Answering Your Questions About GLP-1s with Keren Zhou, MD

Podcast Transcript

John Horton:

Hello and welcome to another Health Essentials Podcast. I'm John Horton, your host.

The use of GLP-1 medications for weight loss has exploded, increasing nearly 600% during a recent five-year stretch. By some estimates, 1 out of 8 adults in the United States has used a GLP-1 to shed some pounds. And more and more people keep signing up for the treatment. Of course, folks still appear to have a lot of questions about these medications. And today, we're going to get some answers from endocrinologist Kathy Zhou. Dr. Zhou is one of the many experts at Cleveland Clinic who pop into our weekly podcast to help demystify medicine. So with that, let's take a closer look at GLP-1s and how they work their scale-adjusting magic. Welcome to the podcast, Dr. Zhou. Thanks for stopping by to chat.

Dr. Kathy Zhou:

It's completely my pleasure. Glad to be here.

John Horton:

So I'm pretty sure by this point, we all know a friend or family member who seemed to drop a bunch of pounds and get trim seemingly overnight. And when you ask them how they did it, the answer is often a GLP-1, like Ozempic® or Wegovy®, two brands that come up a lot. What exactly are these miracle medications and how do they change our shape?

Dr. Kathy Zhou:

So it's pretty interesting. So GLP-1 receptor agonists, because they actually work on the receptor that our native GLP works on in the body, are essentially hormone medications — different, of course, than insulin, but nonetheless, a hormone. And they work in a number of different ways. One, they suppress hunger. I mean, a lot of my patients describe it as almost like hunger becomes white noise. People forget to eat, which can become problematic, of course, but it becomes a secondary issue for them. It also produces a lot of early satiety, which is a fancy way of saying that they get full faster, so they're not able to eat as much.

John Horton:

Yeah. Well, you can see where then it would help with losing weight. If you're not hungry as often and you get full faster, that would definitely cut into the calories you're putting in.

Dr. Kathy Zhou:

Yes. I tell patients it's almost like giving yourself a gastric band in a shot, which is perhaps too extreme of an example, but not too off-base.

But there is a third modality by which they work, which I think is really important, which is that they actually have direct metabolic and metabolic inflammatory effects in the body. So they do seem to be able to reduce some degree of insulin resistance and promote a more normal production of insulin from the pancreas, and this can often be very disordered in individuals who are using this medication, especially people with Type 2 diabetes, but also people who are using it for issues like obesity because many of those individuals do have insulin resistance that this medication does correct to a certain degree.

John Horton:

And now, GLP-1s, they started more as a diabetes management sort of tool, correct?

Dr. Kathy Zhou:

They absolutely did. So the first medication to actually come out onto the market was exenatide, and that was back in 2005. I think people sometimes forget that this medication actually has been around, or this class of medication has been around for a long time. Exenatide and most of the medications up until more recent past were approved for Type 2 diabetes. It's only within the last few years, really that we're starting to get the shift into approvals for obesity management.

John Horton:

And how is this medication taken? Is it a pill, is it an injection? What are your options there? For those of us who are probably hoping maybe it is just an easy pill.

Dr. Kathy Zhou:

So barring the fact that there is one medication that is on docket that is a pill that's supposed to be easier to absorb, all of the existing GLPs, minus Rybelsus®, which is semaglutide, come in injectable form. Sorry to burst your bubble.

John Horton:

No, that's fine. I'm not a needle guy.

Dr. Kathy Zhou:

I do tell people that the needles are fairly small. A lot of my patients can't even feel it. For example, Ozempic … comes to mind. A lot of people can't feel these needles that are being used and the devices are actually quite easy. Some of them are auto-injectors, where all you have to do is uncap it, the needle's already preloaded, you put it up to your body and you push a button and it just launches it in. And I do remind people, the more powerful agents such as Ozempic and Mounjaro® for diabetes, or Wegovy, Zepbound® for obesity are once a week. So it's not like you're injecting yourself every single day, luckily.

John Horton:

I was going to ask how often it was. So you're looking mostly once a week. That's all you got to worry about.

Dr. Kathy Zhou:

Unless you're doing Victoza®, Saxenda®, those are, unfortunately, daily shots, but like I said, the needles are small, a lot of people can't even feel them. So it's not too bad.

John Horton:

Now, how long do you have to take them? Is this something that you do for a little bit, you get your weight under control and then you can stop? Or is it once you start, you're just on them?

Dr. Kathy Zhou:

This is really an intriguing question. I think I get a lot of patients in my clinic who say, "Hey, Doc, I want to be on this three, six months and lose some weight, then come off of it." And I have to be like, "Hold your horses. I'm really sorry to break it to you, but this is probably something you're going to need to be on long-term. It's not a short-term medication if you want to continue deriving the benefit." Because what we see is that when people stop these medications, their blood sugars get worse if it's being used for diabetes, their weight often will rebound dramatically off of these medications, and it's because some of the underlying issues that contribute, of course, to diabetes and to excess weight are not issues we're curing with the medication. We're just pushing back on those issues with the medication. So the minute you take the tool away, you get that rebound effect off of it.

John Horton:

Yeah, I was going to say, is the rebound effect just a byproduct of not having the medication or is it more that you maybe return to some of those old habits?

Dr. Kathy Zhou:

It's both.

John Horton:

Or both. Yeah.

Dr. Kathy Zhou:

It really is both because, of course, very quickly, you start to lose the appetite suppression, you lose that early fullness and, consequently, it can be easy to sort of slide back into old habits. But a lot of individuals also report this sort of rebound — like ravenous hunger that happens off of it — almost as if the body is sort of resetting to the native or what our body normally makes in terms of GLP. And so there can be this almost, again, more than just going back to old habits, but this almost rebound hunger that drives this initial weight regain off of the medication.

John Horton:

Now, how effective are GLP-1s when it comes to weight loss? I mean, what can people expect when they start taking this?

Dr. Kathy Zhou:

They can be extraordinarily effective. It sort of depends on which agent you're talking about. For example, liraglutide, when we're talking about Saxenda® for weight loss, you're more in the 5 to 10% weight loss category, but the minute you move up into semaglutide or Wegovy, you're now entering more like 10 to 20%. And then, when you move all the way up to tirzepatide, which is the first and only dual agonist, it's actually a GLP-1 receptor agonist, GIP agonist, you're now talking about 15 to 25% body weight loss, which-

John Horton:

…that's a lot.

Dr. Kathy Zhou:

Considering that bariatric surgery is 30% above, you're starting to approach surgical numbers, which is pretty extraordinary actually.

John Horton:

It is incredible.

And now, for most people, if you're going to start on this, is it something where you need to be classified as having obesity or overweight?

Dr. Kathy Zhou:

So you really qualify based on two routes. One is if you have diabetes, you certainly could qualify and that's probably the easiest route when it comes to insurance.

But the other way, as you mentioned, is to have obesity or to be overweight with comorbidities. Obviously, insurance plans are highly fickle, and each one will vary in terms of what they need to provide coverage if they cover some of the weight loss options at all. That's a big sticking point for us as docs. But usually, those are the criteria.

John Horton:

Because you hear a weight loss drug, and obviously, they work, they're very effective. Do you have people come in and they're like, "Listen, I've got a wedding in six months and I've got 10 pounds that just won't leave. Can I take this for a little bit?"

Dr. Kathy Zhou:

So technically, yes, but if you want to regain all that weight probably quicker than you lost it, that's what you'd be looking at, if you use this for the short-term. And you lose all the additional benefits. These are not just weight loss drugs. I remind people that the reason we're so excited about them is not just the profound impact they have on weight, but because there's now increasing amounts of data that support that they have cardiovascular protective effects, kidney protective effects, liver protective effects — and there's work being done to see if they actually reduce the risk of Alzheimer's and cognitive decline in individuals using them. So they seem to have benefits that even are outside of weight. So while you could take it for three months to lose weight for a wedding, you might want to think about it differently if you're considering your long-term health.

John Horton:

Yeah, it seems like this is more of a long-term thing and it sounds very familiar. We did a podcast on gastric bypass surgery, and I think then, they said it's a lifestyle surgery. This isn't just ... like you said, it's not just weight loss. This is something that you do for your overall health to be able to maybe increase your activity to just live healthier and sometimes, you just need to get rid of some of those pounds in order to get to that point.

Dr. Kathy Zhou:

Absolutely. And again, I just really want to emphasize that point that I think that a lot of focus has been on weight with these medications, but I encourage people to familiarize themselves with additional data around the cardiovascular benefits, reductions in things like heart attacks and strokes, reductions in fatty liver, protection of the kidneys and diabetes. Some of this data now that I'm talking about is in diabetes, but some of it's not.

John Horton:

Definitely. We've covered that topic so often on this podcast. It seems like every health issue eventually comes down to eating healthier and exercising more, and it seems like this fits in that in a way and that it can, like I said, maybe get you to a point where you can do those things a little bit better just by making you said these little hormone modifications.

Dr. Kathy Zhou:

Yeah, absolutely. And I think they give you benefits that are even above and beyond lifestyle. The lifestyle needs to come with this, but there is direct effect of these medications on organs that is becoming increasingly clear to us.

John Horton:

Now, when you say that the GLP-1s, they suppress your appetite a little bit and all that, does it make it then so you won't eat as much? If you do try to eat more, do you just not feel good? Is there a little pushback then?

Dr. Kathy Zhou:

There's 100% a pushback. So what many of these medications do is they literally slow down how quickly your stomach empties out. So you can imagine if you try and eat your normal Cheesecake Factory™ meal on a GLP-1, you're going to rapidly find out that it's not going to fit and you're going to feel pretty nauseous, a lot of reflux, and as many of my patients who are on this medication have indicated to me before, that they know when they didn't eat well on the medication because their body and the medication reminds them. They pay the price in terms of how they're feeling.

John Horton:

And that's just how the medication works because you said it doesn't let as much food just into your stomach, and then, it sounds like and empties slower, so you just fill up quicker and that's it. You got to cut off before you hit seconds.

Dr. Kathy Zhou:

Exactly, exactly. And I will tell you, though, that that effect can attenuate after the first few weeks, which is why sometimes when we talk to patients about side effects on the medications, we do say that the first three to four weeks when that delayed stomach emptying is the worst are some of the most significant side effects in those first three to four weeks. And then you can actually see some attenuation of those side effects in the coming weeks/months.

John Horton:

Now, when you talk about the results, they seem too good to be true. In our skeptical world, that usually makes folks worry. So let's get to one of the big questions that you always hear, and it's: Are these medications safe?

Dr. Kathy Zhou:

I think, right at this moment, they do have a very strong safety profile. As I mentioned, the first of the class, exenatide, came out in 2005, and I think people forget that we've got about 20 years under our belt of experience with these medications. They're not brand-new; they just became popular more recently. And so we haven't seen any strong concerns with regard to safety. Now, there is no doubt in anyone's mind that there have been some adverse events, let's say, on the medication — ranging from the more common side effects, the GI side effects everyone is perhaps more familiar with, all the way to issues as extreme as kidney problems, bowel obstruction, unusual tachycardia, IE, heart racing. So these things do happen. But by and large, for the vast majority of people, they are relatively safe, and side effects that they experience on the medication should go away if they were to stop.

John Horton:

And I have to say, I did not realize these have been around for 20 years, and I take it now, there are people who have been on it for that long and, I guess, are doing fine.

Dr. Kathy Zhou:

Yeah. That population is probably pretty small because, again, they became more popular and obviously, more powerful in more recent years. But many of those individuals are doing well and the data we have, again, supports that when you think about the risk/benefit ratio, which you have to do with any medication, that for a lot of people, that benefit is going to dramatically outweigh the risk of the medication.

John Horton:

Well, and that's always the catch of this. You do have these risks, but then you're also eliminating risks, too, and that's the balance that you have to take into account when you're thinking about starting these up and talking with your healthcare provider.

I want to spend a little bit of more time on some of the potential side effects because we went over them a little bit. Let's start with some of the minor ones, I guess, which I always feel bad calling them “minor.” It seems like the definition of if it's not you, it's minor, but let's go over those ones that are considered a little less intense maybe that somebody might experience.

Dr. Kathy Zhou:

I think your point is very well taken that these are not minor side effects. These are actually side effects that people will stop medication because of. The most common ones are all GI side effects. And if you look at the clinical trials, they occurred in upwards of like 50% of the patients. And if you look at real-world data, it's in like upwards of 70% of patients. So they're extraordinarily common. And I tell patients it's the big five — it's nausea to the point of vomiting, reflux, diarrhea or constipation.

John Horton:

That is not a fun list.

Dr. Kathy Zhou:

Yeah. People get a little wide-eyed when they hear that, but I do remind them that the discontinuation rates, initial discontinuation rates, are nowhere near 50 or 70%, and it's because of something I mentioned earlier, which is the fact that these side effects often are not permanent on the medication. I tell patients that if you can make it through the first three to four weeks on the medication, you often will find that many of these side effects attenuate. Now, do I have patients where it took more on the order of months for the side effects to really dissipate? I do. But often, at that point, you're really making a decision between the benefits you're seeing on the medication, which are sometimes very profound, against your ability to tolerate those GI side effects. And those are by far and away the most common things we see.

John Horton:

Now, those GI side effects, are they just from the medication? I mean, I think we've all taken a pill or something and had it … you get that rumbly tummy a little bit, or is it just getting those hormones coming in and all that little bit of chaos that ensues that causes it?

Dr. Kathy Zhou:

So it is the medication, it's the hormone medication coming in and slowing things down. That's really what it boils down to. So, for example, I often will ask people to intentionally not come into the medication on a very full gut or stomach because the minute the medication goes in and slows everything down, they may end up feeling sicker than they need [inaudible 00:19:19].

John Horton:

That one last big meal before you start.

Dr. Kathy Zhou:

That's right. There's no last hurrah. There's that 24-hour food reduction before that first shot. And so that is something I do really caution people on. It is going to slow things down across the board, and you might be thinking to yourself, Well, the nausea, the reflux, the constipation makes sense if you're telling me things slow down, so what about the diarrhea? That one's not totally understood why the GLPs cause diarrhea. I've spoken with some of my GI colleagues here, and some of them think that actually the diarrhea is what we call “overflow diarrhea,” which is when you get backed up to the extent that essentially, stool is attempting to move around the backup and it becomes liquid in doing so. So all of this is the consequence of the hormones interacting with the gut and causing this general slowdown that seems to occur through the tract.

John Horton:

Is it a little bit of a system reset? Because it seems like you're almost, you're taking this medication and it's reworking your GI system to a point where it's changing how fast everything's moving, how it's processing and it just takes your body a few weeks to adjust to that and get things flowing in the right way.

Dr. Kathy Zhou:

So absolutely, it is a bit of a "system reset." I will tell you there is a rebalancing. So if you've actually looked at studies on what happens to the stomach emptying that I was talking about earlier, which is very delayed initially when a person initially starts on a GLP, where everything is just not moving out. If you wait three to four weeks, it actually looks like it re-normalizes for a large number of individuals, and some of these emptying studies. And so we think that the body does sort of adapt around the medication, which is why we tell people to try and give it that three to four weeks if you can persist, because you could see that many of the symptoms you're having are going to abate significantly.

John Horton:

So hopefully, then, their GI systems dissipate, and it sounds like most people see that reduce after, like you said, three to four weeks.

Let's get, then, into, I guess, the next step of side effects that people might experience.

Dr. Kathy Zhou:

Yeah. So I think that there are rare side effects, things like palpitations, headaches — and I shouldn't even say that headaches are particularly rare, but these things are seen. There's pancreatitis that has been reported, of course, in the clinical trials, and to a certain extent, in the real world as well. And then some theoretical concerns about pancreatic cancer, which are a little bit unclear, let's say.

There's also, of course, a warning on all of these medications about medullary thyroid cancer, which is a really rare inherited, typically, form of thyroid cancer. And these are all things that you could either categorize them as an adverse event, side effect, et cetera, that we have seen on these medications.

Now, I will mention things like palpitations and headaches, having seen this before in patients, one of the bad things about not wanting to eat is that you also sometimes lose the drive to hydrate as well. And so I've seen issues where people become pretty profoundly dehydrated on the medication because they're not feeling great, they forget to hydrate, et cetera. And it's a little unclear if some of the reports of headaches, palpitations, on these medications are actually more so related to issues like dehydration, drops in blood pressure, in addition to any electrolyte abnormalities that may be arising from really a reduction in intake.

John Horton:

All of that makes so much sense because you really are bringing a profound change into your body and how it functions with a really big thing. Because we all … we eat, we drink, that's how we fuel. And you're changing the whole dynamic of that.

Dr. Kathy Zhou:

Yep, absolutely. Absolutely. I do want to emphasize that the pancreatitis … because that does come up in our clinical practice a fair bit, is quite rare, and I have, for example, as well as many colleagues, successfully gotten patients who have history of pancreatitis for other reasons onto these medications. So I will put a plug out there that I do not consider that to be an absolute no-no to a GLP, but it's just something that you have to speak with your doctor about to see if you're still a candidate.

John Horton:

Well, and is this the sort of thing where if you start taking a GLP-1, are you monitored a little bit? Is this stuff tracked just to make sure that you're not going down the wrong road?

Dr. Kathy Zhou:

Absolutely. Just like with any medication, we want to be closely following our patients. I have patients give me updates within the first month. I encourage them to reach out, tell me if they're not feeling well. And I encourage individuals listening to this podcast, if you're on a GLP and you don't feel like you're doing well, that is something your doctor wants to know about. And we do have mitigation techniques for side effects that we're able to employ if we feel that you're really getting a lot of other benefit from the medication and would like to continue it.

John Horton:

Yeah, it sounds like a lot of it, you need to wait out those first couple of weeks, and there's that transition that might be a little tough, but you should come out of it and really then start seeing the results that you want.

Dr. Kathy Zhou:

And now, I don't want to paint this as rainbows and sunshine. There is a group of individuals who will fail this medication because they never do come out of it or the side effects are so severe that they're just, frankly, intolerable. And for those, there is a failure rate, 5 to 10%, with discontinuation right out the gate of patients. And so it is possible that the side effects will be so severe, there is no waiting it out, there is no mitigation, we just have to stop. It's not the right medication for that person. But I would say, more often than not, we are able to get individuals to a place where they are doing OK.

John Horton:

Let's talk about some of the other things that come up. And beyond just those side effects, if you go online, which there's so much fun stuff there, there are a lot of these side effects that come up and they're all Ozempic something, which I know the makers of that just have to love. But let's go over a couple of these body changes that people report and one of them was called “Ozempic butt.” What is that?

Dr. Kathy Zhou:

Yeah, so what gives us the lovely structure of our butts is the presence of not only our muscles in that region but also fat in that region. And what can often happen is when you're on this medication, losing dramatic amounts of weight, that you can lose a lot of fat and potentially even some degree of muscle, if you're not being careful. So you lose a lot of the volume out of the butt. And if it happens very quickly, skin can start to sag. It's going to create that sort of sunken, sagging shape of that we consider to be this Ozempic butt.

So we don't in general, and this applies to all the Ozempic things that are out there, including, for example, Ozempic face. We want people to lose weight in a gradual constrained manner. We don't want people coming back to us after month one, having lost 10% of their body weight in that first month. It's maybe not the best strategy. You want it to be a bit more gradual. You want there to be an effort toward muscle retention, strength training during that time. And if you do that, then the skin and its elasticity has at least some potential of not going into that sagging state that we call something like Ozempic butt.

John Horton:

Ozempic butt, Ozempic face, Ozempic breasts. Sounds like those are all things that are tied to if you lose weight very quickly, you just get, like you said, a little bit of more of a saggy appearance, which probably is not what you were looking for when you decided to start the medication.

Dr. Kathy Zhou:

Correct. And so we advocate for a more kind of … we don't want to say constrained, but more gradual weight loss rather than the cliff effect where a person just suddenly loses too much weight or a tremendous amount of weight just all in the first month or two after starting on the medication. And that's then, additionally, why we advocate for exercise. It's because if you can tone up the muscles that underlie areas, you can avoid some of the sudden loss of volume that is occurring. Now, some of this is unavoidable. For example, some people are just … that's where they're going to lose weight out of their face, out of their butt, breasts, whatever. And, unfortunately, in those cases, we have had situations where people turn to cosmetic procedures to reverse what is happening. Obviously, if you were to regain the weight that you lost, you potentially could mitigate those issues as well — Ozempic butt, face, breasts — but that may not also be the goal of what you want to achieve.

John Horton:

And you guys can kind of... when you're administering the medication, I take it you can do it in dosages that will make that weight loss gradual. I mean, is that something that you're kind of monitoring the whole time to make sure you have a nice, slow and steady weight loss?

Dr. Kathy Zhou:

We don't. And I use the term “slow” a bit cautiously. I would say “steady” weight loss. We don't, again, want that close effect and then no further weight loss. And we do monitor people very closely on it. We want to know how much weight they're losing. We bring them in regularly for visits, and we track all of this, and we want to look … I'm looking at their muscle definition when they come in. And I've had individuals in my office where it's pretty apparent that while they've lost a tremendous amount of body weight, a lot of that weight was lean muscle, muscle mass, and that's exactly what you don't want to happen on these medications, and then you have to maybe back off or even give them a break until they can really get back into the drive of exercise.

John Horton:

And that gets to the whole point you were making a little bit earlier, that it's a lifestyle thing. I mean, it's not ... while these medications are amazing and what they do and they could push you in a certain direction, they don't do everything, there's still something you need to do.

Dr. Kathy Zhou:

I tell patients there is no such thing as a miracle pill, miracle shot, no matter how hard we want to believe in that. True success, long-term success, best outcomes are derived from a combination of taking the medication and appropriate lifestyle change. And again, if you take the medication and you think, “I'm just going to starve myself on it and that's how I'm going to achieve my outcome,” you will lose muscle, significant amounts of muscle while on it, which is once again, not really what we want. And you may be doing your health service in the long run.

John Horton:

Do you do a lot of nutrition counseling with people when they start taking this too just to make sure then if you can't eat as much, you want to make sure that what you do get in is going to give you a lot of bang for the buck there and make sure you're getting all the vitamins and nutrients.

Dr. Kathy Zhou:

Yeah, we certainly try and provide some degree of nutritional counseling. It's probably not as detailed as we would like it to be always, but we do emphasize making sure to eat nutrient-dense foods. So this is avoiding the hyper-processed, just a lot of empty carbohydrates, for example, and really going toward proteins, veggies, things like that, and complex carbs. So you want to make every ounce of food that you eat on these medications count nutritionally for you. Otherwise, you could also end up in a malnourished state, which we have also seen on these medications.

John Horton:

A couple other things that come up I've seen is “Ozempic teeth.” That can't be from rapid weight loss, I'm guessing, because there's not a lot on the teeth. So what is that about?

Dr. Kathy Zhou:

Yeah, so Ozempic teeth is probably not as commonly something we see in the office, but I mentioned the nausea, I mentioned the reflux is one of those big five issues, the vomiting. And so when you have things coming up from below, unfortunately, what that can do to enamel is erode it, and you can get this discoloration of teeth, you can get erosion of enamel, all of that. In addition, if a person is relatively dehydrated, which I also mentioned is a risk on these medications, if they're not paying attention, you can get issues with being more prone to cavities because the mouth is dry, and gingivitis, all these issues. So you do want to take care around hydration. You do want to be mindful of these side effects and alert your doctor if you are indeed going so far as vomiting on the medication, because we don't want things like Ozempic teeth or esophageal erosions to start developing.

John Horton:

Yeah, it sounds like you need to put a stop to that pretty quickly or make some adjustments.

Dr. Kathy Zhou:

Yeah, exactly.

John Horton:

Another thing that really jumped out at me was this thing with “Ozempic personality” or “Ozempic brain.” Sometimes, when you take this medication, does it put you in a little bit of a fog or cause some issues like that?

Dr. Kathy Zhou:

So it is something. Fatigue, that fog is something that we have heard about. It's a little bit hard to exactly place where it's coming from. Certainly, in some cases, I can tell you, it's around issues of malnourishment, dehydration, electrolyte problems. And so when you encourage people to just be a lot more mindful around their nutrition, their hydration status, a lot of that fog and issue lifts. But there also seems to be a group of individuals where that probably isn't the issue. There is actually a direct effect on the brain chemistry somehow, where they are just almost feeling like they're in a brain fog, just chronically fatigued on the medication.

Additionally, it's worth mentioning that one of the things the medication seems to be able to do is sort of divorce our intake and activities from our reward system, our classic dopamine reward system in the brain. And so some people describe a relative feeling of anhedonia, where they no longer derive pleasure, excitement and things that they typically enjoy. And that seems to be something about how the medication is affecting the reward system in the brain. Interestingly enough, it's also being harnessed in addiction medicine because it seems to be able to cut off the pleasure from things like smoking or alcohol use. It actually impacts that significantly. So it's being studied for good in that case, but it can also backfire in other ways that are not so good.

John Horton:

Well, you laid out a lot of these possible things that people might experience. And obviously, that's the trade-off when you take any medication. I mean, there's amazing things that they do, and sometimes, there are these side things that come up, and that's all stuff you need to balance and figure out whether this is the right course for you to try. In speaking of that, when you start talking about taking a GLP-1, is there somebody who's like the ideal candidate? Or what do you look for with somebody to go, "This is something that you would benefit from"?

Dr. Kathy Zhou:

So I think the ideal candidate is, frankly, I think anyone with diabetes would benefit from this medication potentially. There are some caveats there, but I think the benefits in the realm of diabetes are pretty striking in market.

John Horton:

Just anybody with diabetes or if you have diabetes, plus maybe some excess weight?

Dr. Kathy Zhou:

Yeah, so I would say honestly, anyone with Type 2 … I should have qualified that Type 2 to diabetes, which is where it's approved, would certainly probably benefit from this medication, even more so if you have something like, for example, fatty liver or cardiovascular risk or disease that's already there or kidney disease even with these medications potentially could be particularly helpful. And similarly, if you have obesity plus some sort of cardiovascular disease, we now have trials pretty clearly demonstrating that taking these medications dramatically lowers the risk of another cardiovascular event, i.e., heart attack, stroke, cardiovascular death — all of these pretty hard endpoints. So I would think that those are individuals who, in particular, could benefit from this. But I do think that anyone really who has obesity, overweight with comorbidities or Type 2 diabetes, just branching out, most of those individuals probably could have some benefit from this medication.

John Horton:

I guess. And on the flip side, are there people who should definitely avoid taking a GLP-1 where this is a no-go?

Dr. Kathy Zhou:

Yeah, so I think anyone who has an active contraindication for the medication, where they have had an issue, for example, medullary thyroid cancer. If they are actively in a pancreatitis flare, obviously, you wouldn't apply this medication. It's, frankly, contraindicated in those situations. But additionally, I've alluded a few times, or not alluded, just stated, that muscle loss is a huge concern on this medication. So if you have a frail older individual who maybe doesn't have much weight to lose, already has lost muscle mass, and you put them on this medication, you could be asking for trouble. You could create more frailty, more muscle mass loss and make them weaker, less able to sustain any other insults to their health. And unfortunately, this is something I've even witnessed in my own clinic. So you do have to be very careful.

John Horton:

And I want to make sure we emphasize again, too, as you said, GLP-1s are not … they're not magic. I mean, they help you lose weight, but it sounds like there's still a lot that you need to do as part of it, and there's lifestyle changes that need to come with the medication in order for it to really have the impact that you're looking for.

Dr. Kathy Zhou:

100%.

Those numbers I quoted before that went up to 25% weight loss, they were not done through just simply taking a shot. They were accomplished by a significant lifestyle intervention. And again, what we see again and again in clinic and also in the trial is people who really aren't putting any effort into exercise, eating right — they end up with issues like malnourishment on these medications, missing multiple macro or micronutrients, or they end up losing muscle mass. All of which are things you definitely want to try and avoid broadly for your health.

John Horton:

Yeah, it sounds like you really need to buy in to improving yourself when you take these. And if you are somebody dealing with obesity, it sounds like maybe this can maybe get you over that hump a little bit and make it where then you lose a little weight, you are able to exercise a little more by limiting how much you eat, just by tamping that down, it sets you up for success.

Dr. Kathy Zhou:

Absolutely, and I've had a number of individuals who, once you show them that weight loss is possible, because they feel so defeated for so many years, and they are finally losing some weight on these medications, they now are motivated to go to the gym or pick up some resistance training at home, to meal prep and make better choices too deliberately.

John Horton:

It's got to be life-changing for people. If you're somebody, if you're really struggling with obesity and you have a couple, 100 pounds extra on you, I mean, it's hard to do things. And you take a little bit of that weight off, it has to feel so freeing, and that you can go out and do some of these things that maybe you haven't been able to for a long time.

Dr. Kathy Zhou:

It is literally life-changing. And while, again, we've emphasized the point I think enough that these are not somehow miracle drugs at work in the absence of any other effort being applied, I have had patients describe them such in the office that this was life changing as a miracle drug. My favorite is, "Whatever's in this is magical unicorn tears" from one of my patients. I said, "OK, that's a first, but I'll take it. I like it." And that was somebody who really, it had been literally life-changing.

John Horton:

And I'm amazed, the numbers are staggering, just with the percent increase we're seeing in usage. I saw one number where 1 out of 8 people now in the U.S. has maybe used this. So where do you see it going from here? I mean, do you see this trend continuing and it becoming a more common thing to do? And is that going to be a good thing as we move forward?

Dr. Kathy Zhou:

I think it's definitely going to ... it's around to stay, I can tell you that. And I do think it's going to grow in terms of usage. What I will tell you is, year by year, there's increasing niches that this medication is finding use for. Again, some of the more recent data showing an indication, for example, for Wegovy for fatty liver, and that is new and that's new as of this year. Within the last few months, that indication came out. So you're going to see cardiologists using this, and they already are. Hepatologists, liver doctors using this. Kidney doctors, nephrologists using this. So it's going to expand.

I think where the danger is, for all the potential good of these medications, is the appropriate counseling of patients. I think the danger is exactly in what we've been circling, this issue of people thinking that this is some sort of miracle shot. They just take it and they'll be better and fine, do great. And really, it involves quite a bit of counseling monitoring, which many clinicians may or may not have the capacity to do because, for example, if you're a hepatologist, a liver doctor who's never been trained in the use of these medications, you may not know the best way to counsel somebody on it. Although I think that's going to change. But that's going to be a work in progress. That's where I think we need to be careful.

John Horton:

Well, Dr. Zhou, I know when I started this, I said people had a lot of questions. I think we answered a bunch of them. So I appreciate you sharing so much and, really, walking us through everything that goes into taking a GLP-1 and what it can do, what you might see and just the possibilities that are there.

Dr. Kathy Zhou:

No, it's my pleasure. And this was a great conversation and I enjoyed having it, so thank you for having me.

John Horton:

Well, thank you for being here.

Weight loss medications known as GLP-1s have proven to be incredibly effective at taking off pounds. But while the side effects are few, they do exist. So talk with your healthcare provider so you know what you might experience in addition to a skinnier you.

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Speaker 3:

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