People say weight-loss drugs 'stop working' — here's what we know about the 'Ozempic plateau' and how to avoid it (2024)

• Many patients report that Ozempic"stops working" at some point.
• This"plateau" may be a kind of developed tolerance, calledtachyphylaxis.
• Some patients up their dose or switch to a stronger drug to move past the plateau.

On Ozempic — a diabetes drug widely used off-label for weight loss — people generally lose about 10% to 15% of their body weight. At least, that's what you'll hear.

The reality is that, like any medication, different bodies react to the active ingredient (semaglutide) quite differently. While some people might lose less than 5% of their body weight on Ozempic, others can surpass 20% or 25% weight loss on the hormone-mimicking shot.

Doctors and scientists are still developing their understanding of why these individual differences exist but, whatever the reason, they do. And, while some people can continue to lose weight on semaglutide until they reach a preset "goal weight," others may struggle to continue making progress on the drug after a few months of use.

This is what many doctors, as well as frustrated patients commiserating online, often call the "Ozempic plateau," though you may have heard it described as a phenomenon where "Ozempic stops working." Here's what's actually going on:

It's important to personalize dosage of weight-loss drugs

Ozempic, developed by Novo Nordisk as a drug to stabilize blood sugar in people with Type 2 diabetes, works on both the belly and the brain. It mimics a hormone that slows down stomach emptying, keeping people fuller longer, and tells the brain to be satisfied with less food.

But not everyone's hormones, stomachs, and brains are wired the same way. As such, people may need to reach for different dosages of the drug to feel it working. For some small portion of people (maybe one in 10 or less), Ozempic just never works at all. But most people will react to the drug in some way, if they're given the proper dosage.

"Very frequently, people — let's say on their first, second dosage — they literally feel nothing. And they start to wonder, what did my doctor give me?" Dr. Steven Batash, a gastric sleeve and weight loss specialist who uses Ozempic in his practice, told Business Insider.

If those initial dosages don't have an effect, a doctor may recommend increasing the dosage again, going up to one milligram.

Suddenly at the proper dose, the patient may go hours and hours between meals, feeling fuller quicker, and satisfied for longer periods of time, Batash explains. "Oh yes, I now feel it!" he says, mimicking the reaction of a hypothetical patient.

Patients may also start to feel more side effects after increasing their dose, like nausea or the occasional vomiting, but this is also a sign the drug is working — at least in the short-term.

Patients may need to up their dose

One way a "plateau" can set in is after several weeks or months of such an effective dosage, according to Batash.

The doctor says this is when some patients discover that "this dosage that used to really do its magic is no longer doing the trick. And I'm starting to revert to my old bad habits, and I find that the hunger suppression is not as effective."

Sometimes, this kind of habituation to a drug — a phenomenon called tachyphylaxis — can be easily solved by upping the person's dose.

But in some cases, patients have already maxed out their dose. For others, upping their prescription does not undo the plateau.

Here, biology and pharmacy have hit their limits, for reasons doctors like Batash still don't quite grasp.

"We can only hypothesize why it doesn't work," Batash said. "It could be that a person's baseline emptying of food is so delayed that you're not going to get an incremental delay from this medication, or the brain has more than one satiety center in the brain, and perhaps the specific satiety center in the brain that Ozempic works on in this particular person may not be super sensitive."

Changing to other, stronger weight-loss drugs may help boost people past their plateaus

Newer, stronger weight-loss drugs are coming to market, which boost multiple hunger hormones, instead of just one. It's possible that someone who doesn't respond strongly to Ozempic, or who plateaus in their weight loss, may feel more of an effect on their body by injecting multiple hormones at once with one of these stronger drugs.

Tirzepatide, for example, is a double agonist, which mimics two hunger hormones. It's marketed as Mounjaro for diabetes and Zepbound for obesity, and people generally lose more weight with it than with semaglutide. Then, there are the yet-to-come "king kong" triple agonist drugs, which are still in clinical trials, but which appear to help people lose on average upwards of 25% of their body weight, rivaling bariatric surgery.

But, no drug is perfect.

"Pretty much all weight loss therapies that have been studied seem to have some kind of plateau," Dr. Sajad Zalzala, chief medical officer at the telemedicine website AgelessRx, said. He believes the limitations of these hormonal drugs just underscore how much we have to learn when it comes to understanding all the complex forces regulating weight and metabolism.

"It highlights the fact that there's nothing miraculous about semaglutide at the end of the day," he said. "I think that's just kind of physiology, that your body's only willing to go so far to shed the weight."

Dr. Peter Billing, who runs a network of Transform Weight Loss centers in the greater Seattle area, says many of his patients will lose around 10 pounds a month on Ozempic, regardless of their size.

"Even someone who needs to lose 30 pounds, they'll lose 10 pounds a month and then they won't lose too much," Billing told Insider. "It just stops. It plateaus."