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Semaglutide, the diabetes medication that's skyrocketed in popularity after it turned out to be a strikingly effective weight loss drug, has its drawbacks — and, per one of the researchers who discovered its underlying mechanism, they can be life-altering.

In interviews with Wired, scientists who pioneered research into glucagon-like peptide 1 (GLP-1), the hormone mimicked by semaglutide — sold as Ozempic, Wegovy, and Rybelsus — reflected on the explosive attention on the drug this year. It's a must-read overall, but particularly interesting was the perspective of Jens Juul Holst, a Danish biomedical researcher who worked on the initial delivery method of GLP-1 imitators, who told the magazine that the drug's effects can be more profound than potential patients might realize.

"What happens is that you lose your appetite and also the pleasure of eating, and so I think there’s a price to be paid when you do that," said Holst, who teaches at the University of Copenhagen. "If you like food, then that pleasure is gone. The craving for food for some people is taken away when they take GLP-1 drugs."

For some people, he pointed out, that's going to be a very big deal — potentially cutting out one of the greatest pleasures in life.

"Once you’ve been on this for a year or two," Holst said, "life is so miserably boring that you can’t stand it any longer and you have to go back to your old life."

It's not exactly a ringing endorsement of the drug, and as the Danish doctor notes, keeping people on GLP-1 medications have been an issue since they first hit the market nearly 20 years ago.

"GLP-1s have been on the market since 2005," Holst said. "Do people stay on them? No, they don’t."

Anyone paying attention to pop medicine will have noticed that semaglutide-based drugs have become uber-popular, with memesdrama, and celebrity endorsements abounding.

The actual science, in contrast, is still playing catch-up. The most basic question — whether the drug leads to positive health outcomes in addition, rather than simply weight loss — is still somewhat hazy, although early signs are promising, with patients showing improved blood pressure, blood glucose, cholesterol, and various other key health markers.

The real gauntlet will be whether those results hold up in a wider population, in the real world, and for longer than a few years. There's also the possibility that we'll find that spending too long on the drug comes with unforeseen health risks; after all, it's only been on the market since 2005, and has only been used for weight loss for a fraction of that period (some animal research has linked semaglutide with cancers, but the connection is hazy and hasn't been demonstrated in human patients).

At the end of the day, all new weight loss drugs are going to fall under the long shadow of previous attempts, which have often been removed from the market after it was discovered that they caused huge health problems instead of making patients healthier.

Will semaglutide and similar drugs be the exception? It's certainly possible. But it's interesting to see one of its creators urging caution — even if the objection is less medical and more sociological.

"I don’t see that a huge part of the population will be put on Wegovy and will stay on Wegovy for the rest of their lives," he said. "I simply don’t see that picture."

More on off-label drug use: Doctors Say a Random Cheap Pill May Actually Reverse Balding

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