When Miracle Weight-Loss Drugs Lose Their Edge
Some people taking GLP-1s experience a return of food noise and start putting pounds back on
Cyndy Dowling struggled with her weight for decades until she found what she thought was a lifelong solution: a monthly injection of one of the popular new weight-loss drugs.
The 69-year-old easily lost 60 pounds in the span of a year and a half. But in early 2025, something changed.
The food noise started creeping back. Her weight began edging up. She had to start “dieting” again. Here’s the twist: She never stopped taking Wegovy, one of the so-called GLP-1 drugs.
A year later, Dowling has regained 10 pounds and is back to relying on protein shakes for some meals, all while continuing her weekly injections. “I’m fighting it as much as I can,” says the retired government employee. “I feel like I’m trying to hold the reins on something I can’t really control.”
We’ve all heard that stopping taking a GLP-1 medication for weight loss—such as semaglutide (marketed as Wegovy) and tirzepatide (sold as Zepbound)—often leads to rapid weight gain, with people returning to baseline in as little as 18 months.
What you might not have heard: For some people, the return of hunger and thoughts of food come back leading to potential weight gain—even while they are still taking the drug, which mimics naturally occurring gut hormones, suppressing appetite and making people feel full faster.
Most obesity doctors say they’ve seen patients in this boat. They say it’s not that the weight-loss medications become less effective. Rather it’s that the body’s biological pressure to regain weight kicks in.
People taking GLP-1s typically lose weight most rapidly in the first four to six months, with weight plateauing nine to 18 months after starting treatment, says Dr. Fatima Stanford, an obesity-medicine physician at Mass General Brigham and associate professor of medicine and pediatrics at Harvard Medical School.
“Obesity is a chronic, relapsing, biologically defended disease,” says Stanford. “The body defends its highest sustained weight. So when weight decreases, compensatory mechanisms intensify. GLP‑1s blunt these signals, but they do not eliminate them entirely.”
It’s not that the medication is less effective, agrees Dr. Amanda Velazquez, director of obesity medicine at the Cedars-Sinai Center for Weight Management and Metabolic Health in Los Angeles. Rather, the body works to counteract the effects of the drug, and that intensifies over time.
The degree of biological pressure varies among people, says Velazquez. Some could start to feel it after a few years on the medication. Others might never experience it at all.
The longer it’s been since you’ve lost weight, the greater the likelihood of the body’s push to get back to the weight it’s used to being at, according to Velazquez. Those who have struggled with obesity longer and have more obesity-related health conditions tend to experience it more, she says.
And the more weight loss, the harder the body will fight to try to put it back on.
Even with bariatric surgery, patients sometimes experience weight regain after two to five years, notes Dr. Caroline Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital in Boston.
GLP-1s override some of the satiety hormones, so people get full more quickly. But there are other pathways counteracting that, so eventually you might start to gain some weight back, says Apovian. “That is your body not wanting you to starve to death.”
Dr. Michelle Hauser, director of obesity medicine at Stanford Lifestyle and Weight Management Center at Stanford Health Care, says she more commonly sees patients on semaglutide who report experiencing weight gain and food noise returning. “It’s pretty frequent,” she says.
Often switching to tirzepatide at a higher dose will resolve the issue, she says, because it’s available at higher doses than semaglutide. The highest available dose of Wegovy is 2.4-milligram injections and that “just isn’t cutting it for a lot of people,” says Hauser.
A spokeswoman for Novo Nordisk, maker of Wegovy, said its clinical trial program showed patients’ weight plateaued about 60 weeks after treatment started.
The company in November filed for regulatory approval of a higher-dose Wegovy injection, at 7.2 milligrams.
Other doctors say it might just be a matter of tirzepatide being more effective overall. On average, people taking tirzepatide lose more weight than those taking semaglutide so it might take them longer to plateau.
What to do if you regain weight while still taking a GLP-1? Doctors advise several things.
First, don’t go off the drug. “I emphasize that stopping the medication is very likely to result in further weight regain,” says Dr. Stanford.
She sees whether a dose adjustment is needed and whether protein intake and resistance training are at high enough levels. She also assesses sleep, stress and other lifestyle factors that can influence diet.
Some doctors like Velazquez say they might add another medication for patients to take in conjunction with the GLP-1. Others encourage patients to ensure they are sticking to a healthy diet and to step up their exercise program.
One important step: Avoid ultraprocessed foods, which are more likely to be eaten in large quantities.
It remains unclear what will happen long-term for people taking GLP-1 medications. It’s possible a subset of people will regain all the weight they lost after a certain amount of time, some doctors say.
Dowling says she’s unsure what she should do now. Should she stop taking Wegovy because it doesn’t seem to be working for her and costs $500 a month? Should she try another weight-loss medication?
“I am so frustrated,” she says. “It is feeling more like another temporary fix to me.”