People are running their own experiments with GLP-1s — with stunning results

**David Greene** (0:03)
This is In Conversation from Apple News. I'm David Greene in for Shumita Basu. Today, the GLP-1 experiment happening in real time.
Millions of people in the US are taking GLP-1 medications right now, an estimated one in eight adults. You probably know these drugs by their brand names, Ozempic, Wegovy, Manjaro and ZepBound, just to name a few. GLP-1 based drugs have been around for years and were originally intended for treating diabetes, but they exploded in use when researchers discovered they could cause significant weight loss and were approved for treating obesity. But people are now reporting improvements across a remarkably wide range of other conditions as well, from addiction to concussion symptoms to fertility, most of which have yet to be formally studied.

**Julia Belluz** (1:00)
The landscape is changing so fast. There's new drugs coming on all the time, and we're learning in real time what these drugs are doing.

**David Greene** (1:07)
That is Julia Belluz. She's a contributing opinion writer to The New York Times and co-author of the book, Food Intelligence, the Science of How Food Both Nourishes and Harms Us. Julia has been reporting on GLP-1s for years, so I wanted to have her on the show to take stock of this moment. What has changed since these drugs became a cultural phenomenon? What the evidence shows and still cannot answer, and what all of it reveals about health science in America?
So you've been covering GLP-1s from the moment that they broke into our consciousness. I wonder what you have seen change. What do you think was the story then, and how would you describe the story of these drugs now?

**Julia Belluz** (1:54)
There have been so many changes. I think one of the fascinating areas that has shifted is this explanation of how the drugs work.
If you go back to the early days when these drugs exploded from being used for diabetes to being used for weight loss and obesity, the general narrative was this idea that this is just a souped up version of a native hormone that we all produce for satiety. So GLP-1 that our body produces in the gut gets released after a meal, it helps us feel full and stop eating, and we just, in these medicines, give people a really high dose of that satiety hormone. Therefore, that makes us feel fuller faster and we stop eating.

**David Greene** (2:36)
We feel satiated, but we don't have to eat anymore.

**Julia Belluz** (2:38)
Exactly, yeah, but it turns out that that's not how these drugs work. We're producing GLP-1 in the gut, but we also produce it in the brain and to a lesser extent the pancreas.
The researchers studying it say, it's not all that important physiologically. These are brain drugs, right?

**David Greene** (2:56)
So the narrative that people fell into, you're saying, is that, oh, this just works with my digestive system to make me feel less hungry. You're saying that's actually largely not true. It has much more to do with brain chemistry and how GLP-1s interact with your brain. That's where we think the weight loss might be coming from and the eating less.

**Julia Belluz** (3:13)
Yes. So a lot of what we know about GLP-1s, we know a lot from clinical trials in humans, but we also know a lot of this modeling of how they work from rodents. And that's true of the appetite system generally. A lot of what we know about appetite comes from animal studies.
And so these studies of rodents where they knock out the receptors in the brain, the GLP-1s stop working for weight loss. And so it seems like they really need to reach into this GLP-1 brain system to start getting that appetite-reducing effect.
I think that the other interesting bit of it in the last few years is we had semaglutide, that was the first approved drug in the form of Wegovy.
And now we have these other dual triple agonists that have come on the market or are coming on the market and you're getting more and more weight loss with these newer GLP-1s. So the numbers now with the newer versions that are in testing, you get close to the levels of weight loss that you get with bariatric surgery only.

**David Greene** (4:09)
I mean, part of what we're seeing now in kind of the health fitness messaging is you should be okay with whatever body type you have. You can have a large body type, small body type and you're still healthy. Wouldn't that contradict the narrative that people are rushing to get these weight loss drugs because they want to get smaller?

**Julia Belluz** (4:26)
So this was, I think, what these drugs revealed. This quest for weight loss is a very long, over a century. And you can trace it back even longer where people are trying to achieve a thinner, a smaller body. They're trying to lose weight. So humans have done jaw wiring. We've taken ingredients from explosives during World War II that sped up the metabolism and caused weight loss. We've taken tapeworms, injected ourselves with elements from horse urine, not to mention all of the fad diets that those of us growing up in the 80s and 90s remember very well and that continue to this day, right? So I think this desire for thinness is not to be underestimated. But we never had a medicine that really worked, that wasn't dangerous. They worked at these levels to help people lose weight.