Beyond the Hype: Why People Stop Taking Weight Loss Medications That Work with Tim Garvey

Jim Hill:

Welcome to Weight Loss And, where we delve into the world of weight loss. I'm Jim Hill.

Holly Wyatt:

And I'm Holly Wyatt. We're both dedicated to helping you lose weight, keep it off, and live your best life while you're doing it.

Jim Hill:

Indeed, we now realize successful weight loss combines the science and art of medicine, knowing what to do and why you will do it.

Holly Wyatt:

Yes, the “And” allows us to talk about all the other stuff that makes your journey so much bigger, better, and exciting.

Jim Hill:

Ready for the “And” factor?

Holly Wyatt:

Let's dive in.

Jim Hill:

Here we go. Holly, today we're diving into one of the biggest shifts in obesity treatment. We're going to revisit the weight loss medications.

Holly Wyatt:

Yeah, Jim, we've talked about these before, but I think it deserves multiple podcasts because these medications have really changed the game when it comes to obesity treatment. This is one of the biggest things we've seen in a long time in our field. And people are jumping on board with these medications in record numbers. But now I think we're starting to see something interesting.

Holly Wyatt:

A lot of them are starting the medications and then they're stopping the medications. So let's talk about what is happening. What does it mean for the future of obesity treatment? How do we deal with this?

Jim Hill:

Holly that's exactly what we're unpacking today. And we brought in the perfect guest to help us make sense of all this, Dr. Tim Garvey. Now, Tim is our colleague here at UAB. He's an endocrinologist and he is professor of nutrition and medicine. He is really one of the top experts in the world in this area. He's been involved in clinical trials of all these drugs and even the next generation of drugs that's coming along. So, he is the perfect person to help us unpack this. Tim, welcome to Weight Loss And.

Tim Garvey:

Thank you very much for inviting me. It's really a pleasure for me to be here and to talk to your audience and to chat with you guys.

Holly Wyatt:

Yeah. So, Tim, let's start with what you're seeing right now. I know you're in the thick of this in terms of clinical trials, and really, this is what you see on a daily basis. So, what are you seeing? we know these medications work we have great data on that we've talked about that on our show before but we're also seeing like I said surprising numbers of people that stop taking them what's going on? What's your take on this?

Tim Garvey:

Yeah, this is definitely the case, and this occurs in real-world care. We have a lot of clinical databases at different medical centers around the world, really. You know, people lose their weight. It might take a year. It might take a little longer, but then they just stop taking these medications. And, you know, I think it's multifactorial. I mean, everybody's different. Everybody with the disease, everybody living with obesity is different. And the reasons for discontinuation of medicines are different. too.

Jim Hill:

So Tim, start by telling us how the medications work. Holly and I've said this before, but go through it. The idea, they work when you take them. They're not fixing a problem permanently.

Tim Garvey:

No. With this disease, I mean, there's a dysregulation of the way satiety factors interact with feeding centers in the brain, and it's reset to generate and sustain a high level of adiposity, a high level of fat mass in the body. And that's just wired in to the disease. And the body will protect that fat unless something intervenes. And that's what these medicines do. They increase the action of these satiety hormones and suppress appetite. So people lose weight because they don't have the appetite that they used to have. So there's less caloric intake and there's more weight loss. Now, if you stop taking these medicines, of course, those pathophysiological mechanisms are still in place and they work overtime, in fact, to regain that weight. This is what our patients have to fight against. It's not their fault if they regain this weight. I mean, they're fighting against some very powerful biology that's driving this weight regain. So the medicines just stop this process when you're taking them. Once you stop taking them, everything goes back to the way it was.

Holly Wyatt:

Yeah.

Jim Hill:

They're approved for long-term use, right? So there's no problem with people. I mean, we take a lot of other medications. We take permanently blood pressure and diabetes. And that's the way sort of these are intended, right?

Tim Garvey:

Right. I mean, we think our patients are continuing to take the blood pressure medicine.

Jim Hill:

Right.

Tim Garvey:

But I think this particularly applies to obesity medicines. Because after a year, over 50% of people have stopped taking them. And that's what the best medicine, what I call first generation medicines, only 20, 30% are continue to take them. So people just stop taking these medicines.

Jim Hill:

And what do we know about what happens when they stop taking them?

Tim Garvey:

Well, clearly there's weight regain unless people have learned some skills in terms of moderating their lifestyle, you know, watching what they eat and maintaining an exercise regimen, just kind of watching their weight and keeping it down. Some people can do that. Most people can't if you go by what's in the literature.

Jim Hill:

My gosh, Holly, he's talking about lifestyle in a positive way here.

Holly Wyatt:

I know.

Jim Hill:

This is amazing.

Holly Wyatt:

Tim, you're coming over to our side a little bit. I feel it. I feel it happening.

Tim Garvey:

This is being commercialized too. I mean, this is being recognized as a problem. People lose weight with these second-generation medicines, the GLP-1 receptor agonists. They get a lot of weight off. They stop taking the medicines. Then what? So companies are stepping in, developing structured lifestyle programs to try to keep that weight off. I think this is a great development.

Holly Wyatt:

Yeah, so you talked about the first-generation weight-loss drugs, and I think that's a good point to make. You know, these aren't the first medications we've had for obesity. We've had weight loss medications that have been approved and produced weight loss for many, many years. What's different about these medications and why have they changed the field in a way that the other medications, the first generation medications didn't?

Tim Garvey:

Yeah. You know, I mentioned I'm an endocrinologist. I was a very happy diabetes doctor for all of my career.

Tim Garvey:

And then I just happened to do a clinical trial with a medicine called phentermine topiramate. The brand name is Qsymia. And this was 12 years ago. And I just saw people losing 20 pounds and 30 pounds. I said, wow, I haven't seen this in medicine before. I thought we could help so many people with these medicines. But at that time, nobody thought obesity was a disease. I think there's little insurance coverage now. There was very little then because health systems and large employers and coverers, insurers thought this was a lifestyle choice and they didn't want to pay for care. Patients should just go and get their life in order. So we really didn't understand the disease. And there was no clear path where drug companies could develop medicines and make a profit on these medicines. That's kind of sadly where we were just not that long ago. So to answer your question, I think two things are afoot. One is we gradually learn more about obesity. We learn that it is a disease. We learn more about the underlying pathophysiology. We learn more how it's connected to complications and related diseases that really is what impair the quality of life of patients and it can infer morbidity and mortality. So that's one thing, just a better understanding. Two, the first generation medicines on average in clinical trials lost less than 10% body weight.

The second-generation medicines, semaglutide to tirzepatide, they lose 15% or more. And that extra weight loss, that is sufficient to treat and prevent a broad array of obesity complications. So they're good for patients, they're health-promoting, and they're very effective. So I think we have better medicines in a situation where we understand the disease better. And I just think those two things have combined to kind of accelerate rational care, evidence-based care for patients.

Jim Hill:

Tim, the other thing I think to point out about these meds is they're actually helping people reach or nearly reach their goals. We were out promoting 5% and 10% weight losses, improving health, but the patients weren't buying it. They wanted 20%. And now these medications are helping some people reach those goals.

Tim Garvey:

That's true. I mean, you know, if you're an obesity doctor, and you guys know this, and Holly knows this, what the patient wants out of treatment is often different from what the doctor wants out of treatment.

Jim Hill:

Yes, yes.

Holly Wyatt:

Yeah.

Tim Garvey:

I mean, the patient might want to lose an X amount of weight. Maybe they want to feel better. They want to have increased mobility. They might want to look better. Those things are good too, but the doctor also wants to promote health. And to prevent these and treat these complications that they say really would hurt people.

Holly Wyatt:

I always say the doctors were happy. I was happy. We could see this metabolic changes, but our patients weren't that happy. The health piece of this drives some people. That's motivation, some motivation. But there's a bigger motivation, I think, by how you look and feel. And for some people, it takes more than that 5% to 10%. That wasn't enough to really get them into, okay, I can feel this weight loss that I've had impacting my life in multiple ways, including health, but not just about health. And as physicians, we really focus on health because that's what we're trained to do.

Tim Garvey:

Yeah. I think I call it harmonization of the goal of treatment. You know, we really have to pay attention to what the patient wants. I mean, that's why they're there. And then they have to understand the impact of excess adiposity on health. We work together and establish some goals together. Well, these second-generation medicines can often meet both goals, the goals of the patient, like Holly just said, and the goals of the doctor in terms of promoting health.

Jim Hill:

Yeah, that's amazing. Tim, Holly and I have, as you know, we approach this from lifestyle. And one of the things that we've always talked about is that getting the weight off is different than keeping the weight off. And in most of our lifestyle programs, we've tried to do both. But the problem is people never got an amount of weight loss that they were ready to go into weight loss maintenance. So when I look at these meds, and one of the things that we started doing, Tim, and I'd love your response to this, we ask people that are starting the meds, what's your long-term plan? And the answer is they don't have one. They have not thought beyond weight loss. So to me, we need to give people options. And I will tell you, I'm totally fine with going on the meds and staying on them forever, if that's okay. But as we know, not everybody does that. So we need other options. Those other options can be lifestyle. They can be a combination playing around with the lifestyle and some of the first generation or lifestyle and intermittent use. To me, this is the exciting thing that we're finally focusing on weight loss maintenance.

Tim Garvey:

I mean, that's the name of the game right now. We have effective medicines, but how do we keep the weight off for a decade or two decades or three decades? This is a chronic disease. It lasts a lifetime in essence. And those mechanisms that are generating and sustaining a high level of adiposity are always at work. Lifestyle doesn't change that either.

Jim Hill:

Right.

Tim Garvey:

Gives patients tools to deal with. So medications still are going to have a role. But what's clear is that the medications we use in the acute phase of weight loss to get people down to some target are going to be different than the medications patients may take for the next decade or two.

Holly Wyatt:

So what are you seeing? What are some of the reasons you're seeing? I know there's multiple ones that you're seeing people are stopping these drugs that have been successful. Some people aren't successful in the drugs. I think that's one important thing to say. Not everybody loses weight, but there's a good amount of people who lose a good chunk of weight, but not everybody. But those who are successful, what are the reasons they stop? It would seem kind of, why would I stop something that's working?

Tim Garvey:

Cost and access are the most obvious answer. And that certainly plays a role in many patients. But I think it's a little bit more nuanced than that with many patients. I think, you know, these are very powerful anorectic medications and patients lose a lot of weight. And we're seeing they lose too much weight sometimes. It's not healthy. And so patients tend to develop what I call a fatigue syndrome. They feel restless, They're tired. Even their cognition, they think, is not as sharp as it was. They don't have the energy they used to have. We have to worry about nutrition also in these patients in terms of getting the right nutrients in, protein, iron, calcium in particular. And so, you know, they don't feel good. And that's one reason they want to stop medicines. They just want to feel better. They want to feel like they used to. And on top of that, many patients don't have an appetite. So they've lost the joy of eating and the joy of food and the socialization that goes with that. They don't like that. It's not good for their quality of life. So those are some of the reasons, too, patients stop taking this. And so many patients now are on submaximal doses of these medicines because we'll practice because they don't need all of that weight loss to reach the health goals that we need.

Holly Wyatt:

I think that's an important point. One strategy to use is you may maximize the dosage for the weight loss and then pull the dosage down to a lower level for maintenance. Is that something you're seeing?

Tim Garvey:

Well, yeah, but we don't see these drugs. It's only been approved in the last three years. And so we don't have a long-term experience with them. And that's part of the problem. We don't have data to work with in terms of what's the best maintenance program for using these drugs. And now these companies are building into their clinical trial program a strategy where they use a high dose to get patients down to a low equilibrium body weight. And then they get switched over to the lowest dose of the medicine to see how that works to maintain weight over a longer period of time. And all of the companies are doing that. And I think that'll be really valuable clinical information for us. We don't have those answers yet, so we'll see.

Holly Wyatt:

I think it's ironic that people want to lose weight to improve their quality of life, basically, right? That a lot of times that's a big motivator, some aspect of the quality of their life. But then for some people being on these medications actually doesn't improve the quality of their life for the reasons you just talked about. So I think that is really, really an interesting thing to think about and to understand more about.

Jim Hill:

It's a great move forward, Tim, to think about a different medication strategy for weight loss maintenance, because early on the companies were resistant to that. And it just makes total, total sense that what you need to do to get the weight off is different than to keep it off. There's no question. I think these drugs and the new ones coming along are going to make it such that everybody is going to be able to lose a significant amount of weight. Our challenge now is helping people keep it off.

Tim Garvey:

Yeah. The other reason people stop these, of course, is the side effects, mostly gastrointestinal nausea, vomiting, constipation. If we're going to talk about a maintenance medicine, what would that look like? What would the profile be? It'd be a medicine that's very well tolerated, perhaps oral. Some people prefer oral over injectable medications that maintains the patients have a certain amount of appetite and can maintain good nutrition and is safe with respect to cardiovascular outcomes, but also muscle mass and muscle function and bone mass. I think loss of bone with this degree of weight loss is an underappreciated problem. You know, you lose 20% of your body weight, you lose about 2% to 3% of your bone mass. And on these DEXA scans that we measure bone mass, we have a Z-score that drops that Z-score down into a range that can increase your fracture risk. So I think a long-term complication, perhaps I'm just speculating here that we need to pay attention to is future falls and fractures with the less muscle mass and the less bone mass that people will have after weight loss like this. So we need medicines that pay attention to those things. And actually, in one study, this SELECT study, which was a longer-term four-year study for cardiovascular outcomes with semaglutide, we did see more falls in patients randomized to semaglutide. So I really think that this is something we have to pay attention to in the future.

As we get more data and learn how to maintain the weight loss in people, like I say, we need data. We're doing the best we can, but it doesn't look like these powerful GLP-1 receptor agonists is going to be the ticket for long-term care.

Jim Hill:

Are you concerned, Tim, there's a lot of, in the media, concerned about loss of muscle mass, that the drugs might produce a greater decline in muscle mass than would be expected? I think it's far from clear that that's the case, but are you seeing concerns and maybe some populations that might be particularly susceptible.

Tim Garvey:

Yeah, I don't know of any data that says you're losing an abnormal amount of muscle mass. I think that by and large, the muscle that's lost is concomitant with the overall weight loss. If you lost that amount of weight through any means, you'd still be losing about the same amount of muscle. It hasn't been precisely delineated, though, yet, I think, in a robust way. But the data we have would suggest that that's true. Now, what people haven't measured as well is the function of muscle. I mean, your muscle is going to be weaker if you have less volume of muscle. I mean, everybody knows that. But patients are also carrying around less weight. So this muscle loss, by and large, hasn't proven to be a clinical problem. I mean, with bariatric surgery, patients lose a lot of weight. That's been around for a while. Muscle weakness has not been a big issue in these trials with these weight loss medicines, second-generation medicines, we always assess physical activity, mostly by questionnaire, and physical activity improves, quality of life improves. But that's not to say that there's subpopulations, like you said, Jim, perhaps elderly folks and definitely people with identifiable sarcopenia. We do have to pay attention to this.

Jim Hill:

I worry about people like us, Tim, old people that, and, you know, I remember back in the Look Ahead trial when the elderly or the older people lost weight and regained it, they actually regained more fat and less muscle. And so that's the group that I hope we get more research to understand.

Tim Garvey:

Absolutely. And also the popular appeal. I mean, if I told you guys, "All right, I'm going to give you a medicine, you're going to lose 20% of your body weight. You're going to be looking pretty good. We can do that with you losing the muscle mass, or we can preserve your muscles." You're going to say, "Oh, well, I want to keep my muscles." So that's going to have popular allure. As companies try to develop medicines that do preserve muscle mass. But, you know, we have to prove that it has health benefits that accrue to that.

Tim Garvey:

And it's value added in terms of health benefits. So we'll see how that plays out.

Holly Wyatt:

So I'm going to switch just a little bit. But we've had some listener questions about this. What do we still not understand maybe about stopping these medications? Is there something that could be negative by stopping it? And things like, is there a hidden withdrawal effect or does it make it harder the next time? Is there something that when you take away the medication, your physiology does something that could be harmful or make things difficult?

Tim Garvey:

Holly, I haven't seen that. Maybe you're thinking along lines that I'm not. Their appetite returns. And like I say, people regain weight, and patients that have this fatigue syndrome start feeling better.

Holly Wyatt:

Yeah. But what about their appetite? I've had a few people, and this is anecdotal. This isn't necessarily from a drug study or a pharmaceutical study. I don't know that they've studied this, come off the medication, and they're like, my appetite came back game busters. Like I was searching for anything and everything, and And it was just a constant (and this is anecdotal) like it was bigger, my appetite was bigger than it ever was.

Tim Garvey:

Yes. Some patients do say that's the case. I think they're just not used to having an appetite. So when it comes back, it's kind of news. But that could be true. These studies do always follow patients after the discontinuation of the medicine for a number of weeks, six, eight weeks, maybe 12 weeks to see how patients do. The weight regain starts almost immediately, then kind of comes up. It seems to kind of start leveling off before it gets back up to the previous baseline. And I just wonder if we followed patients longer, where would we be? Would it really always go back to baseline eventually? Or might it be just a little bit below where they started from? I don't know that yet, but they do regain weight.

Jim Hill:

Interesting.

Tim Garvey:

But sometimes they're happy to have that appetite back.

Jim Hill:

Tim, you've been involved in a lot of clinical trials, but as you know, there's a difference between clinical trials in real life. And most people out there aren't going to be able to come to an expert like you. They're going to go to their family practice doc, etc. And I know you're spending a lot of effort trying to educate these docs about the meds. What are you seeing? I know in the past, we've had some problems with obesity meds. Are you seeing the primary care guys and so forth being more acceptable of these?

Tim Garvey:

Well, yeah, they've got to be because the patients are coming to them and demanding these medicines. I mean, the word is out. There's commercials on TV with people running through the meadows and throwing Frisbees. Patients are flocking in. My primary care doctor says, "Hey, they want me to be an obesity doctor. I mean, everybody wants obesity medicine." So, they're learning how to use these medicines. It's not a slam dunk. I mean, you've got to spend some time and get some experience. But yeah, this primary care is where the treatment should belongs here because this is a very common disease, as you know. You're taking overweight and obesity, that's like half of our country or more, which is another problem. Are we going to put half of society on these powerful drugs? I mean, we've got to work on environment.

Holly Wyatt:

Well, let's move that into cost. So just the cost, and that's a lot of times why someone will stop the drug is their insurance will not pay for it. They are expensive at this point. So cost of putting half the population and who would pay for that? Do you think the cost is going to change moving forward?

Tim Garvey:

The costs have got to come down. In the SELECT study, it was cardioprotective. This prevented heart attacks and strokes in people that already had cardiovascular disease. So we call that secondary prevention. It prevents you from having another event. So it's life-saving. So these medicines can be life-saving if given to the right patients. And are we going to deny patients life-saving medicines because they don't have access, because they can't afford it? We've taken the Hippocratic Oath, and that's just not consistent with the Hippocratic Oath. I think we can't deny patients life-saving medicines. So the costs have got to come down. It's not tenable to me to have patients lacking access to these medicines.

Jim Hill:

The problem is, Tim, the insurance companies don't take the Hippocratic Oath, and they're really looking at the bottom line. And what I worry is now you're seeing half the people stop taking them. The insurance companies are going to say, well, why would we cover it when they're going to regain all this? So I worry that that's going to be used negatively to deny coverage of some of these things.

Tim Garvey:

But you know, what I see happening, you know, I was part of some guidelines from the American Association of Clinical Endocrinology in 2016. And I think we were the first to most explicitly recommend a complication-centric approach to care. In other words, we're using these medicines not to lose X amount of weight. The primary objective is to lose the amount of weight you need to improve quality of life and treat the complications. 50% of America has this disease. That's a rational way to decide when you prefer to use medications. If you use these aggressive treatments and those who can most benefit from the drug, Your risk-benefit ratio for the intervention improves, and the cost-effectiveness does, too. So I see more and more, like CMS has now approved semaglutide for patients that have obesity and have heart disease. And CMS now has a list of what they have accepted as obesity-related diseases. And it's the things we all think about, you know, sleep apnea and metabolic syndrome and osteoarthritis. arthritis. And so there's codes now that they have in CMS for patients that have obesity with these complications.

And the drug companies now are seeing if they improve risk of heart disease, if they improve sleep apnea, if they improve fatty liver disease, and prevent diabetes and treat diabetes. So we're gradually orienting to using these medicines and people who have these complications preferentially because those are the people whose health is really going to benefit from them. If you treat patients based on some kind of staging of disease severity, Again, when you bring more aggressive treatments to those who are sicker, really, that seems rational to me, and at least a way to go forward with this.

Holly Wyatt:

Yeah, and I understand that, and we talk a lot about risk-benefit, and so the ones that get a greater benefit, you take more risk, and it makes sense if you have limited resources who you're going to treat. But I'll say, when I talk to my patients, here's what they say back to me. Okay, Holly, so I should go out and get type 2 diabetes, so my medication will be covered. I should go out and gain 10 more pounds, or I should go out and eat in a way that my cholesterol will go up, so now I can get the drug, I can be treated. I understand that too. It doesn't sometimes make sense. It's like, wow, you want to wait till I'm that sick before I can use a treatment for my disease.

Tim Garvey:

You're right on target there. Of course, you could use less expensive first-generation medicines there in some of those instances as well. Those are still good medicines, and we need all these arrows in our quiver. Like you said, not everybody responds to every medicine to the degree we want. So we might need to switch to another medicine. So we need all of these medicines available. But I was kind of smiling because these guidelines, like I mentioned, complication-based guidelines and this, you know, staging disease and treating according to how sick the patient may be, you know, that looks good on paper. But like I said, these patients are coming in and talking to their doctors and saying, listen, I have a weight problem and I've really tried to lose weight and I've tried several diets and I want help with this. And you have a contract with that patient to try to help them and improve their quality of life in a safe way. And so, you know, that's where these guidelines, the implementation falls down a little bit because, you know, people are people and we want to help who's ever in front of us. And this is what patients want.

Holly Wyatt:

Well, do we value prevention? Preventing type 2 diabetes, is that less important than treating type 2 diabetes? I mean, that's the thoughts there.

Tim Garvey:

Well, in the middle of this right now with updating the ACE guidelines and the Lancet Commission on Obesity, some of these big, you know, all these kind of head honchos and experts get together and kind of drink a lot of coffee and kind of figure out how we should go forward. And they've recognized that there are patients that have obesity that don't have complications. And ACE would call that stage one. And the Lancet Commission calls that preclinical obesity. It's excess adiposity, but it hasn't led to complications or related diseases at that point. So, what do you do? That doesn't mean that these patients shouldn't be treated because they're at high risk of progressive disease and high risk of getting complications. And you're right. Even the second-generation medicines, you know, if patients who are at high risk should get these medicines in a preventive intent of treatment.

Jim Hill:

Tim, I want to go back a little bit too. I think it's terribly important that we educate the primary care folks. And again, in the data about dropouts, if you remember, you were less likely to discontinue the meds if you were prescribed by an obesity expert. So there's something happening. And I suspect it's the obesity experts better being able to explain the need for long-term care and everything. And so I think there's some opportunity to educate the primary care guys. And the other thing I would love to see is when people are put on these drugs for whoever prescribing it to start them thinking about your long-term strategy. Think beyond weight loss. What are you thinking? What are your options on keeping it off?

Tim Garvey:

Yeah. I don't think we do that as well as we should. And, you know, I think that maybe what the obesity medicine docs have that primary care doesn't have yet is, this is an art. Treating these patients is, there's a lot of art to this. And you need to treat these patients empathetically, give them support, encourage them. They're used to being shamed for their obesity, not only in society and social media, but in healthcare systems. And primary care, maybe they just don't get this. And sometimes they don't have time to really interact with the patient on these terms, but then they should have staff trained to do this. But at any rate, I think it's the art of telling people what the positives and negatives, what the side effects are going to be. We're here to work with you. We've established what our goals are. We're going to be there for you. This is not your fault that you have this disease. We understand you need help, and this is how it's impacting your health.

This sort of thing, empathy and information and support. If people start treating obesity for the first time, they might not have this in their of how to do that optimally.

Jim Hill:

You know, Tim, in our department, we train a lot of registered dietitians. And I think registered dietitians can play a role in helping these patients with weight loss meds, because as you said before, there are nutritional deficiencies. What do you eat? How do you manage your appetite? So I think there's a role for some of these other health professionals to play a role in helping people actually, you know, learn to live a lifestyle with the medications.

Tim Garvey:

Absolutely. We have evidence that it's a team approach. We need a team to treat these patients. And that's maybe another reason why obesity medicine doctors that have these resources built into their practice do better than primary care. These docs are treating a wide variety of diseases. And yes, you're right. Lifestyle coaches, dietitians, exercise trainers, and there's always a psychological overlay to this disease. And if you don't deal with some of these factors up front, like depression, anxiety, internalized weight bias, and binge eating, your therapy is just not going to be as successful. So you have to pay attention to those things, do referrals when you need to. Also, we need to take into account social determinants of health more.

If we have a treatment plan where patients can't walk because it's not safe at night and they can't get unprocessed foods or they can't afford the medicine that you're prescribing, their literacy is such that they don't understand the way you're providing information to them. If you don't take all of these factors, social determinants of health into account and individualizing your treatment plan, again, you're not going to be successful. So, you have to be a good doctor to be an obesity doctor.

Jim Hill:

It is. Holly, I'm glad you mentioned exercise. I want to put in a plug here because the meds don't affect exercise. I think a lot of people said, well, when people lose weight, they're going to start exercising. I'm not sure that's the case. Maybe some of them are, but exercise can improve health. Weight loss clearly improves health. Exercise fitness can add an extra dimension to that. And so I think it's an opportunity when people do lose weight, they may be more willing to start education or physical activity. But I think we need to help them do that.

Tim Garvey:

Yeah, I think this speaks to the health-promoting aspects of a lifestyle intervention, which all patients should have. You know, with these first-generation medicines, it was more critical for weight loss, to achieve weight loss. With these second generations, they're so powerful.

Jim Hill:

You don't need them for weight loss.

Tim Garvey:

But you do need them for health, okay?

Jim Hill:

Yes, that's it.

Tim Garvey:

Yeah, and there's cardiovascular risk factors that are improved. There's quality of life. It can improve some of the psychological disorders that I mentioned, and patients just feel better. And same with the dietary intervention component. So, yeah, they still need those. And it promotes health, even though it might not add a lot to the weight loss on top of these second-generation medications.

Holly Wyatt:

I want us to have a little bit of time to talk about the future because we get lots of questions about what's coming. Kind of what I've heard thus far is the expectations of the patients need to think beyond weight loss. They need to be thinking long-term. That's one of the things that it can help. I think that doctors need to realize it's not just simply prescribing medication. It's way bigger than that. I think that would help. And then like Jim said, this health-related piece of it. That's more than just weight. And all three of those things, I think, can help improve the long-term success and maybe keep the weight off for longer periods of time. But the future, do we have new drugs in the pipeline? I know you are on the cutting edge. Some things you probably can't tell us, but new things coming, a pill version that works for the GLP-1s, could that be a possibility? Would that change things? Look into your crystal ball and tell us what's coming, Tim?

Tim Garvey:

Well, it's amazing what's in the pipeline. I mean, these, not just big pharma companies, but very small biotech companies, everybody's kind of entered, they call it enter this space, this area of drug development. Because I guess, I don't want to be crass about this, but they see they can make money with this.

Jim Hill:

Yeah, lots of money.

Tim Garvey:

So that kind of brings the development into the forefront. So there's a lot of development going on. I think it's actually very exciting. There's more powerful weight loss medications being in trials right now. And these companies, unfortunately, they get this mindset where they have to kind of one-up the next guy and have even more weight loss than the other drug. And some of their investors are kind of driving that. I think, we have powerful medicines and patients lose too much weight often. And we just need medicines that are safe and tolerated that are also effective. And so I think, eventually, we've got to come around to that, and to me, that means moving beyond GLP-1 receptor agonists. I think we need to think out of the side of the box and develop other kind of tools with other targets. But yes, there are oral, a couple of companies, three companies, in fact, are very active in developing oral small molecules that you can just take. You don't have to take them with any kind of food. You don't have to worry about meals. You just take them once a day, and they activate this GLP-1 receptor just like the injectables do. They seem to be nearly as effective, if not just as effective as the injectables, but they still have the side effects. You don't get around the nausea and vomiting, and you still have to start at a smaller dose and escalate it to kind of mitigate those symptoms. I think that's good, too, to have that tool in your quiver because some patients prefer oral rather than a weekly injectable, and that's fine. There's also other kind of nutrient-regulated hormones. These, GLP-1 and GIP, these are all hormones that increase after a meal and suppress your appetite. So these drugs try to mimic these natural hormones that we have. So there's drugs addressing some of these other hormones. Amylin is one. PYY is another.

Tim Garvey:

And I think even these cannabinoid receptor blockers are coming back that, well, we've had an experience a while back with those. It didn't work out so well.

Holly Wyatt:

Right, right.

Tim Garvey:

They claim there's better versions afoot here.

Holly Wyatt:

So we have to let our listeners know those are the anti-marijuana drugs, right?

Tim Garvey:

Right. Yeah.

Holly Wyatt:

Yeah. So they have an idea what that was. We had a drug like that and it didn't pan out, but you're saying they're really looking at it.

Jim Hill:

I think the future is very exciting. And I do think it's not going to be long before there's a medication that's going to work for just about everybody to get the weight off. All right, Holly, we've handled the listener questions. You want to jump to the vulnerability questions?

Holly Wyatt:

Yes. Let me pick a good one for Tim. So, Tim, this is where we ask a question that you have to get a little bit vulnerable, maybe say something a little bit about yourself. Let's see. Have you ever been surprised by how patients respond to these medications, either successes or struggles? When have you been wrong or surprised or said, I didn't think that was going to go that way, but it did?

Tim Garvey:

Yeah. Well, I'll tell you a good direction and a bad direction. This one patient comes to mind. This was about a 50-year-old male. BMI was about 40. This guy was just, he was depressed. He couldn't walk very well. His diabetes was way out of control despite being on like three or four medicines, including insulin. Still wasn't controlling. He had sleep apnea. He just was a wreck. He just was not enjoying life at all. And he came into one of our trials and lost I don't know, 20% of his body weight, something like that. And he was just a new person. He was bright, articulate, happy, sleeping well, had so much more energy, enjoying life. His diabetes was under control. His blood pressure was under control. It was life transforming. When a doctor sees this, I mean, it's so rewarding, actually. And it just kind of warmed my heart to see a patient respond like that and to have a tool that could help somebody to that degree.

Holly Wyatt:

Yeah, really a holistic response. Everything changed.

Tim Garvey:

His health, outlook, you know, there's outlook on life, there's energy, etc. So it was a holistic response. To the negative, some patients can't tolerate these medicines, and they can have a lot of vomiting and can only tolerate very low doses. But we picked up a side effect that was a little unusual that people hadn't anticipated. And that's in a minority of patients. Sometimes these drugs cause the skin to be very sensitive. The skin feels abnormal. We call it dysesthesia is the medical name for it. But in some patients, it can be painful. And we had a patient that went to Italy on a vacation and we get this call and his skin was so painful, he couldn't put his shirt on. And we took them off the medicine and it got better. But it took days to get better.

Tim Garvey:

And I looked it up. There's these GLP-1 receptors in peripheral nerves. I don't know what the mechanism is, but now this is being recognized more widely. And the clinical trials are building in questions where you ask the patient, how's their skin doing? But maybe 7% of patients on the higher doses of these medicines can develop these kind of, usually pretty mild, it may be unrecorded, so patients just kind of feel their skin's a little different and they don't say anything about it. So, but that's something I never anticipated.

Holly Wyatt:

Which just shows you why we need clinical trials that are really out there looking in a broad way for side effects, because we wouldn't, you wouldn't have expected that. That didn't make sense in terms of the drug, but it was there. So that just shows the importance of doing these clinical trials the right way.

Tim Garvey:

Right.

Jim Hill:

So Tim, before we ended here, what's your advice for our listeners? These are people that may be managing their weight. They may be thinking about the meds or thinking about weight loss. They may have tried every diet under the sun before and lost weight and regained it. What's your advice to them?

Tim Garvey:

Well, first they have to understand that they have a disease and this is not their fault. The fact that they've had so hard a time kind of trying to manage this over their lifetime. They've suffered for this. They've been stigmatized and they've internalized this bias, internalized weight bias, and they just have to understand this is not their fault. And they have to understand there's help that they can get and they deserve help. That's not to say we have, these aren't magic pills, okay? We have tools. No medicine's perfect, but if we work with the patient individualized care, if they stay with us over a longer period of time, I think we can help them out. We have the tools to do it, and they don't have to suffer with this if that's where they're at.

Jim Hill:

Fantastic. Well, thanks. And I would say the takeaway, Tim, here, and see if you agree, is these new medications are powerful tools. And you and I have been around long enough that we struggled with fairly weak tools. Now we have a major powerful tool. And I think we're now trying to figure out the best way to use that tool. But it's here to stay. And it really is a positive game changer for our field.

Tim Garvey:

You know, I gave a talk not too long ago where I equated the current era of obesity medicine development as a landmark in the history of medicine. And I put it on the level of the discovery of insulin, the discovery of penicillin, and the polio vaccine, which are all landmarks in the history of medicine. But I think when you think about how common this disease is, how much suffering it exerts, and the social costs that attend to this disease, and the degree to which these medicines can transform patients' lives and transform our approach to care, I think it deserves that kind of perspective. We're living in the middle of a landmark in the history of medicine.

Jim Hill:

Wow, fantastic.

Holly Wyatt:

Can't wait to see. I can't wait to have said we were part of this, right? We are here for this.

Tim Garvey:

Yeah.

Jim Hill:

Tim, thank you for your time and thanks for all you do. You really are a major leading force in moving the treatment of obesity forward. So thanks for all you do. Thanks for all of our listeners. Send in questions. We love to get your questions and we'll talk to you next time on Weight Loss And.

Holly Wyatt:

Bye, everybody.

Jim Hill:

And that's a wrap for today's episode of Weight Loss And. We hope you enjoy diving into the world of weight loss with us.

Holly Wyatt:

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Jim Hill:

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Holly Wyatt:

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