What Happens When You Stop Taking GLP-1s?

John Horton:

Hey there and welcome to another Health Essentials Podcast. I'm John Horton, your host. GLP-1 medications like Ozempic have changed the conversation around weight loss and weight management. But while GLP-1s are meant to be used over the long haul, many people come off of them within the first year. So what happens when you stop and what does it mean for your health? We're going to talk through that today with endocrinologist and obesity medicine specialist Peminda Cabandugama, who is also a Fellow of the Obesity Society. Dr. C is one of the many experts at Cleveland Clinic who join us weekly to help us better understand medicine and how it works with our bodies. Now let's find out what you can expect when you end GLP-1 treatment and why it's so important to plan out those steps. Welcome back to the podcast, Dr. C. We always enjoy getting some time with you to pick your brain.

Dr. Peminda Cabandugama:

Thanks for having me, John. I'm always looking forward to these things.

John Horton:

Well, we love having you in. And as we've talked about when you've been on before, obesity is a chronic condition, which is why GLP-1s like Ozempic are kind of designed for long-term use to be a solution. But the reality is that most people who start these weight loss medications actually stop taking them within a year. What typically happens when folks leave their treatment plan?

Dr. Peminda Cabandugama:

Yeah, I think that's a great question. A lot of people have a misconception and even there are some stats that kind of point to this, that a lot of people get off GLP-1 medications for side effects. But if you actually look at the numbers, the main issue with the GLP-1s has always been access, so getting access to these medications is one of the main reasons people get off. So the question you asked is what happens when they get off? And the majority of the studies do show that a lot of patients tend to gain weight back. Usually we've been quoted numbers, up to about 60% of patients can gain their weight back when they get off these medications. And with that comes all the obviously chronic conditions that go with weight.

John Horton:

Right. And I saw that's where you get blood sugar spikes, just your appetite jumps up. These are all kind of byproducts of stopping the medications.

Dr. Peminda Cabandugama:

Yeah, that's correct. So obesity or weight management, it's a chronic condition just like everything else, like Type 2 diabetes, high blood pressure, high cholesterol, sleep apnea. Because there is such a close interrelationship between obesity and all these other chronic conditions, yeah, we see a bump up as the weight comes back on.

John Horton:

Well, let's dig a little deeper into the effects that we just kind of talked about, starting with appetite return. Why do people feel just so much hungrier once they stop taking GLP-1s?

Dr. Peminda Cabandugama:

Right. To understand that, you have to understand how the GLP-1 medications work. The reason they call these medications the second generation or the next generation weight loss medications or the game changers as they're called, is because these medications have that two-pronged effect that I've mentioned even in our previous podcast. One of the things it does is it slows down food in your stomach or slows down gastric emptying, and then it also works in our dopamine centers in our brain to actually help cut down cravings.

So as opposed to previous medications or medical options for weight loss where there's just a one-pronged approach, these medications work in these two different ways to not only effectively drop a significant amount of weight, but when you withdraw these medications, both those kind of issues that lead to weight gain come back. And so that's the reason why we have that significant weight gain.

John Horton:

Yeah. I mean, that totally makes sense because it sounds like when you take the medications, just slowing that digestive process down, you feel full longer. So you're not even thinking about eating because you're feeling pretty good.

Dr. Peminda Cabandugama:

That's correct. There's two main, for now, discovered hormones or peptides in our body that control eating. There are a few more, obviously, in place also, but the two main ones is the Ghrelin hormone, which, we colloquially call it the stomach growling hormone. That's the one that tells you that you're hungry.

John Horton:

I hear that one a lot.

Dr. Peminda Cabandugama:

Yep, that's the one that people usually feel the effects of a lot more. And then there's the other one which is the Leptin hormone, which is our satiety hormone. That's the hormone that gets released between meals. So that says that, "Hey, I've had a meal, I'm feeling satiated." That's a satiety hormone that says, "Okay, I don't need to eat until lunch." So the combination of those two hormones and the actions of everything else we do for weight management is kind of what plays a role in our hunger during a meal as well as between meals.

John Horton:

Yeah. Well, and then it totally makes sense that if you start craving food a little bit more, you might start seeing the numbers creep back up on the scale. You said, what is it, 60% of people start regaining weight once they stop taking GLP-1s?

Dr. Peminda Cabandugama:

That is correct. There's quite a few studies that show that, that with the current generation of medications, up to two thirds of people, so 60% to 66% of people do gain the weight back. However, for those of us who look in depth into those studies, we do notice that those are the people who focused on only the GLP-1 medication to help them with their weight management journey without the diet and exercise. I just want to make it very clear to everyone listening that all these studies and what we recommend, especially at the Cleveland Clinic with our multimodal approach, is that all these GLP-1 medications or the combos work with a reduced calorie diet as well as regular exercise, which translates to about 150 minutes a week of exercise.

So just like how obesity and weight management is a chronic multifactorial disease, the treatment of it needs to be chronic and multifactorial. That's the reason we've seen that. Now, there are some newer studies coming out that shows that some of these medications may not even need diet and exercise, the medication itself will do a lot more heavy lifting, but those are still trickling out. But the current studies do show that at least two thirds of people will gain the weight back once they get off the medication.

John Horton:

Yeah. Dr. C, that's such a great point because you don't want to look at these as they're just magic pills and they're just going to get the weight off you. They give you that little extra nudge you might need, along with, like I said, eating a little bit of a healthier diet, exercising a little more to help push along that weight loss process and just make everything healthier. When you stop taking the medications and you do regain the weight back, are we talking that you kind of go back to where you started? Could you even go higher because all of a sudden now you're craving it so much more and maybe you dig in a little deeper into that buffet?

Dr. Peminda Cabandugama:

Yeah, that's another great question. Current studies do show, and we've seen this even in previous weight loss medications and other modalities like bariatric surgery, weight loss surgery, where people who focus just on the one intervention, whether it's surgery or medication, they not only tend to gain the weight, but they also tend to overshoot. And what that means is actually gain more weight than what they started out as. I think it again, speaks to the multifactorial nature of what weight and eating means, because everything that's happening even now, even though there's such a large boom in weight management, we are still kind of at the tip of the iceberg. There's so many other brain signaling pathways and hormones, peptides like we talked about within our body, and also just the day-to-day stressors, the socioeconomic stressors that we have that actually lead to eating patterns.

When I talk to my patients and they talk about, "Oh, maybe in the '50s people didn't gain as much weight," and then I would talk to them, "Okay, maybe in the '50s, both parents didn't have to work. Maybe one parent would stay at home and make home-cooked meals, which usually tend to be healthier than eating from out." We don't deal with the daily stressors that we have with increased screen time, not only with us as adults, but with kids. Again, it speaks to the fact that weight has these multifactorial etiologies and these medications, like you very correctly said, they boost what we always do. And I make it a point to tell my patients that all the time when they come to see me, that whatever you are already doing with your diet and exercise gets boosted by these medications.

And that's why I think I always make it a point to also do my labs and show my patients how their cholesterol gets better, which means they're also, without realizing it, eating better. But also things like the HDL, the good cholesterol goes up, which I tell them, "You might not have realized it, but you're actually moving more now." And then they're like, "You know what? Yeah, I started now, walking more, walking my dog more and all of that." So it speaks to the fact that obesity and weight management treatment modality, especially with the GLP-1s, have come a long way from what we though from back in the day where, hey, this is like a magic pill to fix something. It's a multifactorial disease, chronic disease treated in a multifactorial way and in a chronic way.

John Horton:

Now, one of the main reasons why people end up starting GLP-1s is to try to avoid getting Type 2 diabetes. And that's so tied to weight management and obesity and things like that. So it kind of makes sense that if you stop taking the medications, that your risk for blood sugar issues and your diabetes risk might increase. Do you see that happen too, when people just stop taking it?

Dr. Peminda Cabandugama:

Yeah, so that is a very important point. I think you and I, we talked a little bit even in preparation for this podcast. And like I mentioned, the first one of the popular GLP-1s is Ozempic, which is known as, obviously semaglutide, the brand name is Ozempic. Next year, 2027 is the 10-year anniversary of its FDA approval, and it was first approved for diabetes. So these are diabetic medications where we found the side effect was obviously weight loss and then became popular for that. Yeah, I mean, before we started calling these medications weight loss medications, when it was first a diabetic medication, it's like any other diabetic medication. If you get off your insulin, your sugars are going to come up. If you get off your metformin, your sugars can come up.

It's the same concept here, but obviously the next step is there is that close interrelationship, we know, with increased weight gain and increased insulin resistance. So if you get off the medication and the weight comes up, it just stands to reason that your blood sugars are going to come up and your insulin resistance gets worsened. And just to tie to that point, people ask me, "Hey, Dr. C, when I go on vacation, if it's the holidays, can I not take this medication?" And I tell them, I use this point to say, "Hey, if you though about this just from a diabetes point of view, would you just stop the medication? You wouldn't."

John Horton:

You wouldn't stop your insulin when you're on vacation or something like that.

Dr. Peminda Cabandugama:

Correct, that is exactly right. So we're trying to get people to get into the mentality of understanding that this is not just a aesthetic problem where it's how you look or anything like that, but it's a chronic disease that correlates with a bunch of other chronic diseases. So you need to make sure you're taking it to help your chronic disease that is obesity, and then that obviously will help with all the other chronic diseases that it relates to.

John Horton:

Yeah. That answer just to me, really drives home the point. And one of the difficulties when we talk about weight loss is we get so fixated on pounds and that number you see on the scale. And in reality, weight management isn't just about that, it's about making your body healthier. And most of the time when you lose weight, you also, like you said, you address factors like blood sugar issues, you address cholesterol, blood pressure. So it's not just looking better in your swimsuit, it's making your body just healthier for day-to-day life.

Dr. Peminda Cabandugama:

That is a very, very important point, because I tell my patients when I talk to them, the scale cannot tell the difference between fat, muscle and bone. Weight is made up of all of those. And I mean, I could talk for hours about what that means, but the basic gist of it is that even other than the fact that you mentioned with the metabolic conditions that come with weight like diabetes and heart disease, the most important thing we're trying to do is improve peoples' quality of life and obviously, that ties into longevity. But living longer and doing better also has to be with a better quality of life.

So if you take even the mechanical consequences of weight, my patients who do the best and who just find that their quality of life improved with these GLP-1s, come back and tell me, "You know what, Dr. C? I'm able to climb up and down stairs a lot better. I'm able to get up and down with my grandkids better." I mean, it's making sure that, like I said, people live longer with a better quality of life, and that doesn't always translate to the weight on the scale. We do have other metrics that we look at like body composition for muscle mass and all of that. But the main thing is along with all the metabolic conditions improving, it should be very clear that this is not an aesthetic thing, but it's about improving the quality of life of that person.

John Horton:

All right, so taking everything we just talked about, all these issues, which is why people start taking GLP-1s, this quality of life and just being healthier and all of that, is it a good idea to just stop taking GLP-1s? It seems like the intent is for this to be kind of a long-term medication to use to help your health. Should you just kaput, like you're not taking it anymore?

Dr. Peminda Cabandugama:

Yeah, so that answer to that question is tied to the question you asked me before. If we are saying, "I'm stopping the medication because I can't afford it," I mean, yes, that is a barrier that unfortunately, hopefully will get resolved by everyone that has the power to change that, to improve access. But if you're getting off the medication because you think, "You know what, I just got to my goal weight now," you have to realize that you are then mistaking weight as an aesthetic problem and not something as a quality of life. Because weight is so interrelated to all other chronic conditions, and we know this and we're getting even more and more information on this.

There is a caveat to all of that, which is related to the last question you asked me, which is about the scale. Weight is a bell-shaped curve, so it's a bell-shaped curve like this. What that means is being overweight and obese is not good, but being underweight is not good also. So when your body mass index goes below 20 and 19 and 18, that means you are not losing the fat tissue, you're losing muscle and bone. And I tell this to my patients a lot. It gets a big laugh at all the lectures that I give, which is, "You will look like a model and walk with crutches, that's not what you want." So what you want to do is achieve-

John Horton:

I like that saying, that's fabulous.

Dr. Peminda Cabandugama:

So again, it has to do with your goals, it has to do with improving your quality of life. With my younger females, it has to do with, and even males, but mainly with my younger females, since the periods are so tied to weight, it means improving fertility in the long run if they want to get pregnant. I mean, these are all things that we as human beings associate with quality of life and having a good quality of life.

So these are things that we want people to learn when they deal with weight. And this is another reason why we always tell our patients, even if I meet somebody on the street and they ask me about it, I say, "Make sure you meet with a board certified weight loss physician, somebody who can educate you on the good and the bad things about weight management and who's able to guide you in this process in a safe manner."

John Horton:

Well, and let's talk about the guiding to the process when you just decide to stop taking GLP-1s. I know you said there's a lot of reasons why people do that, they make that decision, with one of the biggest being cost and that sort of thing. But when you then start that process and you're like, "All right, I'm off of these," is there a good way to do it? I mean, is it just you do it cold turkey? I've read things where people might try micro-dosing to try to stretch it out. What's the safe way to go about this?

Dr. Peminda Cabandugama:

Yeah, so that's another great question, and I think that is something that a lot of the obesity societies are currently working on to figure out and also to guide people on. And as you know, I sit on a few of the national boards, so I'm part of that. We don't have a good answer yet. You can stop it cold turkey, yes. There's no kind of taper process or anything like that. Micro-dosing is kind of a phenomenon that I think a lot of people started using to get over that hurdle of access. So if you can't afford it, they're like, "Can I stretch it out?" There are studies coming out on that. It is kind of off-label, so I'll just talk a little bit about it without going in depth, because the Cleveland Clinic's policies is we try to avoid off-label if we can.

The problem that we have with micro-dosing is the current iteration of GLP-1s, which is tirzepatide and semaglutide, the actual pharmacokinetics of these medications is actually five days, not seven. So technically, they're already kind of stretched. They're at seven days because we take them once a week right now. So I don't know if we can talk about the effectiveness of that medication, if it's once every 10 days or once every 14 days. And then the other thing is the devices that inject the medications, they're set up in such a way to be given dispensed like that. So if you're trying to maybe use another needle and draw out medication from a prefilled syringe, then you look at other issues like infection and bleeding and all of that. So there's all these kind of problems that are coming up with it.

But I can tell you in the weight management world, I mean, for those people watching this who have experience in this world already, there are currently quite a few options that are coming out, whether there's a possibility to maybe transition people from the shots to the pills when they're at a lower weight. There is a lot of work being done with a medication that's going to be once a month. So there's a lot of different options that will come out which will answer this question. But in terms of right now, if you were to get off of it, yeah, you can just get off of it completely without really a taper process.

But hopefully a bunch of higher ups in all the different obesity societies, whether it's the Obesity Society, whether it's the Obesity Medicine Association, whether it's Pediatric Obesity, if it's Obesity Canada, I mean, they're all working together actually for the first time, which is fantastic, to hopefully come up with what we are hoping to be called standards of care for weight management. And one of these, this question that you just asked will be one of the cardinal questions they'll look at.

John Horton:

Yeah. Well, let me ask you this, though. If somebody, you're on GLP-1s and you're on them for a year or so and you get your weight under control, you get your eating under control, you change your diet, you start an exercise program, you do all the things that you should do to maintain that healthy weight and healthy lifestyle. Do you see some people have success then, once they shed the extra pounds where they're able then to just maintain that weight if they follow that healthy lifestyle that we've been talking about?

Dr. Peminda Cabandugama:

Yes, 100%. And I tell those people, they graduated from my clinic, but again, I'm very careful when, I mean, there really are just a few people who do that. And that is because with the GLP-1 medications, we know that these medications obviously became more popular when celebrities used it for weight loss and all of that. But like I said, these medications have been around for a long time right now. And contrary to popular opinion, these medications are not just FDA approved for weight loss or even for just diabetes. These medications are currently approved for fatty liver, for sleep apnea, for chronic kidney disease, for protecting the heart. Tirzepatide just got that approval for diabetics just last week, for giving cardiovascular protection in diabetics, Type 2 diabetics.

So the patients who even get to their goal weight, I still tell them, "We should try to keep you on a maintenance dose of the medication," but at that point it's not for weight. It's actually for the other chronic condition. We want to make sure that the diabetes doesn't come back, we want to make sure we keep the heart protected. Because if you're a diabetic, as an endocrinologist, one of the things we always try to do is protect the heart in diabetics because we know that Type 2 diabetes and Type 1 diabetes can lead to neuropathy and cause heart attacks, so we want to keep that heart protected.

I do want to say that that is kind of my process where I keep them on the first therapeutic dose of the medication when they get to their goal weight, whatever that is for different people, for the other conditions like diabetes and fatty liver and all of that. And even that, they're trying to find out, all the powers that be are trying to find out what we want to do in our standards of care with those patients, how we not only taper somebody off a medication, but how we do maintenance dosing for people who get to their goal weight, usually for the other chronic conditions that go along with weight.

John Horton:

Yeah. I mean, does dosing just become an issue then? When somebody maybe hits their target weight, they've established this healthy lifestyle, that maybe you can drop the dosing down and they can ride that out and use it? Just like you said, there's a little help, but they're not relying on it solely.

Dr. Peminda Cabandugama:

Yeah, so that's exactly what works with my patients. When they get to their goal, I'll put them on the first therapeutic dose, the doses that have been studied for diabetes and heart disease and cholesterol and fatty liver. And then if their weight does go up above certain criteria, we have BMI or body mass index criteria that we use currently. Body mass index might not be the best measure, but that's what we use right now for guidelines. And if their weight goes up, then we can go up on the dose. But if their weight is below that criteria, which is a body mass index of less than 27, but they still have the other chronic conditions like diabetes, high blood pressure, or they have a history of that, then we cut them down to the first therapeutic dose to manage them.

And then if the weight goes up, we will increase the dose. And this is another point where I really used to strengthen it in my patient by really talking to them, to explain that weight is a chronic disease. So if the weight comes back, it doesn't mean you're a failure in any way. If your diabetes comes back, nobody says that you're a failure, they just increase the medication. It's the same thing with the weight, and it's very important to make that distinction so people just don't focus on the aesthetics of weight and actually focus on what it means to have a chronic condition like weight.

John Horton:

Now, if somebody stops taking GLP-1s and that weight does creep back up, the health issues start coming back, maybe the diabetes markers go up, the cholesterol rises, all that, can you go back on GLP-1s? And if so, what's the process to do that?

Dr. Peminda Cabandugama:

That's a really good question. And now that GLP-1s have been around for a little bit longer, we are finding that people who get off the medications don't always do as well the second time around when they get on a GLP-1. And that's why things like access and things like cost is so important, that we try to see that patients who need this medication gets it. This is the concept that is currently being known as metabolic memory. Metabolic memory means your brain seems to have learned from the medication that, "Hey, this person is now taking this to drop my weight and get the sugars down and all of that." So now it makes it a little bit harder to do that because the brain and your body has learned how to counteract this.

So yes, you can get back on it, but the current studies, and they're still working on this, but the concept of metabolic memory is getting strengthened quite a bit, does show that people may not have as robust an effect as they did the first time. And this is why, again, it's very important. I think I've talked to you about this before, John. I'm a big fan of making sure that our patients are successful right from the start. This is why that it's very important that when you go out and get these medical options from people who are not maybe as well-trained or maybe not the best places to get these medications and they're just interested in just pushing a medication on you for a couple of years and then they're like, "Okay, you're on your own." It's important that patients know that you go to people who get trained on this so that they can help to mitigate these problems that happen, as well as, again, I'm very fortunate to work in the Cleveland Clinic.

Right from the start, our patients, all our patients get sent to dieticians and trainers and endocrine psychologists for eating disorders and all these things. All these options that really, like I tell my patients, it's not just about weight loss, but sustained weight loss and improving your quality of life. So again, multifactorial, but also make sure that they're successful in the long run right from the start so that even if you do get off these medications, you have those healthy habits in place right from start from diet and exercise that, if we get off the medication and you need to get back on and the medications are not working as well, we'll still be able to keep you healthy and sustain your weight loss long term.

John Horton:

Yeah. And this kind of gets back to what we had said right at the start, which is that GLP-1s were kind of designed to be a long-term medication, something you could take for the long haul as that kind of assistance tool to help manage your weight. And it sounds like if you start on that process and you're seeing success, staying with it is really the best approach for weight management and your health.

Dr. Peminda Cabandugama:

That is correct. And so again, I hate to beat a dead horse here, but it's that understanding that weight is not an aesthetic thing. Obesity or weight management is not aesthetic. There is multiple, multiple studies that shows that there's a strong correlation with all the other chronic diseases. And so just like any other chronic disease, when you get your sugars under control, you don't get off your diabetic medications.

When your blood pressure's under control, you don't get off your blood pressure medications. It's the same kind of concept here. So if you understand that obesity is a chronic disease that works with all the other chronic diseases, you understand the importance of staying on these medications. Unless it's causing you a problem, so like we talked about if you're losing muscle.

John Horton:

Talk to your healthcare provider and work that out, yeah.

Dr. Peminda Cabandugama:

Correct. And also, it's the same thing with high blood pressure. If you suddenly start having low blood pressure, you don't continue your blood pressure medicine. So if you're suddenly losing too much weight and you're having problems with your bones or anything like that because you're going underweight, you don't stay on the medication. But yeah, the majority of people, we are trying to educate them on the fact that this is a chronic disease that correlates with all other chronic conditions.

John Horton:

Dr. C, just to bring everything home here, I think it's safe to say at this point that GLP-1s are kind of here to stay as a weight and health management tool, but I know folks are still trying to figure out how these medications might fit into Their overall health plan and how they need to look at them moving ahead. What long-term advice would you give someone who's considering using GLP-1s as a weight loss medication?

Dr. Peminda Cabandugama:

Yeah, the main thing is, like you said, have a good conversation with your primary care physician or your prescribing provider, and please seek out somebody who is trained in this when you are thinking of doing a weight loss medication. You will be surprised. It's one of the most common things that I hear in my clinic when people come in to see me, that these medications have so many FDA approvals for heart disease and diabetes and high blood... Sorry, not high blood pressure, but heart disease, chronic kidney disease, fatty liver, sleep apnea. And so the main thing I would tell people is have that conversation with your doctor, see if you're a good candidate for it, for all your chronic conditions, which includes weight. If you realize that, then you will notice that you are going to do a lot better because a lot of these questions that we ask today are like, "Hey, do I need to get off of it? How do I get off of it? Do I need to cut it down?"

All of this, if you think about it as related to your overall chronic conditions and health, then you will realize that these medications, I mean, they really will change your life. Because after a while your doctor will do your labs, show how your sugars get better, cholesterol get better, everything that we go to see a general practitioner for or even an endocrinologist for. And then you will also note at the same time that you're losing weight, which will get you moving around better, hanging out with your family better, living longer with a better quality of life.

John Horton:

Well, Dr. C, I know you mentioned multiple times during this discussion, how there's all this research going on and all these other questions that are coming up and ways to use the medication and that. So I have a feeling we'll have you back on here to talk about GLP-1s again sometime soon. But until then, like I said, thank you so much for coming in and really shedding some light on a topic that I know people are really curious about.

Dr. Peminda Cabandugama:

Always happy to join you, John. I think you and I have a good conversation all the time about these things. It makes me think about stuff too, so that's great. And yeah, thank you so much for having me.

John Horton:

All right. Take care, see you soon.

Dr. Peminda Cabandugama:

See you.

John Horton:

GLP-1s can be a valuable weight loss tool, but like any treatment, it's best to follow a plan. If you're thinking about stopping or restarting the medication, don't try to do it alone. Talk with your healthcare provider to find the healthiest path forward. If you liked what you heard today, please hit the subscribe button and leave a comment to share your thoughts. Until next time, be well.

Speaker 3:

Thank you for listening to Health Essentials, brought to you by Cleveland Clinic and Cleveland Clinic Children's. To make sure you never miss an episode, subscribe wherever you get your podcasts or visit clevelandclinic.org/hepodcast. This podcast is for informational purposes only and is not intended to replace the advice of your own physician.