Can GLP-1 Weight Loss Drugs Protect the Heart? with Dr. David Majure

Faith: Welcome to Health Matters, your weekly dose of the latest in health and wellness from NewYork-Presbyterian. I’m Faith Salie.

Many of us have heard about the weight-loss effects of GLP-1 medications like Ozempic or Wegovy. But earlier this year, the FDA approved a new use for Wegovy — as a treatment to reduce the risk of cardiovascular death, heart attack, and stroke in certain adults.

So why do these drugs support the heart and how is that related to weight loss?

To explore the complex connections among weight, cardiovascular health, and inflammation we talked with Dr. David Majure, Medical Director of the Heart Transplant Service with NewYork-Presbyterian and Weill Cornell Medicine.

He described how these medications work, who can benefit from them, and the long term implications of taking them, not just for the heart, and weight, but for the whole body.

​Faith: Dr. David Majure. It is such a pleasure to have you back on Health Matters.

Dr. David Majure: Thank you, Faith, for having me. Real pleasure.

Faith: We are going to talk about something that’s really important. And I think also perhaps misunderstood. Let’s get really basic. What is a semaglutide and what drugs is it in?

Dr. David Majure: Ozempic, which is semaglutide, which is also Wegovy, is a GLP-1 receptor agonist. An agonist is something that stimulates something. GLP-1 is a naturally occurring hormone, um, that is released primarily in our gut in response to food, all sorts of food, but in particular, glucose. And that tells the body to do all sorts of things. It slows down the gut. It slows down movement of food through the gut. It leads your brain to feeling content with the amount of food that you have.

In a sense, it’s a hormone that basically tells your body that you’ve had enough. You don’t need to eat anymore. Initially this concept of these medicines was for diabetes, but people had a sense at the same time that it would impact weight because they knew that not only did it impact the secretion of insulin, but it also led to slowing down the gut, and there was some knowledge that it had something to do with centers in the brain and the hypothalamus that controlled appetite. And so there was a hint of that early on, but it wasn’t until semaglutide and the tremendous weight loss that was seen with semaglutide that this really took off.

Faith: So these drugs were developed for treating diabetes.

Dr. David Majure: Yea.

Faith: Can you say more about how they work in treating diabetes specifically?

Dr. David Majure: Type 2 diabetes is largely a problem related to both insulin secretion and sensitivity of the tissues to insulin. And most of the drugs that we use, either you’re giving insulin directly, or they stimulate the pancreas to make more or you have medicines that act somewhere along that process that basically help the body produce more insulin to, react to the glucose that’s present.

So glucose control is a big part of this. And in the diabetes trials, you absolutely saw that diabetes control was improved, but the real benefit is far more than that, because most of the medicines that we have had for diabetes up to this point didn’t actually cause reductions in events of cardiovascular disease. So things like heart attacks, myocardial infarction, strokes, death due to these things, most of the drugs that we had in the past didn’t actually do anything against those outcomes that we would like to prevent. So this class of medicines under this GLP-1 receptor agonist category, they not only improve diabetes, but they also lead to people not dying as frequently because of heart attacks and strokes.

Faith: So you are really focused on the heart health effects of these drugs. What sort of things are we seeing about the relationship between these drugs and cardiovascular health?

Dr. David Majure: It became very clear in the diabetes trials that people treated with these medications, even the earlier formulations had reduction in cardiovascular events. So they weren’t having as many heart attacks, they weren’t having as many strokes, peripheral arterial disease was not progressing as rapidly, and they weren’t dying. Then if you step away from the diabetes, because you say, well, people with diabetes, they’re a higher risk group of people. So what if we just look at people who don’t have diabetes, but they’re still overweight or obese?

And maybe they’ve already had a cardiovascular event. Maybe they’ve already had a heart attack. So with the use of semaglutide in this case, the reduction in further events is and death due to cardiovascular causes around 20%, which is usually considered to be a very significant decrease in events. Multiply that over across the society as a whole, you’re talking about significant reductions in these fatal events.

To really think about this right, it’s the whole body, it’s the whole system, and we really shouldn’t separate one from the other. Which is also a beauty of this therapy is that by treating people, we’re not talking about just reducing the cardiovascular events, even though that’s what we’ve demonstrated in a lot of the trials, but we’re talking about even trying to reduce the risk of cancers that maybe won’t even develop from years to come. So it really, it really is a holistic thing. Lower back pain, knee pain, ankle pain. These are the slow burdens that people experience slowly over time.

Faith: Why do weight loss effects happen with this class of drugs?

Dr. David Majure: Well, the full story we probably don’t completely understand, but the desire to eat decreases. And your body is told it’s had enough by slowing down the gut, by handling the sugar that’s already being delivered into the body, and by telling the brain, the part of the brain that’s involved in hunger, that you don’t need to be so hungry anymore.

And this is where it gets really fascinating is that we see that in people that are overweight or have diabetes that the amount of native GLP-1 in their blood is, on average, a little bit less than people who aren’t. And that as people lose weight, the amount of naturally produced GLP-1 in their blood starts to increase.

And so there’s evidence that there’s perhaps a dysregulation in GLP-1 in people who are overweight already. And you probably hear this anecdotally, people that are obese in particular, oftentimes they just don’t feel sated. This hormone is really cluing us in to part of that process and how hormones, proteins floating around in our body, can influence the choices we make and the behaviors that we have.

Faith: So for patients on these medications, do they ever run the risk of not eating enough?

Dr. David Majure: So that is one that I actually worry about a little bit. So let’s just say, if you lose 20 percent of your weight with one of these more potent therapies, not all of that is fat tissue that’s being lost. And in some situations, about 40 percent of it might even be lean body mass.

Faith: Meaning you’re losing muscle, right?

Dr. David Majure: You’re losing muscle. Right. And where I think this in particular can be a problem is that if people are taking the medicine but aren’t actually obese or aren’t actually overweight, then you can get into a potential problem where you’re just not eating enough to maintain a good state of health. And this is where I think people can get really in trouble, especially if they’re just worried about wanting to be thinner. In that situation, potentially it could lose protein.

And unfortunately for now, these medicines are probably something that people would have to take chronically. When you stop them, you will gain back the weight. It will come back. If a person cycles with these medicines, if people are taking them and lose both fat and muscle and then stop the medicine, they’re probably more likely to gain back more fat than they gain back muscle. And if they continue to do this, the so-called weight cycling, you could get in a situation where you ultimately are gaining back a lot of fat tissue and actually losing muscle. And so I think it’s really important that people be careful with that.

In people who are overweight or obese and have diabetes or people who are obese or overweight and have cardiovascular problems, like they’ve already had a heart attack, they’ve already had a stroke, they’re at risk for further events. Regardless of the type of weight loss, it’s very clear that those people do very well with these medications in terms of avoiding future events.

When we talk about obesity, we’re really talking about excess fat tissue. And I want to just break that down real fast. Typically speaking, you hear about BMI or body mass index. And that’s a very crude measure of how your height and your weight are related to each other. And it’s useful, and it can help to discriminate between people that are overweight or even underweight, which is also, can be a problem, of course. But it’s a crude analysis.

One of the groups of people that is missed with BMI are older people who have lost a lot of muscle but have gained a lot of abdominal fat. And so they might have a toxic level of adipose tissue around their organs, but their BMI will actually just put them in the overweight range or even in the normal weight range. And I think we need to be particularly careful with these medicines in those people who already have such low amount of muscle, because you might end up in a situation where you’re losing fat, but they’re already so malnourished, nutritionally deplete, that they potentially could have problems.

People that have a lot of muscle mass will have a high BMI without having a lot of fat content. And so better measures and measures that are starting to be taken on more popularly in the clinic space are really taking into consideration, What’s the circumference of the waist? What’s the circumference of the hips? And how does that relate to height? And that makes sense. The bigger somebody’s belly is relative to how tall they are is probably a better indicator of the amount of excess adipose tissue.

But we’re also talking about adipose tissue that’s around the organs themselves. This isn’t fat that’s just under the skin. It’s fat that’s wrapped around the organs, and that fat that is wrapped around the organs has profound negative impacts on the functioning of the organs themselves.

Faith: Is that fat also part of what we understand as inflammation?

Dr. David Majure: Absolutely. So remember, fat is a normal part of our body. We all have fat. We all need fat. It’s part of the way that we store energy. Too much fat, though, can produce various types of inflammation. It can do that by a variety of ways, but one of them is that the immune system itself appears to be activated, and so you get more dangerous inflammatory T cells, for example, in the tissues when there’s excess fat.

In addition, the more fat tissue that’s around the organs, the harder it is for oxygen to actually even get into those tissues. All of this has a negative impact on the surrounding organs, whether that be the heart in this particular case, like we’re talking about, but also the liver, the gut itself. All the organs can be impacted by this.

If we tried to look just at the fat around the heart, when we do echocardiograms, the sonograms of the heart, where we, where we look at the heart with ultrasound, you can actually see fat around the heart. We call it the epicardial fat pad. It’s the fat pad that’s just right under the sternum and it’s not noticeable in everybody unless you have an excess of fat tissue. So the, a group out of Los Angeles, I believe, demonstrated a reduction in the size and density of that fat pad in front of the heart with these therapies.

Other people have shown that the size of the left atrium, that’s the chamber that the lungs drain into, the left atrium of the heart in people that are obese, it oftentimes gets very large and they develop this problem where the heart doesn’t relax well. And with this therapy, we’ve seen that the actual size of the heart improves. The left atrium starts to go back to a normal size. So it’s not just that we’re seeing, once again, the reduction in fat, we’re seeing meaningful changes in the structure of the heart itself and in the tissue around it.

Faith: So how often do you actually recommend these drugs as treatment for your patients?

Dr. David Majure: You know, I’ll tell you, before semaglutide and before tirzepatide, because we’re using both of these right now, I not infrequently would send patients for bariatric surgery, for gastric sleeve in particular. And the reason is because people could lose enormous amounts of weight, 20 to 30 percent of their weight, with bariatric surgery.

In some situations, these were patients who needed a heart transplant, but we wouldn’t do it because they weighed too much and their risk of poor outcomes was so high. So we would send them to the surgery for that purpose. Now we have this medicine that potentially can achieve the same goals. It is a chronic, probably lifelong medication. It’s a huge commitment. And the important thing is that you match the right therapy with the right person. A person should not be on a therapy for which they will not derive a great benefit. Especially if it’s very costly, especially if there’s potential harm.

So for instance, with these medicines, when you start them, There’s a risk of nausea and vomiting, constipation that can really impact a person’s quality of life. It is very dose dependent, and it’s dependent on how long you’ve been at a particular interval of the drug. And I’ve already mentioned the risk if you stop taking the medicine, which is that you will very likely gain back the weight right away. I’ve also mentioned that it is extremely important to avoid the muscle loss.

And so what I do, and mind you, I’m only prescribing these in people that are overweight or obese and because of the patients that I take care of, they have cardiovascular problems and or diabetes, is I really point out to them that we have to be careful with them making sure that they’re getting adequate protein in their diet.

Faith: These impacts on heart health are not only because of the drug’s impact on body fat?

Dr. David Majure: That is correct. Yeah, it’s part of it, but it’s not the whole story. And so, it’s probably somewhat inflammation, somewhat weight loss, somewhat related to improvements in glucose metabolism. Perhaps in terms of things that we don’t fully understand, but it’s the whole, it’s all of that together that’s probably improving the situation that people find themselves in.

Faith: Dr. Majure, it’s been such a pleasure to have you shed light on all of this. Thank you so much.

Dr. David Majure: Thank you, Faith.

Faith: Our many thanks to Dr. David Majure.

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