For millions, drugs such as Wegovy and Zepbound have felt like a long-awaited breakthrough. These GLP-1 -based medications quiet appetite, make it easier to eat less and often lead to dramatic weight loss. They can also improve blood sugar, cholesterol and blood pressure, all key markers of heart health. But what happens when people stop taking them?

A major new analysis suggests an unsettling answer: much of the weight comes back and often fast, and most of the health benefits fade just as quickly.

British researchers conducted a systematic review and meta-analysis, pooling data from 27 studies involving more than 9,300 people who had taken weight-management medication. It included newer GLP-1 drugs such as semaglutide and tirzepatide, older GLP-1 medications, and other weight-loss drugs including orlistat and the phentermine-topiramate combination. Participants had used the drugs for at least eight weeks and were followed after stopping treatment.

Many people stop GLP-1 drugs because of side effects, cost or abrupt loss of coverage. When the medication stops, its biological effects vanish and people are left without the tools needed to maintain weight loss.

The goal was to measure how fast people regained the weight they'd lost and what happened to their cardiometabolic health once the drugs were discontinued.

On average, people regained about one pound (.4kg) per month after stopping medication. At that pace, body weight was projected to return to pretreatment levels in about 1.7 years. That prediction proved to be true: In randomized trials, weight in the medication group was no different from controls within about 1.4 years after stopping.

Blood sugar, cholesterol, triglycerides and blood pressure all improved while folks were taking the drugs, but then steadily reversed. The researchers estimate that most cardiometabolic markers would return to baseline within about 1.4 years of stopping treatment.

The speed of the rebound surprised even the investigators. “Weight re-gain after a period of weight loss is really common, no matter what approach you take, but what was striking is just how fast it occurred,” lead author Sam West, a postdoctoral researcher at the University of Oxford's Nuffield Department of Primary Care Health Sciences, said in a statement.

To understand what “fast” really means, the researchers compared these results with earlier data on behavioral weight-loss programs that focus on diet and exercise. Those programs typically lead to less weight loss than drugs, but people also regain weight much more slowly.

In this analysis, weight came back about four times faster after stopping medication than after stopping a behavioral program. Body weight returned to what it had been before starting treatment after about 1.7 years for people who had used drugs, compared with nearly four years for those who had relied on lifestyle programs.

Why the difference? GLP-1 drugs work by suppressing hunger and increasing feelings of fullness. When the medication stops, those biological effects vanish and many people are left without the behavioral tools needed to maintain weight loss.

Behavioral weight-loss programs that focus on diet and exercise typically lead to less weight loss than drugs, but people also regain weight much more slowly.

This rebound reflects the nature of obesity itself. In an accompanying opinion piece, West and his co-authors argue that: “Obesity is a chronic relapsing condition, and treatment options need to reflect this reality.”

That perspective has major implications for insurance coverage and access. Many people stop GLP-1 drugs because of side effects, cost or abrupt loss of coverage.

None of this means weight-loss drugs don't work. They do while people take them. Longer-term trials show that continued treatment can sustain weight loss and reduce cardiovascular risk. But this analysis makes clear the short-term use without a long-term strategy is unlikely to produce lasting health gains.

For patients and health systems alike, the message is sobering. When treatment stops, the scale often rebounds.

The study and accompanying opinion piece are published in thebmj.