Plain English with Derek Thompson

Are GLP-1 Drugs “the Greatest Medical Breakthrough of the 21st Century”?

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Derek Thompson

About the episode

In the past few years, we’ve learned that GLP-1 drugs don’t just help with diabetes or increase people’s feelings of fullness to help them lose weight. They have broad effects on substance abuse and behavior. They even seem to help with otherwise incurable illnesses, like Alzheimer’s and schizophrenia. This month, a team of scientists studying two million patients in the Veterans Affairs medical system found that GLP-1s were associated with “a reduced risk of substance use and psychotic disorders, seizures, neurocognitive disorders (including Alzheimer’s disease and dementia), coagulation disorders (clotting), cardiometabolic disorders (like strokes and heart attacks), infectious illnesses and several respiratory conditions.”

Today’s guest is a coauthor on the paper, Ziyad Al-Aly. He is a physician-scientist at Washington University in St. Louis. We talk about his new paper, the steps he took to make sure his findings were trustworthy, why GLP-1 drugs might work so well, what they’re teaching us about the brain and body, how they’re scrambling our sense of where volition begins and where free will ends, and what scientists should do next with the revelation that these drugs have effects that go far beyond obesity and diabetes.

If you have questions, observations, or ideas for future episodes, email us at PlainEnglish@Spotify.com.

Summary

  • In the following excerpt, Derek talks to Ziyad Al-Aly about the new discoveries related to GLP-1 drugs.

    Derek Thompson: I’m so excited to talk to you about this paper. It’s absolutely fascinating. Before we discuss what you found, set the stage for us because it feels like every week there’s another study—animal study, observational study—showing that, oh, we just learned that GLP-1 drugs do this new thing. It reduces substance use disorders, it reduces Parkinson’s, it reduces Alzheimer’s. Why did you think we needed this paper? What is your paper adding that the existing literature lacks?

    Ziyad Al-Aly: Sure. We saw in the U.S. and actually across the globe that utilization for GLP-1 drugs has actually increased dramatically over the past several years. Then we saw that they’re really actually remarkably effective in treating obesity. But we also saw, as you indicated, a paper here and a paper there showing that “Oh, they may be beneficial in this one thing, or they may be beneficial in this other thing” and realized that nobody had comprehensively looked at all possible health outcomes, really analyzing things from A to Z, leaving no stone unturned.

    So we thought about GLP-1 drugs. That’s kind of like the new territory. You’re landing on a new land, or you’re discovering America for the first [time], and then what you wanted to do, you wanted to map it. You literally want to map it. You want to map the landscape to figure out what these drugs do and don’t do comprehensively, leaving no stone unturned. So we decided to do this paper, and what we essentially did here is that we compared people who started on GLP-1 drugs versus several controls, looking comprehensively at all possible 175 health outcomes.

    Thompson: I actually want to read from the methodology section just briefly because I want people listening to understand how you did what you did so that we can understand how you found what you found. We’ve done a lot of episodes in the last few weeks and months over how science can go wrong, how observational studies, for example, can lead us astray. So I want people to understand what the methodology was here so we can understand why we should trust it.

    It seems to me like you went to Veterans Affairs and you compared veterans on GLP-1 drugs to several different controls: to folks on other type 2 diabetes drugs, like DPP-4 inhibitors, and to a control group of just over a million people in what you call “usual care,” so they weren’t on any kind of newfangled medication. And this way you’re comparing veterans over several years—these individuals were followed, I read, over a median of about four years—you’re comparing outcomes from these distinct groups and seeing, “OK, who had higher or lower rates of Alzheimer’s, higher or lower rates of inflammation?” and so forth.

    Before we go on, what’s important for folks to understand about your methodology that I didn’t mention, and what’s the value of working with a data set like Veterans Affairs?

    Al-Aly: So first of all, this is really a large study, and the value here is that you really have massive amounts of data. More than two million people followed for nearly four years on these GLP-1 drugs. We designed it in a way that we looked at several controls. We weren’t really satisfied by looking at only GLP-1 versus, for example, SGLT2 inhibitors or another diabetes drug called DPP-4 inhibitors. We wanted to literally have a rigorous study examining the effectiveness and risks of GLP-1 drugs versus several controls, including the control that most resembles or actually recapitulates what people do in their real lives. This is really usual care, more than 1.2 million people who are on usual care.

    So [we] compared these massive numbers of people who are on GLP-1 versus these several control groups and followed them for about four years. Then also, importantly, we looked at all possible health outcomes. We didn’t look at only addiction disorders or really at only Alzheimer’s disease or only depressive or psychotic disorders or infections or heart disease or kidney disease. We looked at all of it, everything to try to help us understand what these drugs do and don’t do in people’s bodies.

    Thompson: And I don’t want listeners to feel like I’m hiding the ball here, but just one more question on the methodology. Tell us what’s so useful about using a Veterans Affairs data set. It seems to me like that’s a nice way of controlling the health insurance that people are getting, the way that they’re being able to pay for these drugs. I want to make sure we just stop very briefly on the benefits of doing this study within the VA.

    Al-Aly: Well, this is very important. Thank you for asking this. So the Veterans Affairs system is really the largest integrated health-care system in the United States and provides equitable care to all people who are enrolled in the system, including drug benefits. So a lot of listeners now will say that “Oh, well, these drugs are expensive, and not everybody is on them, and then maybe only rich people are able to access them, or people [who] are really handsomely insured are able to access them, and then it’s not really a surprise that these people have better health outcomes,” right?

    Well, at the VA, everybody equitably, all enrolled veterans have actually equal access to these medications, regardless of their income or other characteristics. That really provides equity and parity and enables us to actually compare people without having to worry that maybe people who are privileged or handsomely insured have access and people who do not have these characteristics don’t have access.

    The other major characteristic is really the volume, is really the large number of individuals. So again, this system is really, the U.S. should celebrate it because it’s really the integrated system that delivers equitable care across the board to all enrollees regardless of their income or socioeconomic status.

    Host: Derek Thompson
    Guest: Ziyad Al-Aly
    Producer: Devon Baroldi

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