i wanna new drug

The Inevitable Ozempic Post

I’ve been avoiding this one for a while, but in the past week, several people have asked me for my take on the new weight-loss drugs that seem to have taken the world by storm.

So I dug in, reading a few of the tidal wave of recent articles in the media (just how large is Novo Nordisk’s PR budget!?), which ranged from laudatory to bizarre. But the most insightful thing I found was last week’s episode of “A Whole New Level” podcast with Dr. Casey Means. In it, she interviews endocrinologist Dr. Robert Lustig, author of “The Hacking of the American Mind” and “Metabolical,” two books I highly recommend.

So I here are some things I learned from my drivetime listening:

the good…

They work. Ozempic, its brother Wegovy, and newcomer Mounjaro are basically the Tall, Grande and Venti versions of the same drug, a GLP-1 agonist.

GLP-1 agonists are synthetic versions of a hormone called GLP-1 that is found naturally in the digestive system. They have been around for 20 years or so and have been proven successful in helping people with type 2 diabetes to control their blood sugar. They work, Dr. Lustig says, by prompting the pancreas to produce more insulin.

The latest and greatest GLP-1 agonist, semaglutide, came out around 2018, and was found to also cause a bit of weight loss along the way.

“And so some brilliant guy at Novo Nordisk said, ‘Well, if this is causing weight loss, maybe we can give a bigger dose and that will cause MORE weight loss!’” says Lustig. “That resulted in this new branded version called Wegovy.”

It turns out we also have GLP-1 receptors in our brains, and when you flood them with semaglutide (at five times normal levels), the brain gets the message that you’re full. “What we’re doing is we’re basically hijacking the satiety signal,” says Lustig. Over time, this means less eating, which means weight loss — the data shows you can lose up to 16% of your body weight.

…the bad…

But weight loss is not the same as fat loss. Lustig says,

“The data on this is very clear. You put these people in DEXA scanners so you can look at body composition changes, and what you can see on people who are taking Ozempic and Wegovy and Mounjaro is that they are losing equal amounts of muscle and fat.

“Now, the question is, ‘Is that a good thing?’ and the answer is ‘Absolutely not.’

“When you lose both muscle and fat, that’s what starvation does. Your body composition is changing in a way that’s indicative of starvation. If you’re 65 or older, and you lose muscle, you’re gonna die. Sarcopenia, which is a loss of muscle mass, is one of the hallmarks of aging and one of the hallmarks of early death.”

There are other side effects related to nausea, vomiting, constipation, plus rarer, but more serious, cases of pancreatitis and even paralyzed intestinal tracts. In fact, Dr. Lustig says, one-third of patients go off the drug within a few months, not because of the cost, but because of the side effects.

And speaking of the cost, most insurance companies don’t cover these drugs for weight loss, so you can end up shelling out $1200 a month. That’s not just for one or two or six months, though. The fact that patients quickly regain the weight after stopping the drug means that you’ll be paying that vig for life.

…and the downright weird

These drugs were originally developed by researchers from the saliva of the gila monster, which is poisonous to humans. I really have no comment about that. After all, many drugs have their origins in the far-flung corners of nature. But you have to admit, it is kinda weird. I mean, just look at this guy:

Photo by David Clode on Unsplash

But the muscle loss Lustig mentioned gives rise to another, odder side effect: so-called “facial aging.” Lustig says, “When you look at people who have taken Ozempic, you can actually see it because the muscle just sort of dissolves from their face. It’s called ‘Ozempic Face’ for that reason — because they’re losing muscle out of places they shouldn’t be losing muscle.”

The other thing is, no one really knows exactly how these drugs work. Lustig tells his host, “You asked the question, ‘Why does this work?’ and the answer, to this day, is, ‘We don’t really know.’” The increased insulin secretion caused by these drugs should be driving fat gain, he says, but it isn’t. That’s the mystery here, which science has yet to solve.

band-aid

In the end, says Dr. Lustig, this drug is not really addressing the root cause of obesity. It’s just a band-aid.

“You’re bypassing the problem, not fixing the problem. The problem is not that you have GLP-1 deficiency. No one has GLP-1 deficiency. That’s been looked for, and there is not one case.

“You’re not treating a hormone deficiency with a hormone, the way you would be by treating diabetes with insulin; that makes sense because you’re actually fixing the problem. Here, we’re just bypassing the problem.”

Lustig says that these drugs really just replace one problem with another.

“We’re basically telling your brain, ‘Yeah, you’re fat, so starve.’ And an emaciated fat person is not a thin person.”

“It’s basically creating a different problem than the one you had. You had obesity, now you’ve got starvation. How good for you is starvation? Not so good.”

The distinction that Dr. Lustig makes gets to the heart of our culture’s misunderstanding about weight. We often talk about the obesity epidemic, the prevalence of overweight in America. But in fact, what we have is an epidemic of metabolic syndrome — a complex web of interrelated illnesses, of which overweight is one symptom. Solving that problem is much bigger and much harder than simply injecting our brains with lizard saliva, but it’s also a lot more important.