Roughly one in eight Americans say they are taking a GLP-1 drug — and not just for weight loss. Studies show it can help heart disease, sleep apnea, addiction and even brain health. We speak with one of the lead scientists who discovered this gut hormone on how these drugs actually work in our bodies.

Guests

Jens Juul Holst, professor in the Department of Biomedical Sciences at the University of Copenhagen in Denmark. He’s best known for discovering and developing treatments based on the GLP-1 hormone, which resulted in GLP-1 medicines like Ozempic and Wegovy.

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Transcript of Full Broadcast

The version of our broadcast available at the top of this page and via podcast apps is a condensed version of the full show. You can listen to the full, unedited broadcast here:

Part I  

MEGHNA CHAKRABARTI: Back in 1993, Dr. Jens Juul Holst and his team hooked up patients to a new infusion. These patients had diabetes, and what happened to them was utterly remarkable. The infusion completely normalized their blood glucose levels in just four hours. So Dr. Holst knew he and his team were onto something big, but I’d wager that they couldn’t predict just how big it would become.

Today, you know this discovery by the names of Ozempic, Wegovy, Mounjaro, and the like. They are glucagon-like peptide agonists, or GLP-1s, though technically I should be calling them GLP-1As. But scientific nomenclature aside, the drugs are also being called blockbusters, revolutionary, a miracle. And the superlatives are many.

Consider this, back in 2024, Novo Nordisk, maker of Ozempic, had a market cap larger than the entire economy of Denmark, the company’s home country. Or closer to home, in 2025, a KFF poll found that one in eight Americans said they are currently taking a GLP-1. One in five, or 20% of Americans, said they’d taken the medication at some time.

So when the numbers are that high, it’s not just for diabetes anymore, right? Of course, people are taking GLP-1s for weight loss. There’s also heart disease, liver disease, kidney disease, sleep apnea, addiction, even brain health. But of course, every drug, and especially every blockbuster drug, comes with major questions, such as why do GLP-1s seem to have an impact on such a wide range of ailments?

What are the serious side effects and the serious long-term side effects? Should these drugs be more aggressively regulated in the U.S.? And are they changing our understanding of how the body works? For insights to these important questions, today we’re going straight to the researcher who helped create the drugs, Dr. Jens Juul Holst. I mentioned him right at the top of the show. He’s a professor at the Department of Biomedical Sciences at the University of Copenhagen in Denmark, and he’s won several of the world’s most prestigious awards in science, including the 2020 Warren Alpert Foundation Prize and the 2021 Canada Gairdner International Awards and the 2025 Breakthrough Prize in Life Sciences, and he shared the Alpert Prize, by the way, with other scientists in the United States as well.

He’s also been nominated for the Nobel Prize in Medicine, and he joins us today from Copenhagen in Denmark. Professor Holst, welcome to On Point.

JENS JUUL HOLST: Thank you very much. Thank you very much for asking me to do this.

CHAKRABARTI: I was wondering if you could actually take us back to the very, very beginnings of your interest in gut health.

How did you become drawn into this world of digestion, of diabetes? Tell us that story.

HOLST: I guess I have to emphasize, first of all, that I am a medical doctor, and health and diseases and all that has been on my agenda always for the last 50 years. So I was a young doctor training in surgery and we were having some problems with some of our patients.

Some of them would develop too low blood glucose levels, hypoglycemia, after some of the operations we did, and we were wondering why. It seemed clear that this was because they were producing too much insulin, and that made us concentrate on what is called the incretin effect. That is the stimulation, the amplification of insulin secretion that occurs when you eat rather than if you just raise blood glucose levels.

But at the time, the incretin hormones were not known, so there was something to find out here. And so I concentrated on some cells in the gut that were producing a hormone that is called glucagon, which is also from the pancreas and is doing exactly the opposite as insulin normally.

But it also stimulates insulin secretion so these cells could be interesting. So that was the inspiration. In those days, the diseases that were on people’s mind were not really diabetes, and it was not really obesity, at least not in Europe. It was peptic ulcer disease.

People had gastric ulcers and peptic ulcers. And so our way of thinking was what does the gut do, and how are things in the gut regulated? How is acid secretion regulated in the stomach? So we were looking for hormones with effects on all this, and now also insulin. So this was the ambition.

CHAKRABARTI: And as you said, you were training to be a surgeon at that time.

HOLST: Yes. Yes.

CHAKRABARTI: So endocrinology wasn’t actually the specialty that you were going for. Did you ever finish your surgery training, by the way?

HOLST: No, not really. So and after seven years, it turned out that I had done more research than surgery, so I changed style here, yeah.

CHAKRABARTI: Okay. So you were looking at people who were suffering from peptic ulcers, and you were then studying certain molecules. How did that then lead to the stages of research that finally ended up with this discovery of these GLP-1s?

HOLST: As I said, we had these cells that produced something that looked like glucagon.

So we spent quite a number of time finding out exactly what was in those cells, and it turned out to be a molecule a hormone, if you will, from the gut that is called glicentin, and it contains glucagon in the middle of the structure. But it didn’t really seem to do much, this peptide, so that was, of course, a disappointment.

But what we found out and what we realized was that this was really a part of the precursor of the hormone glucagon. Apparently, this precursor was then produced in the pancreas as well as in the gut. But things were, but it was handled different in the two tissues. And there was only one problem with that very beautiful theory, which was correct, by the way, and that was that proglucagon had to be bigger than what we had found.

So the, this glicentin molecule has 69 amino acids, and the real proglucagon had to be a lot bigger. And that’s why, that’s where the molecular biology came into the field, and there was then particularly an American molecular biologist called Graham Bell, who managed to pull the coding nucleotides of proglucagon out of hamster pancreases and found out that this had to be, this appeared, looked like a peptide of 160 amino acids.

And yes, he found the glicentin part that we had uncovered in one half, but the remaining half was really interesting because there was stretches that looked like glucagon like number one and glucagon like number two, so a pair of glucagon-like stretches of DNA. So this was exactly the signal we needed because then we could try to translate that information into peptides.

We have them synthesized, we produced antibodies, we made radio immunoassays, that’s a measuring method, and we could start finding out what exactly goes on in the body. So we did that.

CHAKRABARTI: Yeah. Okay, so Dr. Holst, can I pause you? I know that you have talked about this for many years now, and I have to say your continuing enthusiasm for the research is really inspiring. But I would like to slow down a little bit for people who aren’t as familiar with all the lab research you’re talking about. And forgive me, but I should have asked this earlier. Let me go back to a very basic question. So in terms of regulating blood sugar in the body, insulin obviously is important because it reduces the amount of blood sugar. Correct me if I say anything that’s wrong. No. And just remind us what glucagon does, because obviously it’s at the center of the research on GLP-1s.

HOLST: Yeah, it’s actually interesting because glucagon does normally the opposite.

So it is a hormone that makes the liver produce glucose. So if blood glucose starts to fall, then the glucagon secretion will be increased and it will act on the liver to make it produce glucose so that normal glucose levels are then restored after that. So that’s what it normally does.

CHAKRABARTI: Okay. So that’s why you need insulin and glucagon hand-in-hand in order to produce the overall regulation.

HOLST: That is true. Yes.

CHAKRABARTI: … Oh no go ahead. Go ahead, please.

HOLST: Oh it’s interesting that in people with diabetes we have either too little insulin or too little insulin action, and usually too much glucagon, and that’s one of the reasons that the blood glucose goes high, that they have too much glucagon at the wrong time.

So that’s why glucagon is very interesting in this connection.

CHAKRABARTI: Understood. Okay, so then you were, you said, as you were saying, you were working on glicentin, but that turned out to not be the answer. It was a precursor to the … go ahead.

HOLST: … to glucagon itself, the interesting thing was really what then happened, that when the full structure of proglucagon was revealed, that there was this glucagon-like, it’s actually interesting that this precursor has not only glucagon, but two additional glucagon-like stretches in it, namely, as I said, a glucagon-like stretch number one, GLP-1, and a glucagon-like stretch number two, GLP-2.

So that was the new observation.

CHAKRABARTI: I should note that even though these GLP-1As, technically, have become such a almost normal part of the American pharmacological options, or actually global in the global pharmacy.

HOLST: That is true.

CHAKRABARTI: We’re talking about research that you did, what, in the 1970s and ’80s, right?

So this story is decades old.

HOLST: Yes, it is. Some things had to go, have their own kind of slow progression because what then happened was that we went to the tissues with our new tools and started to look for what was really produced in these tissues, and that’s how we were able to find GLP-1 in the tissues from the gut, a peptide of 30 amino acids that we could then test on a model we had.

I had developed an isolated perfused, as it is called, pancreas a surviving pancreas that would produce insulin if stimulated, and so we could put this new peptide that we had isolated on this pancreas and see if it produced insulin, and it did. So this was the interesting part, that now all of a sudden, we had something really interesting that had an action.

But this was just the beginning. This was a peptide that would stimulate insulin secretion. Okay, we had that. That was interesting. But then, what else could it do? Nobody would know that. We didn’t know that. We knew that the gut was interesting because we knew that the gut would help stimulate insulin secretion after meals.

Actually, three-quarters of the insulin that comes out after meals … comes from hormones that stimulate insulin secretion.

Part II

CHAKRABARTI: We’re spending some time with Dr. Holst today to try to really understand exactly the mechanism of how these GLP-1 medicines work in order to understand why so many people are taking them for diseases and afflictions far beyond diabetes, which is what the GLP-1s were first intended for.

So Dr. Holst again, please don’t be afraid of slowing down and trying to be, and helping me be sure that we understand the development process here carefully. Because as I said, if it … becomes clear to us as laypeople exactly what’s happening inside the body when these, when people are taking these GLP-1s, then it might make more sense about why, as we’ll talk about later, some people are saying I’m taking it for sleep apnea, and it’s become a miracle drug, which may have little to do with diabetes.

So you talked about that sort of model pancreas that you infused one of the precursors to. That was a pig pancreas, right?

HOLST: Yeah. Yeah.

CHAKRABARTI: Okay. No. And so then what happened, and why was that interesting?

HOLST: So in a way, we had now solved the question of how the gut organizes or stimulates insulin secretion after meal intake.

So this was clearly one of these new incretin hormones that had been looked for so long. So this was an answer to that question, but that didn’t immediately result in any medical progress. It was just a physiological mechanism that had been uncovered.

CHAKRABARTI: Okay, wait, let me just stop you there for a second, Professor, because actually now that you’re saying this, it turns out to be even more remarkable. Even though we knew for a long time that dysregulated insulin production was one of the causes of diabetes, especially, obviously Type 1 and Type 2 diabetes, we didn’t know exactly why there was this dysregulation, so the GLP discovery helped us understand more about how insulin is created in the body.

That’s actually a remarkable discovery in and of itself.

HOLST: Yes. It actually is. It was known that there was this mechanism, but it wasn’t known what hormone would actually do it, and now we came up with a new hormone here that could actually do that. But actually, there was one thing that we noted somewhat later.

That it also inhibited the glucagon secretion that we talked about. And now this is important because if you stimulate insulin secretion, blood glucose will go down. If you inhibit glucagon secretion, you will also make blood glucose go down, because you then inhibit the production of glucose in the body.

So this hormone had a double activity, namely both stimulating insulin secretion and inhibiting glucagon secretion, and that all of a sudden made it interesting because people with diabetes, they have a problem with both insulin and glucagon. So it was beginning, there was a slight glimpse here that it might be possible to use this peptide somehow in the therapy of diabetes.

CHAKRABARTI: That is actually amazing, and I love how scientists talk. That made it interesting. No kidding, right? So but I understand, though, that one of the problems with the GLP-1s that you were using early in your research, though, was that it actually didn’t last long in the human body when infused.

HOLST: Exactly. So that was the problem that then came up. We could demonstrate that this, first, we had to demonstrate that it actually worked in people. But you already mentioned that in the introduction, that it, in fact, this peptide, when it was infused into people with diabetes, that it could normalize their blood glucose levels within a very short time, just four hours.

So this was, of course, extremely important and interesting. And then we started thinking about how can we use this in diabetes therapy. And we looked at what happened after a single injection of GLP-1, and one thing that happened was that there was a very short and very disappointing effect on insulin and glucose.

So why was that? And we had developed measuring systems so we could find out what happened. It turned out that it didn’t live very long. Just for a few minutes in the body, it was eliminated so quickly. And we actually found out why that was. That was because of an enzyme we have in the body that would cut it in two, in pieces, this new hormone.

And it’s an enzyme that is called DPP-4. And we also found out that you could actually inhibit that enzyme and make the peptide survive for a longer period of time. And that became the DPP-4 inhibitors, a medicine that has been used all over the globe for the last 25 years and which has, it’s a wonderful anti-diabetic drug, but it’s not as good as the new ones, I have to say.

But this was a huge development, actually.

CHAKRABARTI: So tell me a little bit more about this because I understand, I think it was Daniel Drucker who brings in the question of how, in terms of how to make it last longer in the human body, Gila monster saliva? I love this story.

HOLST: The Gila monster, it was actually a great inspiration, so the study where we demonstrated the effect in diabetes was from 1993, and that’s what convinced at least some of the pharmaceutical companies, and certainly Novo Nordisk in Denmark, that perhaps it was worthwhile working with this peptide, and that’s why, that’s when they started developing what later became liraglutide or Victoza.

But in the meantime, people in New York John Eng and Raufman had been working with strange animals, strange peptides in strange animals, and they found one, the Gila monster, and from its venom, they could isolate a peptide, which is called exendin number four, and this exendin turned out to be acting on to the, everybody’s surprise, the GLP-1 receptor, which had been cloned in the meantime.

This was interesting, and it seemed to work just like GLP-1. So they developed a small company in California called Amylin Pharmaceuticals, they developed with a bit of help from Eli Lilly, they developed exendin four for diabetes therapy, and it was approved in 2005. And it worked, so that was why it was an important step. It gave back people, or it provided people with some confidence in this principle that you could stimulate the GLP-1 receptor and get a good diabetes therapy out of it.

CHAKRABARTI: Okay. So from the 1970s when you first began your work as a young would-be surgeon, on ulcers to basically in 1993 and then the early 2000s when the GLP-1s were approved for use in diabetes, several decades have gone by, and then just in the, almost seems like with the flip of a switch, the drugs have changed the lives of tens of millions of people.

We asked our own listeners who are on GLP-1s or have been what have the experience has been like, and I just would like to share with you a couple of them right now. This is Peter. He’s in Newton, Massachusetts. He’s had type 2 diabetes for 25 years, and he started taking the GLP-1 medication Mounjaro two years ago.

PETER: It’s a miracle drug, far more effective than insulin for treating type 2 diabetes like ours.

It enables us to eat less and therefore take less insulin, and therefore regulate our blood sugars in a much better fashion.

CHAKRABARTI: Here’s another one. This is Peggy from Kailua, Hawaii. She’s actually an obesity medicine specialist, and she herself has been on a GLP-1 drug for the last two years, and she says she’s lost about 50 pounds and feels great on it.

PEGGY: For me, the disease of obesity has brought with it lots of joint issues, as well as two major cancers, even though I’ve had what I would consider a very healthy lifestyle. I’ve been a vegetarian for 30 years. I was an athlete and have continued to be active, swimming, bicycling, walking, playing volleyball, doing Pilates, doing yoga my whole life, and yet my disease of obesity has not been treated until the last two years.

I’m 66 years old now, and I’m grateful that I live at a time when the biology and pathophysiology of obesity are understood, and we have a treatment that is safe and effective.

CHAKRABARTI: We’ll hear a lot more from other listeners a little later in this hour, Dr. Holst. But what I’m curious about is you have described the physiological mechanism of insulin and glucagon regulation that the GLP-1As act directly on.

So that makes a lot of sense in terms of diabetes control and diabetes management. But as you heard both of those listeners just say, and obviously millions and millions of others say, another impact is A, it slows down digestion in the body, but B, it also just reduces appetite. Do we know how and why it does that?

HOLST: Yeah so again, if I can go a little bit historical here, it was known and suspected that the gut was an important link in the regulation of appetite and food intake. And actually, it was already in 1973 that the first gut hormone was demonstrated to inhibit food intake, in rats though.

But the idea was up then. And, so from then on, people were all the time thinking about this, that there must be hormones from the gut that would be important for regulation of food intake. So eventually we looked at the effects of GLP-1 on food intake, saying that this was a possible effect of it, and yes, it worked.

It did inhibit appetite and food intake in people. And from then on, everybody was looking at this effect. But there’s something important here. When we try to look at the effects on glucose and insulin and doing what we call dose response experiments, where we increase the dose to see how much you can actually obtain with this, then we also found, as we increased the doses, people would start to get sick. And eventually they would vomit.

So there was a limit to what we could do here. And that’s why we had to go slowly with the development of this, and we had to use modest doses to look at the effects of appetite and food intake. And at the early development of these medications, and as you already talked about Exendin-4 or exenatide as it was called Byetta was the trade name also had this problem.

So you had to use rather modest doses, and as a result, the effects on food intake and body weight were also modest. Nothing strong, nothing really impressive. But it was still a great step forward because most other therapies of type 2 diabetes would increase body weight. For instance, insulin and sulfonylureas, the usual treatments of type 2 diabetes.

So it was a progress that it at least didn’t increase body weight, but had a small body weight lowering effect. It was only later in the development that it turned out to be a major effect.

CHAKRABARTI: Yeah. So this is interesting to me because what I’m trying to build towards is a greater understanding as to what the GLP-1s are actually doing that are leading people to, trying it for all sorts of other things.

And this is why weight loss was one of the first things I wanted to talk about. Because, okay, so maybe the fact that the drugs are slowing down digestion is what leads to the reduction in appetite. That makes a lot of sense to me. So is the drug working on the digestive system specifically and only, or in terms of appetite control, is it also working on the brain?

HOLST: Yeah, and so this is what has become apparent that it does actually work on the brain. The hormone we have in the body uses nerves that come from the gut to signal to the brain that we should reduce appetite and food intake. But there are also areas in the brain that you can reach by the circulation, and if you give people an injection of something, a GLP-1 agonist like Wegovy or whatever, you have it in the circulation in a high concentration.

It reaches these receptors in the brain and then signals to important centers in the brain regulating appetite and also reward mechanisms. And these pathways have been worked out quite well in quite detail today. It took some time. Because nobody knew that this was going to happen, of course, you had slowly to develop this concept.

But that is what we know today, that you have these pathways that end up in these appetite-regulating centers and the reward regulation as well.

CHAKRABARTI: So the gut-brain axis essentially, it becomes even more and more important and fascinating with every passing year. Let me just ask you, Professor Holst, as a scientist, this has to be pretty cool, right?

Like you’re finding that this drug initially that was intended to help the many millions of diabetes sufferers is also having an impact on general appetite and reward regulation in the brain. That’s both kind of, that must be exciting and also maybe a little, I don’t know if scary is the right word, but need for caution?

HOLST: So fortunately, the good thing about all of this is that we are talking about a hormone, a normal hormone, a hormone we have in the body, and the way it acts is via receptors that we also have in the body. So this is a natural mechanism of action, and that means that there is a kind of limit to what surprises you’re in for here.

So in principle, you can use pretty low doses of these hormones to elicit the effect, and they are not likely to elicit immediate, at least, toxic effects in the body. So unlike a lot of chemicals, these hormones are likely to do what they’re supposed to do and not to cause too much trouble.

And that’s why you’re a little bit more calm, and you’re a little bit more happy with using a principle that is already existing in the body for therapy.

CHAKRABARTI: Okay, which also means, though, that when you come off of this agonist, that the effect is then pretty rapidly diminished, if not eliminated.

HOLST: Yeah, see, now you’re touching upon a very important and unfortunately, a very serious problem, and that is that when you stop when we’re talking weight loss, of course, if you stop the therapy, the weight will tend to return to where it came from, and that has been observed in numerous studies.

So this is the rule. But that is actually a bad thing.

Part III

CHAKRABARTI: We had just briefly mentioned some of the side effects, and we should go into that in a little bit more detail first. Because we actually heard from several listeners about this.

First of all, here’s Judith. She lives in Connecticut, and she recently started taking Zepbound.

JUDITH: I’ve had some side effects, mostly constipation and brain fog, but they’re manageable with proper nutrition and hydration, which is critical on this drug. But when life gets in the way, I cannot properly hydrate.

I definitely feel it. In general, the day after each shot, I may be constipated, which annoyingly stops the weight loss, and I feel like I have a moderate hangover which may linger for several days. Not really helpful when you’re trying to exercise. I also don’t sleep well that first night. I can understand why so many people stop taking it.

I hope I’m not one of them.

CHAKRABARTI:  And the side effects Judith is describing can also become, as she said, so serious that many people stop taking them, and here’s an example of a serious side effect. This is Wayne from Pullman, Washington. He was on Mounjaro for about a year and lost 50 pounds, but he had this major side effect.

WAYNE: Unfortunately, it caused me to have some gallbladder issues, and I have had my gallbladder removed because of stones. I have yet to go back on GLP-1. I have gained about 20 pounds of weight back.

CHAKRABARTI: So Professor Holst, I wanted to ask you about this because there do seem to be the spectrum of intensity of side effects for these GLP-1 seems to be quite large, and the more and more people who come on it or who go on it and with staying on it for a longer period of time, are you concerned that we may start seeing side effects that are so severe that it would cast some doubt on the efficacy of GLP-1s?

HOLST: I’m following this field very closely, because it’s so important. The immediate problem side effect-wise is, of course, the acute effects associated with nausea and vomiting which is something that people generally or very often observe. That’s about 10, 15% that eventually will drop out because of this.

But the cure for this is patience. That is to be slow on titrating up the doses. With these more powerful compounds that we have today half a year of uptitration may be appropriate, and perhaps even more. So the learning is that you should stay on a low dose as long as you’re comfortable with it.

If you feel bad about increasing the dose, you shouldn’t do it. You should wait because with time, these side effects usually subside. The problem with the gallbladder is a real problem. It’s fortunately rare. It’s probably involved in some of these mechanisms with, I talked about this vagus nerve, and it could be some of these problems that is involved physiologically.

But it is a problem that a small percentage will have an increased incidence of problems with the gallbladder. And that’s something that we will simply have to accept. It’s usually considered less serious than any of the other complications that you have of obesity and diabetes.

So it’s real, but it’s not considered strong enough to make people hesitate to take the medication.

CHAKRABARTI: Yeah. Let’s listen to another listener. This is Bob. He’s in Mashpee, Massachusetts. He was on a GLP-1 for about two years and lost about 40 pounds.

BOB: I did not have any reactions to it, but there is some constipation that continues but is dissipating as I change my diet.

It’s worked quite well, I’m also finding that I don’t have the draw to drink as much as I used to, although I was never a heavy drinker, but it just doesn’t have any real attraction for me anymore.

CHAKRABARTI: Dr. Holst, I know you’ve been following and have heard of other people saying similar things, like not just alcohol, but even just a draw to food or more broadly, other things that used to give people joy in life.

Their sense of attraction to those things has become muted, and some folks have even written in the media of life just becomes so boring that they didn’t want to stay on the drug.

HOLST: So I was appearing on a broadcast together with a colleague from California and as we were about to complete or finish the broadcast, he said, “By the way, I am on two and a half milligrams of tirzepatide myself.”

I said, “What? What?” And this was interesting, but it turned out that as he was, getting into his 60s, he was getting a little bit too bulky, he felt. He didn’t like that. And also, he was drinking a little bit too much red wine. It interfered with his work capacity. So he took two and a half milligrams and solved both problems, and he was very happy now.

So there, you can look at this in different ways, right? It is true. I mentioned that we think that, or we know now, that the GLP-1s interact with what we call the reward system. And the reward system is a mechanism in the brain that makes us happy when we enjoy things, when we enjoy red wine and food and things like that.

And if you take away some of that joy you can probably feel it. It can have a good effect, as in the case of my colleague from California. But of course, if the best thing you have in life is a meal and you take away that pleasure, then maybe it’s not so fun any longer. But I guess this is the price you have to pay. And actually, for a while, I was thinking a lot about how long people were taking the drug, retention after one year, it was usually about 50% or something like that after prescription. And people were wondering why that is.

And the price, of course, was one problem. The side effects that we’ve already talked about is another problem. But then maybe for some people it’s not fun to be on a GLP-1 agonist. At the time, we were afraid that everybody in the world would like to be on a GLP-1, but perhaps there’s a self-limiting effect here.

CHAKRABARTI: … If we could, doctor, and forgive me for interrupting but this seems to be a good moment to then now connect all the dots to why so many people, even if they go off of it after a while, are trying GLP-1s for things that seem to be far from the original metabolic or diabetes related treatments, right?

I made that list at the top. We’ve been seeing people trying it for heart disease, kidney disease. The New York Times had a fabulous article a couple of months ago that featured a woman who had suffered post-concussive brain effects for two years, right? She could barely go outside because the sun was too bright.

She had brain fog for years. She goes on a GLP-1 and within weeks all of those post-concussive brain effects were basically gone. Now, that one really blew my mind, if I could say use that bad pun. But does it have to do with the fact that so many of these body systems, when there’s hyper, like too much inflammation in the body, that starts negatively impacting them, and are GLP-1s, do they have some kind of inflammation regulation?

HOLST: Yeah, so the way I would like to put it is there are two major areas of effects of GLP-1 that we really haven’t talked about, and one is the vascular system. So it seems to have a very good effect on the cells in the blood vessels.

If they’re injured, it helps them healing. If they have inflammation, it helps to reduce the inflammation in the blood cells. So in general, there is a very nice effect, good effect on the vascular system, and of course, the vascular system is common for the entire body, so the kidneys and the liver and the heart and what have you, everything, also the brain.

So if you have a beneficial action on the vascular system, you have a beneficial action throughout the body. The other thing is inflammation. So obesity and diabetes and certain other conditions are also associated with what we call a low-grade inflammation, and that is being accused of being responsible for some of, or a lot of, the problems that we have in metabolic disease, and that’s where GLP-1 has this very pronounced effect on this low-grade inflammation and really puts it down.

It’s really helpful, and again, this is a mechanism that is common for the entire body, so the brain and the heart and the kidneys and the liver and because of these two sets of actions of GLP-1 that are both common to the entire body, you perhaps can understand why it has such beneficial effects.

It’s not a miracle. It is because it has these effects on systems that are common for the whole body.

CHAKRABARTI: Maybe it feels like a miracle because the human body itself is a rather beautifully designed machine but to be clear … are there GLP-1 receptors in the circulatory system?

HOLST: Yes. That is certain, in the blood vessels and in particularly in the lining cells of the small blood vessels, that’s where we have them.

CHAKRABARTI: That seems amazing to me. But unfortunately, we’ve only got about five minutes left. I have so many more questions for you. But just to state the obvious, these drugs have been in global sort of heavy use for, let’s say, 10 to 15 years thus far, which is not very long, especially given the fact that people are using it off-label. And many times, they’re getting it without a doctor’s prescription, right?

We had listeners calling us saying, yes, they’re getting a compounded GLP-1 from China. I suppose you will very enthusiastically recommend more long-term studies to follow whether the long-term consequences of taking these drugs are positive, overall positive or negative.

HOLST: So there’s something that is much more important, and that is to emphasize that the advice that you need to have when you start this therapy because you lose weight, but you also lose lean body mass. And to deal with that, the best thing is to make sure that you get a good diet.

You reduce your food intake so much that you also risk to not get enough protein, not get enough vitamins and all that, not get enough calcium and so forth. So you need, really need to have a look at your diet, what you actually eat when you’re on it, so that it’s sufficient and of a good quality.

And the muscle masses the way to handle that problem is to be physically active. And so what it takes is 30 minutes of exercise every day. A walk, a good brisk walk is good. Good enough. You don’t have to invest in terrible terror instruments and go to an expensive site for exercise.

Physical activity is extremely important, and the other thing that is so very important is whenever you start taking these therapies and do experience a weight loss, you must think about what happens afterwards. Because if you stop the therapy, what happens is that you regain weight, most likely, and that will be fat and not lean body mass.

So you may end up in a place that is worse than what you came from. And that’s why you have a plan, and the doctor needs to have a plan. That’s why it’s so important that you talk to somebody who is knowledgeable about this so that you can deal.

CHAKRABARTI: Yes, okay, so being under doctor supervision.

… And as you said, being patient and going slowly as well. We only have two minutes left, and this is really breaking my heart. I do have so many more questions, but I wanna ask you questions about you, doctor. Just two questions. First of all I’m sitting here in the United States, and any time we talk about health care of any kind, the issue of money comes along.

So I was thinking, you’ve worked with Novo Nordisk on some of your research. Are you an extremely wealthy man now, Dr. Holst?

HOLST: No, not at all. Not at all. I’ve never made a penny on the GLP-1s. I was working as a consultant for Novo Nordisk from 1992 until 2013.

And for a small salary. It was really a small salary. But when we started this research and developed all this, I went around in the streets of Copenhagen, with a sign saying, “Research for the people, not for the profit. Research for the people, not for the profit.”

And we believe that, the ambition was to do good research and really to get something accomplished here, not to make a hell of a lot of money. So this was really not on our mind in those days, and it really hasn’t got into my mind ever since. I’ve had a very nice life with a good salary and all that.

And I get, I was paid as a consultant. But no. That has not been a motive at all, and I haven’t made money out of it. And I don’t have stocks, shares in any of these companies because I would be immediately exposed in the newspapers and all. … I would lose all confidence.

CHAKRABARTI: Yeah. So we have one minute left, and I’m just wondering, what does it feel like to be a researcher who’s been part of what’s genuinely seen as a major breakthrough, almost like a once-in-a-generation kind of breakthrough for-  so many diseases. Like, how does that feel?

HOLST: So first of all, I’m so surprised that this is real. And then secondly, I am so extremely happy that this has been possible because we can tell from the figures that this has really helped many people’s lives, and has prevented a lot of complications, and also has decreased mortality of obesity and diabetes.

And I’m pretty convinced that this will continue. And also, I know that even the WHO these days are thinking about trying to develop GLP-1s for solving the problem of the global obesity. So it’s really amazing. It’s really amazing.

This article was originally published on WBUR.org.