To lose weight, patients may need to continue taking diet pills, study suggests

A new study confirms that people who take the new injectable drug tilsiparatide (brand name Zepbound) to lose weight need to continue taking it if they want to maintain their weight.

Drugs such as Ozempic, Wegovy, Mounjaro and Zepbound have revolutionized the treatment of obesity, helping people lose significant weight without surgery. With 70% of Americans overweight or obese, there is an outcry to take them. Soaring demand has exceeded manufacturers’ capacity, reshaping the entire nation’s economy and even causing food sellers to worry that the grocery market could shrink as the public eats less.

Although these medications are effective, they can be difficult to take. They are expensive, costing about $1,000 per month to insure. They may also produce significant side effects, such as nausea, vomiting, stomach pain, and more rarely, gastric paralysis, pancreatitis, and intestinal obstruction. In clinical trials, about one-fifth of patients who start taking the active drug do not make it to the end of the study.

So a looming question about their use is whether people can eventually stop taking them, or whether these drugs need to be a lifelong commitment for people who want to maintain weight loss.

A new study published Monday in the medical journal JAMA adds details, showing how people regain weight after they stop taking Zepbound.

Trial test weight regain

The trial, sponsored by Zepbound maker Eli Lilly, followed 670 overweight and obese adults who successfully stayed on the drug for nine months. At this point, half of the people were assigned to continue taking Zepbound, while the other half received placebo injections instead. Neither the researchers nor the study participants knew whether they were getting the active drug or a sham shot.

Everyone in the study was advised to try to cut about 500 calories from their diet and exercise at least 150 minutes a week.

Over the next year, people taking Zepbound continued to lose weight, losing an average of another 6 percent, but eventually their weight stabilized. People who switched to the placebo gained weight. About 9 in 10 people who took tilsiparatide were able to maintain at least 80% of their weight loss, compared with 17% of those in the placebo group.

“If you look at the amount of weight gain, they regained the weight they lost over the course of a year,” said the study’s lead author, Dr. Louis Aronne, an obesity medicine specialist and professor of metabolism. About half.” Research from Weill Cornell Medical College in New York.

Like the drugs Ozempic and Wegovy, tezepatide mimics the gut hormone GLP-1, which lowers blood sugar levels, slows the passage of food through the stomach, and reduces appetite in the brain.

Tirsiparatide also mimics another supplemental hormone called GIP, enhancing its effects. In clinical trials, people who tolerated the drug’s maximum dose (15 milligrams per week) lost an average of about 20 percent of their weight after taking the drug for about a year and a half.

It was originally approved as the drug Mounjaro to help people with type 2 diabetes control their blood sugar. In November, the FDA cleared the obesity drug for sale by its manufacturer, Eli Lilly. When it’s used for weight loss, it’s sold as Zepbound.

Adults were eligible for the study if they had a BMI of 30 or higher, or a BMI of at least 27 and had at least one weight-related health comorbidity (such as high blood pressure). Patients with diabetes were excluded.

Gradually climb back to baseline

From the beginning to the end of the study, subjects taking Zepbound lost an average of 60 pounds in weight and 9 inches in waist circumference compared to when they entered the trial. People who switched to the placebo lost about 22 pounds from their starting weight and still lost more than 3 inches in waist circumference.

Aaron said that in his experience, people who took a placebo were likely to continue to regain the weight they lost.

“How long will it take? I honestly don’t know,” he said.

While this may sound discouraging to those who hope to one day be able to wean themselves off vaccines, there are some bright spots in the data.

Some people who stop taking their medication don’t seem to recover, at least not immediately.

“Not everyone will gain the weight back. That is, one in six people will be able to maintain the weight loss without taking medication,” Aron said.

Aaron said they didn’t have any information about what helped maintainers maintain weight even after they stopped taking the medication, so that’s something future research needs to address.

Beyond that, when the researchers looked at improvements in other aspects of their health, their blood pressure, blood sugar, cholesterol and metabolic improvements all seemed to return to where they were at the start of the study. But they didn’t go beyond their bottom line.

“So, you know, there’s no damage as some people say. They’re no worse off than they were before,” Aaron said. “In some cases, they’re much better off than they were when they started. So there’s some type of ​Preserving benefits under certain circumstances.”

Do the effects of weight loss pills diminish over time?

On the other hand there were some puzzling findings.

About 1 in 10 people who continue taking the drug are unable to maintain at least 80% of their weight loss for a year, so they also begin to regain the weight—even while taking the drug.

Aaron said there is some evidence that the body may compensate for the effects of the drug over time. The hormone leptin, which suppresses hunger, decreases. Ghrelin, the hormone that tells the body it’s time to eat, rises.

“So there are a lot of things that happen that end up stopping you because they think you’re going to starve to death,” he said.

At that time, another medication may need to be added.

“Your body makes this compensation, and when you hit two different places, you get better results,” Aaron said.

Dr. Melanie Jay, director of NYU Langone’s Comprehensive Obesity Program, said that in many ways, the trial results are not surprising.

“Obesity is a chronic disease that cannot be cured by drugs,” said Jay, who was not involved in the study. “For example, in most cases when I give someone a blood pressure medication for high blood pressure, their blood pressure goes down, and I expect that when I take them off the medication, their blood pressure goes back up.”

Jay said most of her patients don’t like the idea of ​​continuing to take medication indefinitely.

She said she’s not aware of any studies that have looked at other strategies to maintain weight lost with these drugs, but they are necessary.

“I know patients and clinicians are experimenting with less frequent dosing strategies to see if they can still maintain weight, but that won’t necessarily be the case in formal studies,” she said.

On the plus side, Jay said, many patients who take these drugs experience such improved health that they are able to wean themselves off other medications for diabetes and high blood pressure.

“So even if they have to take anti-obesity drugs long-term, the net amount of drugs is probably less than if they had never started,” Jay said.

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