist, that is a great resource. But if not, in the clinic I think also utilizing pharmacy — a lot of pharm techs and PharmDs — like, the process that we have now kind of goes automatically to our pharmacy group, and then when we need an appeal it comes back to us. So really utilizing pharmacists I 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. They wanted, you know, starting BMI — not when you put them on the drug, but what's their starting BMI that would give them this diagnosis. And that wasn't enough. They needed the weight in pounds, and the height. They just needed the numbers, because this is clearly a check, check. And then I needed to document that they had, you know, had an exercise and a diet plan. What drugs have they stepped through? And I then created structured data fields within my EHR — what was my plan, what was the dose, the outcome, and the escalation. So your starting BMI never changes and I would just keep adding and updating the weight. Once I figured that part out, getting the approvals was much easier. But then I also had a drop-down that I created that said overweight or obesity based on the BMI, and what was the obesity-related comorbidity, and was it the primary thing. So for instance, 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 data — it can't just be that your lipids are high. And 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, and that has made it much easier. And then, Phil, you know, I'm sure you stumbled into the Medicare bridge and all of the additional things that they needed written in to create a process for that, too.

Yes. In our 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 tide thing, where 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 Juliana that at the first of the year, when things change again —
and you have to go through all this it it's it's it's difficult but eventually back to John's question I I suspect that what they they're doing in Arizona is much the same thing they have a really strong group of physical uh nurse practitioners and physician assistants there and they're working as teams uh to uh learn how how to do this and to educate their patients uh properly and and I and maybe just going back to Grace's point too about the importance of having a plan for dietary as well as um for physical activity you know that you document this but also that you do have a plan either that you utilize some online resources and there's plenty of online resources nowadays that they can that there's telehealth for for nutrition additional guidance um or that you do give some kind of basic recommendations for patients starting GLP-1 uh 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 right the medications only go so far um we really need to be helping patients modify their behavior and and improve their overall health so John calls the turn of the year uh the blizzard in their practice. So get ready, it's coming.

So um there, you know, there are generations and there's a new wave as Grace alluded to of of newer therapies that are going to offer newer opportunities. I wanted [clears throat] to quickly review um this issue of you know um GLP-1s that have a sort of single target and then those that have more than one target. So the question of a single-targeted incretin therapy the right answer is semaglutide and liraglutide. Um tirzepatide is shown on the right is a dual targeted drug going after GLP-1 and GIP. Um can someone take a stab at or just giving our audience an orientation uh 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. So with the single um you know single target is a GLP-1 based receptor um therapy and u like I mentioned before those drugs have been around for a very long time. What has changed is how effective they are and the you know how the pharmacokinetics where we can now give a medication once a week versus before we are giving them daily. You know, liraglutide started, we're we're giving them daily. Um, and now we are on to doing a a weekly uh treatment.

Um and with the single therapy I think is you know 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 um or sometimes even lipids when we do eat food it reaches our stomach reaches our intestine release of incretins in particular GLP-1 it stimulates the pancreas and and um crosses the blood-brain barrier and you know and u 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 um GI motility and induces satiety and that's exactly what the drug does is just in our body gets broken down very quickly and the drugs have bind to the receptors where this is long lasting.

Um then they they figured out if we added on a GIP to the GLP that we have some added benefits. Um but the GIP works is slightly different. GLP-1 leads to more nausea in the central nervous system. The GIP leads to slightly less nausea. So what we see with tirzepatide is that um with tirzepatide it leads to slightly less nausea. So for the side effect profile um we see less less nausea with their appetite less of the GI side effects that what we see with the other GLP-1s and I think with the newer drug therapies that are about to enter the market like the Amylin I think is the other one the Cagrisema is likely going to get approved this year. Another incretin with another added benefit that maybe has more of a metabolic make more of a breakdown of of the fat um the peripheral adipose tissue. The GIP part of tirzepatide seems to have a greater effect in the muscle leading to decrease in in lipid accumulation within the muscle tissue. So the more that we're adding we're 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 to the dual or the triple um agonist um treatment approaches.

Juliana, could you speak to the oral agent that?

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

How about the new GLP-1 receptor agonist that's oral, and how do you — on the Ozempic? Yeah, yeah. So for the oral ones — so the first one that was approved was Rybelsus, the oral Rybelsus. So the oral Rybelsus is the exact same molecule, you know, is the GLP-1 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 the 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 minimum of 6 hours on an empty stomach — and it has to be taken with 4 ounces of water. It 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. So initially I thought this was going to 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 to be just as effective as the injection, around 15 to 17% weight loss with the oral Rybelsus.

Now Orforglipron is a non-peptide molecule, so it is a synthetic molecule that binds to the receptor, is not hormone-based. 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 12.6% effectiveness for weight loss. So I tend to use that slightly less frequently because it's less effective. But for some patients it might be much easier, where — you know, a lot of my patients take levothyroxine or other drugs that they do have to take on an empty stomach. So 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 how we are choosing those drugs, or what patients can take and for how long they can take it. Being able to take a medication that's cheaper and that is very effective — I think that's great. It starts at $150 and then it goes up to around $250 to $300 as you increase the doses.

Okay. Well, thank you. Yeah. And there's more coming in drug development — that's kind of interesting. What do we expect to see approved anytime in the near future, or are they all going to be in 2027?

Juliana, I think this year we're going to have CagriSema, which is the semaglutide plus cagrilintide. It should be approved — I think by the end of this year it should absolutely be approved. And retatrutide, if I can say that correctly — the triple agonist. So that's GLP-1, GIP, and glucagon — the added glucagon. So the weight loss for the triple agonist — the data is so impressive, right, that we're really reaching like the equivalent of bariatric surgery amount of weight loss. But with that, you know, I think the discussions around our obesity conferences is: how much weight loss is really great, right? 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.

So 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 you know, 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 — I mean, bariatric surgery in the last two to four years is down by 30 to 40%, while the prescriptions for GLP-1-related therapies are up like over 140 to 150%. Yet one report cited that less than 1% 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, you know, it — 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 15, 20 years later is for many of those patients they've 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 turn to 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. I — 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, you know, maintenance of their weight. Go ahead. Sorry to interrupt here, Jack. I just want to say that the longest running study for bariatric surgery is like the Swedish obesity study that have looked at like thousands of patients that have had bariatric surgery and how well do they do over time and bariatric surgery is still kind of the gold standard and is still very effective and very durable for the majority of patients knowing that there are some patients that will regain the weight 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 and they tend to do better with incretin. So we're hoping right with technology and advances too that we are going to have better recommendations for those patients — more individualized recommendations — and I think we need to take that all into account when we're seeing patients in clinic. 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, very effective weight loss tool.

Right. So, Philip, when you're bouncing patients on weight loss and weighing bariatric surgery versus medical — is it that medical therapy is your starting therapy? And it doesn't even have to be GLP-1; medical management of weight loss has quite a range of things including non-pharmacologic measures. So 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 40 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 at maybe half or two-thirds of what you had lost 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? And this is the big issue with the payment and the cost on health care. Do we maintain people on these drugs? Do we get into microdosing? Do we acknowledge and support self-dosing? There's a lot of issues around this. I don't know. I don't have a clear feel on where this is going. Juliana, what's the talk in endocrine and obesity conferences?

Yeah. So, you know what we do know and the data has shown — both for semaglutide and tirzepatide — is when you do stop medications you're going to see some percentage of weight regain. It tends to be around 7%, although they didn't follow them 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 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 — we do have to continue. Obesity is a chronic disease, we do have to continue to put kind of suppression on their underlying biological 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 the patients continue on. How we do it is a different story. We don't have great data to guide us on how we do it, even though — you know — Eli Lilly has published recent data on transitioning patients from tirzepatide injectable tirzepatide into the orforglipron, which is the oral medication that we just talked about, and saw that they were able to maintain the weight loss. 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 reach a certain amount of weight loss — like the weight maintenance phase where they're really plateauing, or they reach their target — that I either start backing off on the dose or that I will switch them to an 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 — you know — are they losing more muscle mass, or are 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 and in transitioning potentially to oral and lower — you know, maybe not as strong of a medication as you would do with the injectables.

I'm finding that my patients really get it and they end up managing it in ingenious ways themselves, and some of that has to do with lowering the dose — it becomes slightly more affordable. And maintaining, but they really want to maintain where they've gotten to, and many — they seem to know how to do that properly and they have different cues. You know, a patient talked to me about the food noise and they can tell sort of once they've gotten to, let's say, a BMI of 22 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 10 days, and if the food noise comes back, I take it right away because I know what that's going to lead to. Which was interesting to just hear the language that was being used around this.

That is amazing. I heard that exact phrase from a patient for the first time today. Yeah, it's food noise 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." [laughter]

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 their craving for smoking, right? As in, 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, 30 years from now, I want people to be able to self-govern — whether it's with a therapist or cognitive behavioral therapies or various other things — but you have to learn to listen to the signals the body gives. So they're all doing it a little differently is what I find, but they've figured out the outcome that they're tracking.

And I was just going to say we definitely need more data, right? People are doing it in different ways, and I would love to do — when you talk about micro-dosing — I would love to do a micro-dosing study to look at particular patients that have inflammation with a lower BMI: what is an effective dose? The truth is we don't know. So usually I 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. So I usually recommend against going more than seven days, because their dose starts to decrease and then they'll take the medication again, so they tend to have a lot more side effects if they extend the timing in which they are taking the medication versus what's recommended. So I really say I would recommend someone lowering the dose and taking a lower dose rather than extending 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? Bill, do you have one? You know — 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, you know, 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, you know, 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, um either we switch, we lower, but we have to do something different. So, so that's clear. Um 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 uh gallbladder disease we are seeing. Yeah, we are seeing higher rates of gallstones. Um so I just had a patient this last week. She went to a local urgent care twice was sent back home um without them doing a full ultrasound of her gallbladder and she had you know cholecystitis ended up 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 um and nausea that they cannot tolerate fluids or food um then they they need to stop the medication and be assessed by a physician or a provider in general.

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

Yeah. Oh, and the other pearl 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 Urso twice daily until their weight loss slows down because it does increase their risk of having um gallstones. And you said Urso. Okay, that's interesting.

Well, 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? Or are there other smarter approaches — small meals, less meals?

So I certainly do start low and go slow and really um check in with the patient uh on a pretty frequent basis uh to help counsel them — less fatty foods. I do think that smaller portions, uh making sure that you've got adequate protein, lots of liquids, uh 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 uh by various means. And I'm finding myself being a little uh concerned about the whole sarcopenia issue especially in that group. Uh and we end up counseling against uh use of the therapy if they especially if they seem to have a history of an eating disorder. Uh I'm very cautious around those folks. With the overweight patient group who haven't been used to uh going to the gym and doing resistance therapy, this is something that we need to get them in with a physical therapist uh and actually have them trained uh in techniques of muscle improvement, uh resistance therapy.

Yeah. So this is one of the questions we ask. What's the biggest concern with rapid weight loss? Whether it's incretin therapy or not. Um sarcopenia is a major problem and one often not discovered until it's too late by both the patient and or the prescriber. So how do you head that off at the pass? Uh one — an exercise plan, increase protein intake. Anything else that we should be doing there?

Yeah. No, I think those are the key — like it has to be part of your treatment plan and your treatment approach. The other things that we do do in clinic whenever possible is um using like a bioimpedance um scale or if you have access to a DEXA scan where you can measure um their lean muscle mass before they start treatment and as they continue. The other thing that sometimes I will also check is the prealbumin uh just looking at their protein intake and making sure they're having adequate protein intake.

Um you know in general as we lose weight on 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. Um I really worry about those patients. So I sometimes will start even with um you know I have like a sheet that I give for chair exercises. We have bands in the clinic and those are cheap and easy for them to use. Um 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.
And because patients feel fuller sooner with a medication, they cannot — you know, we recommend not skipping meals. Making sure that maybe they'll 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 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, you know, Metamucil.

What about bone loss? Bone loss is a surprising issue here. 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 as far — 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, I have learned to now think about everybody, because the group that causes me the greatest concern is my peri- and post-menopausal patients, 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 now 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 — 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 bad-ish? Depends on your kidney function, right? Yeah. [laughter] Even though I think the data around creatine — I have changed my mind around creatine from before. So when I did training I remember very vividly having patients being admitted, you know, like bodybuilders that had taken too much creatine and were in renal failure. But the data — I think if you limit to around 3 to 5 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 have done in studies, I think it's likely okay.

The other thing with bone is really thinking of nutrition and nutritional intake. Making sure they have enough calcium and then vitamin D. We see higher rates of vitamin D deficiency in particular with patients with obesity since it's fat soluble. I measure vitamin D on the patients that come into our clinic so we do have the ability to make the appropriate recommendations, and then I start doing a much better job in screening everybody for doing the DEXAs 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 for bone loss.

Okay. So what obesity treatment has the greatest safety concern? The right answer here is online compounded GLP-1 RAs. 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 as part of a 503B program, which is a list from which they can take drugs and compound them — and all that was well and fine during a shortage situation, but that was long ago. We're not in a shortage situation anymore. And there's legislation currently in process that is supposed to prevent this from happening. But this is — you know — up to 7 million Americans are taking compounded GLP-1s over the internet, and 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, you know, I have no control over your safety or your outcomes. And what I've also found is that people aren't being properly counseled on 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 I can't get my doctor. My BMI is 43 and they will not refer me to somebody and I can't find an endocrinologist who has an open slot for you know 12 months. Um so we've got to — it's 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. Agree.

No, no, you're — I was going to say it's just to me so interesting um in thinking of stigma and bias around obesity, right? That we don't go get our — we don't go get our rheumatological meds or cardiology meds from a nail salon, right? But now for obesity it is a — is a different — we are seeing this differently that we can get it from anywhere. Um I had a patient the other day getting from Temu, right? Probably not the safest place. And 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 lowered — even $150 might be too much for some of our patients. Um but I am — I often say we do not know where it's coming from. We have seen increased um 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. Um we've seen higher rates of infection — right, 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. Um I know that there have been you know quite a few cases of people ending up in the ICU with organ failure. Like the list goes on. There was a report last week too from the wire and I think you know if you all have a chance to watch it — just they sent those medications to check for purity and how — you know many of them did not have at all any of the compounds that they say they had. So right, you might be paying for something — we don't even know what it is.

So yeah, Philip, in our practice it's number one is cost, but the second — which I've alluded to earlier — are the normal weight individuals who feel that they're going to be more super people by uh using uh this type of medication, uh reducing cardiovascular risk. Maybe they have a you know 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 um — when I'm worried especially about them getting sarcopenic. You know, I'm — 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 — and and 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.

Um, asked a question about integrating care — um can we manage uh uh the arthritis and the rheumatology part and the obesity part? I think this may be the real role of the rheumatologist 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 um to get it done. I think it's very important that coordinated care is what patients are going to need.

Um yeah, I think everybody has to have a Ghostbuster in their back pocket, right? 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. You know, I think my staff made a t-shirt about me once that said something like um — ask me, everybody else is guessing. Yeah, I want to be the Ghostbuster for people as Grace indicates.

Um so 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, um 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 uh session. I want to thank our panelists for uh their excellent advice and superb insights tonight.

Um 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 uh treating our patients in a more holistic way uh by incorporating these uh — the investigation about the patients, their weight, their inflammation, their cardiometabolic factors and integrating all this — and they trust us. Mhm. We generally have long-term relationships with our rheumatology uh patients and
uh I I think that they really look to us for sound advice. So I I I I appreciate you're having us focus on this this month, Grace. So again, I echo that and just say this is fantastic because what uh thinking about obesity and 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, uh all of the other weight related comorbidities. So 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. Um and so I really you know 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 and Juliana.

Yeah. You know Grace and Phil this has been such an honor to be part of this um 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 I'm here for that call in case anyone needs it uh you know the the ghost — I'm here. I'm here. [laughter]

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

All right everyone thanks so much for a grand session. We'll do it again next week. Thank you. Thank you. Take care.