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Fortune
Fortune
Rachel Reiff Ellis

How drugs like Ozempic and Wegovy work for weight loss: 'Food tastes good, but I don't want it'

(Credit: Getty Images)

For the scores of people seeing weight loss success on prescription injectables such as Ozempic, Wegovy, Saxenda, and others, the number on the scale isn’t the only change they’re experiencing. The “food noise” in their brains—the mental distraction of feeling compelled to eat—is also getting quieter.

Robin, 49, from Baltimore, Maryland who is using her first name for privacy, started taking Ozempic in December of 2022 as a preventative measure against diabetes after she showed several signs of insulin resistance. Since then, she’s lost 20 pounds, her blood sugar and blood pressure have both stabilized—and her relationship to food has completely changed.

“I joke that the drug has taken away my last vices,” she says. “Food tastes good, but I don't want it. I don't crave anything, and sometimes I have to force myself to eat. The losing weight is awesome—the drug has definitely improved my numbers, like it was supposed to do. But it makes me a little sad since I enjoy food.”

So how exactly are these drugs hijacking the brain space formerly occupied by the siren song of snacks? By acting like chemical messengers and telling your brain you’re full.

How Ozempic and Wegovy work

Ozempic and Wegovy are in a class of drugs called glucagon-like peptide-1 agonists, or GLP-1 agonists. GLP-1 is a hormone your body makes naturally, one of several that helps regulate your appetite. It also decreases gastric emptying time, meaning food passes through your gut much more slowly, and stimulates and improves the release of insulin, which helps manage your blood sugar.

An agonist is a substance that binds to a receptor (a molecule that receives a signal) on or in a cell and causes the same action as the substance that normally binds to the receptor. In other words, these drugs act like the natural hormone GLP-1 and make your cells’ receptors send the exact same signal they would if they were binding to GLP-1 itself.

“It's essentially hormone replacement for the hunger satiety signaling system that everyone has in their body that is supposed to regulate weight,” says Dr. Lydia Alexander, president elect of the Obesity Medicine Association and chief medical officer for Enara Health. “When weight isn't regulated properly by the body, we have obesity.”

How Ozempic and Wegovy quiet "food noise"

The GLP-1 your body makes gets degraded fairly quickly, but GLP-1 agonists stimulate their receptors for much longer. These receptors are in several different places in your body such as the gut and the liver, but the primary place of action is the brain, says Dr. Nisha Patel, obesity medicine specialist with Sutter Health in San Francisco.

“The body has mechanisms in place that are trying to fight that weight loss,” she says. “They’re saying, ‘No, I don't really like this. I'm going to make you hungrier. I'm going to make it easier for you to want to see food.’ And so the medications are really there to help level the playing field, offset those changes that are happening and make it easier for people to stick with healthy habits.”

How Patel emphasizes it’s not a quick fix—the medication is dosed upward slowly over several months—and for some people, it’s not a fix at all.

“There's a lot of individual variability,” she says. “Not everybody responds as robustly. Some people don't lose weight at all, and in fact, they gain weight. The lifestyle piece of it is still a very important foundation of our care. But medications are a really great tool for our patients to help them improve their health.”

Willpower doesn't treat obesity

Many people are genetically predisposed to a deficiency in or resistance to GLP-1, which means they don’t get the same signals that other people get. It’s much harder for your body to regulate its hunger-satiety system when this is the case. But contrary to some societal messaging, the solution isn’t just to “try harder,” says Alexander.

“It feels as though it should be very simple, that if we just controlled ourselves a bit more and have more willpower, that we would get on top of this,” she says. “But this is a chronic relapsing condition, and our hormones are driving our behavior.”

It’s behavior human bodies have needed to survive, especially 10,000 years ago when food was scarce, says Alexander. But today, they’re sent for the wrong reason, creating a viscous cycle.

“It becomes maddening—you reduce your weight and you’re feeling great about it, but the more you reduce your weight, the further away you get from your weight set point, which increases these signals, driving their behavior to go back and eat. And this is what ends up feeling like a personal failing because you're arm wrestling with your hormones and they're going to win.”

When combined with lifestyle changes, Ozempic and other drugs are highly effective for many people who take them, resulting in around 15% body weight loss on average. It’s a weight not only off their frame, but for many, their mind, too.

“Especially for my patients that have reward-seeking behavior and cravings, they're not feeling like they're constantly having to struggle and fight urges,” says Patel. “It’s pretty liberating.”

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