Daniel Drucker, 68, speaks a little Spanish at the BBVA Foundation headquarters in Bilbao, Spain, where he’s about to begin a long round of interviews worthy of a Nobel Prize winner. The Montreal-born researcher is visiting the Basque city to receive the Frontiers of Knowledge Prize.
Drucker jokes that he only knows the important words in Spanish, such as vino (wine) and beer (cerveza). This Canadian endocrinologist is the son of Holocaust survivors and one of the few people who can truly say that they’ve changed the world.
Drucker is currently a professor at the University of Toronto and a researcher at Mount Sinai Hospital in that city. He and Joel Habener, Jens Juul Holst and Svetlana Mojsov have received the award “for their discovery and characterisation of the biologically active form of the hormone glucacon-like peptide (GLP-1).” While the reasoning sounds esoteric — as is the complex science behind it — the products of Drucker’s knowledge are part of popular culture.
The famous medicine Ozempic — a diabetes drug that rose to fame in 2022, when a mysterious wave of thinness swept through Hollywood — has made the Danish firm Novo Nordisk the most valuable company in Europe. The product offers hope for the millions of people who are hungry for esthetics.
Question. What do you think about the hype surrounding the weight-loss drugs that emerged from your research?
Answer. It’s sometimes excessive. When I go out in the world — if I go to the store, if I go to a football match, if I turn the television on — all I see is Ozempic, everywhere. It’s really [present] in popular culture. But I also think it’s an opportunity to show the importance of science and the importance of being able to help people living with obesity that didn’t have good therapies [available] before. But yes, there are abuses and many things that are written [about the drug] that aren’t true.
Q. It’s a great triumph for science. However, at the same time, the fact that these anti-obesity drugs are so successful tells us that there’s a serious social problem at hand.
A. Yeah. I think we don’t understand the obesity epidemic very well. When I was growing up, we were told that the biggest problem in the world was starvation. And today, perhaps that’s been replaced — in many parts of the world — by obesity. Yet, [our genetics] haven’t changed. So, we have to ask ourselves: what has changed about the environment, society, the food we eat, the chemicals that are surrounding us?
We don’t really know exactly what’s [causing] the obesity epidemic. It’s very easy to say ultraprocessed foods or McDonalds or the food industry… and that’s probably contributing to the problem. But I think, at the same time — just as we have very good science [when it comes to] developing drugs — we also need to have very good science [as we try] to understand why we have this obesity epidemic. Because ultimately, we would like to prevent the development of obesity, not just treat obesity.
Q. One aspect of your research is that you’ve shown how people with obesity — or those who are overweight — don’t have a willpower problem. Rather, you’ve demonstrated that their bodies don’t produce the necessary signals to stop their appetite. From a scientific point of view, does it make sense that these drugs are often funded for the sake of treating diabetes, but not for treating obesity?
A. So, I think this is the issue: most countries will approve the medicines for type 2 diabetes and won’t approve the medicines for weight loss. And, for many years, there was a very good discussion about this issue. Some people would [ask], “Why should we approve the medicines for weight loss? What does weight loss do?” Maybe [it makes] you look better. Maybe you buy new clothes, maybe you feel a bit better… but that doesn’t really change your health. [However], about two and a half years ago, we had a very important study called the SELECT trial (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity). These were people without type 2 diabetes, but they were either overweight or [obese] and they had a history of heart disease. They were treated with semaglutide (the active ingredient in Ozempic) for about three and a half years. And what did we see? We saw a 20% reduction in heart attacks [and] strokes, [as well as] a 19% reduction in death. And so, I think that trial [was] very, very important to remind people that obesity itself is a very serious disease, particularly in the population that [also] has heart disease.
[We now have] more evidence demonstrating the real benefits of these medicines beyond weight loss. Kidney disease also seems to be reduced. Now we have [a reduction] in strokes and heart attacks. I think it will become easier to justify the reimbursement. But you know, the insurance companies and the governments are terrified of the cost. If we reimbursed everybody who wanted to lose weight with GLP-1 medicines, there would be no money left for anything else, right?
We’re just starting to generate the evidence that will allow communities to go back to the governments — to go back to the insurance companies — and say, “you know, if you have these risk factors and you have obesity, look at the benefits we can provide with the medicines and [look at] how much money we save by preventing one stroke, by preventing one heart attack, by preventing one person needing dialysis.” This is the kind of work that we have to do as a community to justify the expense.
Daniel Drucker, pictured during an interview with EL PAÍS on Wednesday, June 18, at the BBVA Foundation headquarters in Bilbao, Spain.
Fernando Domingo-Aldama
Q. Are the beneficial effects observed in the kidneys or within the cardiovascular system solely the results of reducing obesity? Or are there other mechanisms at play?
A. In our lab, for many decades, we’ve studied how GLP-1 works. And it’s very clear to us that the benefits of GLP-1 aren’t just [related to] blood sugar control, [nor are they solely related to] weight loss.
[How do we know this? Well,] we can do experiments on animals [who aren’t obese] or don’t have diabetes and we still see the benefits of these drugs [for those living with] heart disease, kidney disease, or liver disease.
[In 2009], we published [research noting] that GLP-1 medicines can reduce heart attacks and improve heart function, even if there’s no diabetes and no weight loss. [And] now, we’re starting to get the clinical evidence. We have very good evidence that the [ability] of these drugs to reduce heart attacks and strokes [doesn’t] require weight loss. [There was] very good evidence in this big trial — the SELECT trial that I talked to you about — [which looked at] more than 17,000 people with obesity and heart disease. [There’s been] a 20% reduction in heart attacks, strokes and death. And the investigators have told us that the people who lost the least amount of weight have the same 20% reduction as the people who lost the most amount of weight.
So, again, weight loss isn’t driving the benefits. A few weeks ago, we had the results of an analysis of another trial in metabolic liver disease from Novo Nordisk, [one which applied] semaglutide. And [we presented the results] at the European Obesity Congress in Spain a few weeks ago. The investigators told us that the [positive outcomes in treating] metabolic liver disease — less fat in the liver, improved liver health and less fibrosis — were independent of weight loss. Even though people lost weight, if you look at the people who didn’t lose weight, they still had the same benefits.
Now, of course, weight loss is fantastic, right? So, I won’t dismiss the benefits of weight loss. Your inflammation goes down. Your joints are better. Every part of your body is healthier if you lose weight. It’s very important to remind ourselves [of that]. But the extra benefits of GLP-1 aren’t just strictly for weight loss.
Q. Sometimes, the benefits of these drugs — and their few side effects — seem too good to be true. There are diabetes drugs such as metformin that could be used to slow aging. Do you think the same effect could be achieved with GLP-1?
A. I will say there’s a big interest in GLP-1 [when it comes to slowing down the] aging [process]. It’s very difficult to do rigorous aging trials, right? Because you can’t study people for 15 or 20 years. [I mean], I guess you could… but it just takes a long time and a lot of money.
[Researchers try] to develop what we call “biomarkers” — indicators of aging in cells and tissues and in the circulation [system] — that they could then measure easily, non-invasively, over a year or two. These biomarkers are going to be predictive of reduction in aging.
But there are also people who we call the “worried well” — healthy, but older people who don’t want to leave this world prematurely — who are already taking metformin, GLP-1, or rapamycin. They’re not going to wait five, 10 or 15 years to find out if [these drugs] work.
The [elderly] community is very interested in GLP-1, both from the weight loss perspective, but also [when it comes to] the reduction of inflammation, which also seems to drive part of aging. The [available scientific research] is still very [limited], but the interest is huge.
Q. I assume that many people in the medical or scientific communities are already taking these drugs, as was the case with metformin.
A. I don’t know the numbers. I suppose Novo Nordisk or Eli Lilly would know how many people have a prescription without having a [diabetes or obesity diagnosis]. They would know. We don’t.
Q. Improvements have also been seen in Ozempic users living with addictions. What does this tell us about the mechanisms at play? How can something that helps with obesity or cardiovascular health also help control urges for other substances?
A. If you ask where in the body do we find the most number of receptors for GLP-1 — which is how it works, it has to talk to a cell through a receptor — the answer is in the brain. There are many regions of the brain that have these receptors.
Why do we eat? [Well], we have to have enough energy to survive. And we’ll often divide people into very simple categories. One category [is made up] of those who eat so they can live. In other words, food isn’t that important, but they know that they need calories and energy to make it to the end of the day. But then, there are other people who love to eat. We say that these people live so that they can eat, because it’s a very important part of their social fabric and they [get] a great deal of pleasure from food.
Many people are in between. If you have 10 friends going out for dinner on Friday night, some friends will say, “I’m not that hungry, but I’ll eat something because we’re going out,” while other friends will say, “that restaurant has my favorite paella. It’s the best in Bilbao. I love it, I can’t wait to eat it.” So, for some of us, there’s clearly a hedonic pleasure from eating, right?
Substance use disorders also have an element of pleasure. Why do we smoke? Why do we use cannabinoids? Why do we drink alcohol [or consume narcotics]? Because the use of those substances sends a pleasure reward signal to the brain.
And what GLP-1 seems to do — whether it’s [being used by] the person who can’t wait to finish the cheesecake, or the person who’s smoking and having cannabinoids, or [consuming] opioids or alcohol — is take down the level of pleasure that we get. It allows people to say, “You know what? Not really that interested anymore in the cheesecake,” or, “I don’t really need to have that cigarette or that extra beer.” There’s nothing exciting about it anymore. Whereas before, there was tremendous enthusiasm, excitement, and brain activity.
That’s a simplistic sort of overview: that there are shared elements of biology that drive our response [to] — and desire [for] — foods and drive our response [to] and desire for some of these other activities and substances. And GLP-1 seems to attenuate the reward pathways.
Now, for substance-use disorders, this science is really just starting. We don’t have any rigorous data yet that says [something like], “if you take the GLP-1 medicines for six months, you’ll reduce smoking or alcohol or cannabis or opioid [use by 50%]. We don’t have that data. We have very, very small studies and we have reports from people who said, “yeah, well, I was taking the medicine for obesity and I wasn’t interested in smoking when I was, I drank fewer beers, etc.” But we don’t yet have rigorous scientific evidence to [confirm whether or not] this will be useful. In other words, will 40% or 50% of people stop smoking [or] stop drinking [if they take GLP-1]? Or will it be 5% or 10% of people?
Q. Do these drugs ease excessive cravings?
A. There’s a very wide spectrum of responses. If you talk to a lot of people, [the answer] can be, “I’m not hungry, but I’m fine,” or “I’m not hungry and I’m just feeling a little tired.” Or, “I’m not hungry. I’m a little tired… and actually, I’m a little sad.” And then, their next response [may be], “I’m depressed and not motivated and don’t really feel like doing anything.”
Most people – I think – are fine. But if you treat enough people, you’ll find [patients] who say, “I don’t feel good [when I’m on] this medicine. It makes me apathetic. It makes me sad. I just don’t like how I’m feeling.”
Q. Do you think — given the safety levels we’ve seen — it would be reasonable to prescribe these types of medications to people who aren’t sick, or who we don’t define as such?
A. You mean just for weight loss alone?
Q. Yes. Or perhaps also to regulate cravings in people who feel like they’re consuming too much of something.
A. I’m a scientist, right? [Hence], I’m very conservative. And I always remind people that we don’t have data on many different types of [patients] to understand [what’s safe] and [what are the benefits].
If somebody [asked] me if it’s safe to treat people who don’t have type 2 diabetes — [those who] aren’t living with obesity, but want to lose [22 pounds] because they would feel better — I would say, “Let’s do a clinical trial. Let’s take 5,000 people with a BMI of 25 to 28, treat them for six or 12 months and [determine] if the [balance of] risks and benefits [is] favorable.
I’m not particularly worried. We’ve had these drugs for 20 years in the clinic. They’re not new drugs. But, as a scientist, I would always say you need to study the population that you intend to treat and not just assume that the benefits will be fine and that there won’t be any side effects.
I’m very conservative. I don’t sell the drugs. I study the drugs.
Q. Do you see a risk that, in 20 or 30 years, we’ll simply stop trying to prevent obesity or diabetes, and all the associated problems, and instead opt for taking drugs and forgetting about the root causes?
A. I hope not. I think that would be a lost opportunity. I don’t think that we should approach the problem of obesity only from the treatment side. We should always be very active in trying to understand why the problems develop. Because what if the solution is very simple, very easy and very inexpensive? That’s much better than [billions of people] taking very expensive drugs for many years.
As a scientist, I would never suggest that we stop researching the causes of obesity. I think that’s an extremely important activity that we should always focus on.
Sign up for our weekly newsletter to get more English-language news coverage from EL PAÍS USA Edition