Mark Herz: This is GBH’s Morning Edition. GLP-1s are a family of drugs that you’ve certainly heard of because they include the diabetes drug Ozempic, also known as Wegovy when it’s used for weight loss. And what’s been surprising is not just that these drugs have rapidly turned into blockbusters for the companies that make them, and also worrying insurance companies with their not-insubstantial price tags. With us to help understand all that is Dr. Mehmet Furkan Burak. He’s an obesity-focused physician-scientist at Brigham and Women’s Hospital and Harvard Medical School. He both treats patients and does research. Thanks for joining us.

Dr. Mehmet Furkan Burak: Thanks for having me.

Herz: So as I was saying, the evolution of what we’re finding out about these drugs, what they can do, it seems pretty remarkable. Let’s start from the beginning. Explain for us laypeople GLP-1s as diabetes drugs and then how they became blockbuster weight loss drugs.

Burak: So what we are doing is we are really mimicking the body, and we are using body’s own mechanisms to restore things. And actually, we are trying to bring people to their factory settings. So the GLP-1s are really the part of the meal termination signal, we call it. So when you eat a food, the brain orchestrates a response that starts from your gut and from your other organs and then comes to the brain and basically says, "stop eating, feel full and use this energy." So the GLP-1 was the part of this response system. And then when you get diabetic or if you gain weight or have obesity, your GLP-1 levels goes down. So when we use GLP-1 analogs, they are basically biologic drugs that mimic your own hormones that you get all these metabolic responses all together. So I think what changed is normally this response is, like, seconds. But what we learned, if we use them long-acting and high concentration, they actually can act on brain. Basically, it mimics the response that you do not want to eat or drink anything.

Herz: It’s so interesting to me that you mentioned the brain, because when this started — and correct me if I’m wrong — I believe scientists just thought these were about the gut. And now here you are talking about the brain. And that brings us into how many other conditions. We’re talking about addictions of all kinds, right? What are all the connections here? How is this happening?

Burak: I will basically answer in two ways.

Herz: OK.

Burak: So one way, what we learned is actually the brain is controlling all of those. So brains are very complex neuronal circuits. There’s a network of places that decides whether you’re going to have hunger or you’re going to have satiety. You’re going to use the energy or you’re going to store the energy. And the brain — and there’s one part we call the hypothalamus that collects all the inputs: How much energy you have like immediately available or storage, and decides what you should do. And this is an evolutionary biology for survival. And this is not just one center, but it’s a command center. So when you eat something, it gives you the signal: eat this again. So it’s the same center when you have an addiction, when you have an opioid or when you drink alcohol, it’s the same center that gives you the same message: Get this again. So the order from the gut gives the signal but doesn’t decide what is actually going to happen. So the brain is giving the last orders. So whether you’re going to eat or whether you’re going to stop eating or are you going to search for food, we call it food-seeking behavior, or you’re just going to stop searching for food and basically utilize that energy. So from that angle, we learned that the body always adapts the weight gain but never adapts the weight loss. So it always uses this network to gain it back. So it basically gives you cravings. It increases your food-seeking behaviors, it decreases your energy expenditure. So this comes as a package ...

Herz: OK.

Burak: ... and it’s all connected. So in addition to being a standalone disease, so obesity has this connection. It’s not just a risk factor. It’s actually causal for more than a hundred diseases. But the connection is when you look to their pathogenesis, or what is changing, similar mechanisms are changing. And this is a low-grade inflammation. So when the obesity process starts from energy surplus, all these systems are connected and feeding each other and it puts you in a really bad, vicious cycle — and it only gets worse. But when we treat obesity through the system, that it reverses altogether. And that’s actually the revolution, because all the medications were not really attacking to the system as a whole, it was only try to decrease your energy intake. But these GLP-1s, these new drugs that are biologics, are actually attacking the whole system together and then rescuing all those mechanisms together, which results in improvement in different disease pathologies.

Herz: Well, these start to sound in your description, not just like a revolution in obesity treatment, but a revolution in health, especially for people as they get older. I mean, I’m wondering when I hear the description of all the ways — do you see these drugs as really changing people’s health span, really changing what it looks like in terms of how healthy you are as you get older, or even quite old?

Burak: Totally. I mean, data suggests that. So previously, the problem was weight regain with only diet and exercise or because of this evolutionary biology. So people were feeling guilty. But it was basically the biology is giving you all this cravings and weight regain, which is actually more problematic than obesity. We know that it increases the disease risk. But when these drugs utilize, then you’re not fighting with your brain and you’re able to implement a healthy lifestyle. And we know that the treatments of these diseases would result in, first of all, increased quality of life. But we also know of these diseases will shorten people’s life 5 to 10 years. We think we can put that back and it would basically reflect increased health span and life span too.

Herz: What about, you know, cost has been an issue. Insurance coverage has been an issue. Just in our last 30 seconds, where do you see that going?

Burak: This is probably the biggest challenge now, the access. Because we want to treat the world, and we want to treat obesity as a whole and for long term. This is a chronic disease and it needs to be treated as a chronic disease, not just for six months or one year. And the main challenge is the shortages. And it’s just implemented policies from insurance companies. We still couldn’t do the cost effectiveness analysis in the right way, to show all these benefits and how it would reflect back for the health economy. So currently the insurance systems are trying to figure out: Can they afford this? Because obesity is such a common disease. And if you think about even overweight and obesity, it’s 70% of the population. So it scares the insurance companies for now. From a medical field, we think that this should be accessible to everyone. And we think this is going to be cost-effective if we prevent all these other cardiovascular diseases. But now this is a constant discussion, even in the federal level. So we were very happy to see that even Medicare was taking a step to cover these medications. And we know in Massachusetts we are very proud of MassHealth, that started covering these drugs, weight loss drugs, since January 2024. So we think there will be still some struggle for a couple of years. But after we really see how cost-effective they are, I think insurance companies and the payers will also join us to move forward with these drugs and the new ones in the pipeline.

Herz: Dr. Mehmet Furkan Burak, he’s an obesity focused physician, scientist at Brigham and Women’s Hospital and Harvard Medical School.

Burak: Thanks, Mark. Thanks for having me.

Herz: This is GBH.

Dr. Mehmet Furkan Burak, an obesity-focused physician and scientist at Brigham and Women’s Hospital and Harvard Medical School, said people who have lost weight can feel shame if they later regain that weight.

“People were feeling guilty,” Burak said. “But it was basically the biology is giving you all this cravings and weight regain, which is actually more problematic than obesity. We know that it increases the disease risk.”

Studies have linked weight cycling to cardiovascular disease and diabetes, among other health issues.

That, he said, is where a class of drugs called GLP-1 receptor agonists come in.

GLP-1 receptor agonists include the diabetes drug Ozempic, also known as Wegovy when it’s used for weight loss. The drugs “bring people to their factory settings” by mimicking the GLP-1 hormone, which the body uses as a signal to help the brain decide when to stop eating and when to seek out more food.

“When you eat a food, the brain orchestrates a response that starts from your gut and from your other organs and then comes to the brain and basically says, stop eating, feel full and use this energy,” Burak said.

Often when people gain weight, become obese or become diabetic, their levels of GLP-1 hormones go down, Burak said. The body, he said, adapts to weight gain but doesn’t adapt to weight loss.

“It always uses this network to gain it back. So it basically gives you cravings,” he said. “But when we treat obesity through the system, it reverses altogether. And that’s actually the revolution, because all the [prior] medications were not really attacking to the system as a whole.”

There’s also some research into how people might use GLP-1 analogs to treat substance use disorders. The same brain command center that controls hunger and satiety signals is also involved in addictions, Burak said.

“In the brain, and there’s one part we call the hypothalamus ... it’s a command center,” he said. “So when you eat something, it gives you the signal: Eat this again. So it’s the same center when you have an addiction, when you have an opioid or when you drink alcohol, it’s the same center that gives you the same message: Get this again.”

GLP-1 drugs have rapidly turned into blockbusters for the companies that make them, also worrying insurance companies with their not-insubstantial price tags.

Some hurdles Burak said he’s encountered are medication shortages and insurance companies not covering the medications’ costs.

“This is probably the biggest challenge now, the access,” he said. “We want to treat obesity as a whole and for long term. This is a chronic disease and it needs to be treated as a chronic disease, not just for six months or one year.”