What we know (and don’t know) about Ozempic

If you follow the news, you’ve probably heard about a revolutionary new weight loss drug called Ozempic.

The very idea of ​​a new wonder weight loss drug might cause some eye rolling, because it’s the kind of thing we’ve seen before. This is often a drug like ephedra, which was all the rage in the 90s and 2000s. Ephedra did help people lose weight, but it was eventually pulled from shelves due to its links with heart attacks, strokes and seizures.

Ozempic, however, appears to be different, not only pharmacologically but also in terms of its broader potential impact. I’m obviously not a doctor and I’m not an expert on weight loss drugs, but I wanted to know more about what’s going on here and what makes Ozempic unique.

So I invited the journalist Johann Hari on The gray area to talk about his new book, Magic Pill: The Extraordinary Benefits and Worrying Risks of New Slimming Drugs. It’s an eye-opening read, to say the least, in part because Hari experimented with Ozempic himself and spent an enormous amount of time talking to researchers developing and studying these drugs.

Hari and I discuss what we know (and don’t know) about Ozempic and all the ways this drug could change our world. As always, there is a lot more in the full podcast, so listen and follow The gray area on Apple Podcasts, Spotify, Pandora or wherever you find podcasts. New episodes come out every Monday.

This conversation has been edited for length and clarity.

Sean Illing

We have already seen “miracle” drugs for weight loss. What makes Ozempic different?

John Hari

Many things. So the first is that it works on a completely new mechanism. If you eat something now, your gut will produce a hormone called GLP-1, and we now know that this is part of your body’s natural signals telling you that you’ve had enough. But natural GLP-1 only stays in your system for a few minutes. These drugs inject you with an artificial copy of GLP-1, but instead of lasting a few minutes, it stays in your system for an entire week.

It has this weird effect, I’ll never forget the second day I picked it up to research it for the book. I was lying in bed. I woke up and had this really strange feeling, and I couldn’t place in my body what I was feeling. And then I realized I wasn’t hungry.

I woke up and I wasn’t hungry. I don’t remember this happening before. And I went to this restaurant near my house and I ordered what I ordered every day, it was a huge brown bun with lots of chicken and mayonnaise in it. I had three or four mouthfuls and couldn’t eat any more. I felt full.

One of the things that is different is that we know that these medications produce a feeling of fullness that lasts. The feeling of being full and having enough. And we know that they lead to sustained weight loss over a significant period of time.

Sean Illing

How confident are we in some of these first results, which are admittedly quite surprising?

John Hari

Well, there is an extremely high level of confidence that it results in significant weight loss. There have been hundreds of studies involving tens of thousands of people, and that’s just its use for obesity. These drugs have also been used for diabetics and other purposes, which also gives us an idea of ​​the safety risks of these drugs.

Sean Illing

If we’re talking about this hormone that’s not only in your gut but also in your brain, does that mean that this drug could potentially be a general anti-addiction drug, a drug that enhances your ability to control yourself rather than just a weight loss medication?

John Hari

Because it is a hormone produced in your gut, these medications were thought to primarily affect your gut and work by slowing down your gastric system. And it’s true, there is definitely an effect on your gut. But we also know that you have GLP-1 receptors, not only in your gut but also in your brain.

If you give these drugs to rodents and then cut open their brains, you see the drug goes everywhere in their brains. And the neuroscientists I interviewed and the scientific data they produced strongly suggest that these drugs work primarily by changing what you want, by changing your wants and desires.

There’s a huge debate about how this works, and it’s slightly disconcerting to interview leading neuroscientists and say, “Okay, you’re saying it works primarily on my brain.” What is this doing to my brain? And they all say a very erudite view of like, “Ah, we don’t really know. »

There is also widespread debate about the negative and positive effects that could occur. There is some debate over whether it causes depression or even suicidal feelings in a minority of users.

What we know right now is that we have a tremendous amount of incredibly promising evidence in animals. I have interviewed many scientists who have done experiments on this topic. For example, I spoke to Professor Elizabeth Jerlhag, from the University of Gothenburg in Sweden.

What she does is catch a bunch of rats, and they make them drink a lot of alcohol and get them used to it. And rats like to get drunk, they wobble in their little cages. So they give the rats alcohol for long periods of time until their cage resembles a downtown Vegas bar, then they inject their necks with a GLP-1 agonist, the active component of Ozempic and Wegovy.

What they see is a dramatic reduction in the amount of alcohol they consume. It’s usually around 50 percent, and we find that they consume less dopamine when they drink alcohol. They like it less. They want it less. They will put less effort into getting it. It really changes the amount of alcohol they want to consume. Initially it was thought, well, it might just be that these drugs reduce your desire for calories. Obviously alcohol has caloric content, maybe that’s just it.

So other scientists then experimented with drugs that contained no calories. For example, Professor Patricia Grigson of Penn State University induced rats to consume lots of fentanyl and heroin, gave them GLP-1 agonists, and found that they consumed much less. Dr. Gregg Stanwood of Florida State University gave cocaine to mice. When they gave them GLP-1 agonists, they found that the mice consumed significantly less cocaine, again by about 50 percent.

We have a lot of anecdotes, a lot of people I’ve spoken to who started taking Ozempic and saw their addictions go away, but very little human evidence so far. The picture we have is a bit mixed. These medications are known to reduce smoking, but only if combined with a nicotine patch. We know they reduce alcohol consumption, but only for people who aren’t heavy drinkers to begin with. We will know a lot more in the coming years because many trials are underway.

Sean Illing

So the basic causal mechanism here is that the drug turns off the reward centers of the brain?

John Hari

This is very controversial. There are different theories about its effects on the brain. And everyone who gave me a theory said, look, “At this point, it’s speculative. We do not know.

A theory is exactly what you have articulated. You have reward centers in your brain and anything you do that gives you pleasure, whether it’s having sex, eating, meeting a friend, you do it in part because it keeps your reward centers buzzing. And one theory is that I eat more salad and less Big Macs because the Big Mac is significantly less rewarding for me. The gap between the Big Mac and the salad is now much smaller.

However, this theory obviously raises a whole series of concerns. If this dampens my reward system for Big Macs, how do we know that it doesn’t dampen my reward system for writing my next book or having sex or whatever? And, indeed, a safety signal has been raised regarding depression and suicide in a small minority of people using these drugs.

But a different theory is that these drugs stimulate a different system in your brain. As Professor Paul Kenny, chair of the neuroscience department at Mount Sinai, explained to me, in addition to a reward system in your brain, you have something called your satiety system. Satiety is a very important concept in understanding how we got into the obesity crisis and how these medications work. Your satiety is simply the feeling that you have had enough and don’t want any more. Kenny argues that these medications don’t diminish your reward system so much as your satiety system.

Sean Illing

So what happens when you stop taking this medication?

John Hari

We have mixed evidence on this. It may be that a minority of people maintain their weight, but it seems that most people regain most of their weight fairly quickly after they stop gaining it. So it’s not a vacation romance, it’s a marriage for life, or it’s like statins or blood pressure medication. It works as long as you take it, but when you stop taking it, it stops working.

Sean Illing

Are there any other potential downsides that researchers are thinking about?

John Hari

When you talk about the risks, many scientists rightly say, “Actually, we have a lot of evidence here on these drugs.” Diabetics have been taking it for 18 years. So they say, “Look, if they cause horrible effects in the short to medium term, that would have already shown up in diabetics. If it grew horns, diabetics would have horns. And that’s a good point, and it should give us some sense of security.

But also, other scientists are saying that if we’re going to base our confidence on the fact that these drugs are safe for diabetics, then let’s really dig into the data for diabetics.

For example, there’s a brilliant French scientist called Jean-Luc Faillie, and what…